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You’ve already learned how the brain offers an instantaneous coordination between organs. Neurological coordination can be swift but it is also short-lived. Because the nerve fibers don’t innervate all the cells in the body, and the cellular functions have to be controlled continuously; specific coordination and integration must be made available. This is accomplished by hormones. Both the neural and endocrine system together control and coordinate the physiological functions of the body. 22.1 ENDOCRINE GLANDS and HORMONES The endocrine glands do not have ducts and , therefore, are referred to as glands that are not ductless. Their hormones are the substances they release. The classic notion of hormone as being a chemical created by endocrine glands that is released into bloodstreams and then transported to a distantly situated target organ is now a scientific definitions like Hormones are chemicals that are not nutritional which function as intercellular messengers and are created in tiny quantities. Best JEE coaching in Guwahati.

The definition of hormones has been updated to include many new molecules that are in along with the hormones produced by the glands of the endocrine system that are organised. Invertebrates have systems of endocrine, with only a very few hormones while a huge amount of chemical substances act as hormones, and are responsible for coordination within vertebrates. Our endocrine system can be described in this. CHAPTER 22: CHEMICAL COORDINATION AND INTERGRATION 22 22.1 Endocrine Glands and Hormones 22.2 Human Endocrine System 22.3 Hormones in the Gastrointestinal Tract, Kidney and Heart 22.3 Heart Kidney, Heart, as well as Gastrointestinal Tract 22.4 Mechanism of hormone action 2015-16(19/01/2015) Chemical Coordination and Integration 331 22.2 Human Endocrine System glands of the endocrine system and hormone-producing diffused cells and tissues located in different areas of our bodies form our endocrine system. 

Pituitary, pineal adrenal, pancreas parathyroid, thymus, and gonads (testis for males, and ovary for females) are the endocrine organs that are organized organs of our bodies (Figure 22.1). Alongside these several other organs such as the e.g. digestive tract kidney, liver and heart also release hormones. An overview of the structure and function of the major glands of endocrine and the hypothalamus in the human body are described in the next sections. 22.2.1 2. The Hypothalamus As you may have guessed that hypothalamus is hypothalamus is the central part of the diencephalon brain forebrain (Figure 22.1) which is why controls a variety of functions in the body. It is home to several types of neurosecretory cells, known as nuclei, which make hormones. The hormones control the synthesis and release of pituitary hormones. But, the hormones created by the hypothalamus comprise two kinds, the hormones that release (which encourage the release pituitary hormones) and inhibiting hormones (which block the release of pituitary hormones). Best JEE coaching in Guwahati.

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For instance, a hypothalamic hormone known as Gonadotrophin release hormone (GnRH) increases pituitary synthesis process and releases gonadotrophins. In contrast the hypothalamus’ somatostatin blocks the release of grow hormones from pituitary. These hormones originate from hypothalamic nerves, move through axons before being released from nerve endpoints. These hormones enter the pituitary gland through the portal circulatory system, and regulate the activities of the anterior pituitary gland. The posterior pituitary is subject to the direct neurologic control by the hypothalamus (Figure 22.2). Figure 22.1 Placement of the glands of the endocrine system testis (in male) Ovary (in female) Adrenal Pancreas Thyroid and Parathyroid Thymus Pituitary of the Pineal Hypothalamus 2015-16(19/01/2015) 332 BIOLOGY 22.2.2 The Pituitary Gland The pituitary gland is situated within a bony cavity known as sella tursica.Best JEE coaching in Guwahati.

It is connected to the hypothalamus via an elongated stalk (Figure 22.2). It is anatomically divided into an adenohypophysis, and an adenohypophysis. Adenohypophysis comprises two components that are pars distalis and intermedia. The pars distalis region in pituitary is commonly referred to as anterior pituitary, is responsible for the production of growing hormone (GH) as well as prolactin (PRL) and thyroid stimulating hormone (TSH) as well as adrenocorticotrophic hormonal hormone (ACTH) as well as LH, luteinizing hormone (LH) and Follicle stimulant hormone (FSH). Pars intermedia only secretes one hormone, melanocyte-stimulating hormone (MSH). In humans the pars intermedia is almost joined with the pars distalis. The neurohypophysis (pars nervosa) is also known as posterior pituitary it stores and releases two hormones known as oxytocin and vasopressin. 

They are produced by the hypothalamus and are transported axonally to the neurohypophysis. In excess, the release of GH triggers an abnormal growth pattern in the body, leading to extreme awe and excitement. In addition, the insufficient production of GH results in a slowed growth, resulting to pituitary dwarfism. Prolactin regulates the development of the mammary glands, and the production of milk within the glands. TSH stimulates the synthesis and release of thyroid hormones by the thyroid gland. ACTH enhances the synthesis of and release of steroid hormones known as glucocorticoids in the adrenal cortex. LH and FSH stimulate gonadol activity and are therefore referred to as gonadotrophins. For males, LH increases the synthesis and release of hormones known as androgens in the testis. In males FSH and androgens control the process of spermatogenesis. Best JEE coaching in Guwahati.

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For females, LH triggers ovulation of full-grown follicles (graafian follicules) and also maintains the corpus of luteum, which is created from the remains of graafian follicles that ovulated after the. FSH is a stimulator of the growth as well as development of female ovarian follicles. MSH is a melanocyte-specific hormone (melanin cells) and regulates the pigmentation on the face. Oxytocin affects the smooth muscles in our body, and increases their contraction. In females, it triggers the uterus to contract vigorously during the time of child birth, and the release of milk out of the gland of mammary. Vasopressin is primarily a stimulant for the kidney, and it stimulates the posterior pituitary anterior pituitary hypothalamus Hypothalamic neuronal circulation 22.2 Illustration of the the pituitary gland and its connection to hypothalamus 2015-16(19/01/2015) Chemical coordination and Interaction 333 resorption and electrolytes through the distal tubules. Best JEE coaching in Guwahati.

This reduces the loss of water through the urine (diuresis). This is why it is known as an anti-diuretic hormone (ADH). 22.2.3 2. The Pineal Gland The pineal gland is located on the dorsal part of the forebrain. Pineal releases a hormone called Melatonin. Melatonin plays an important part to regulate a 24 hour (diurnal) rhythm in our body. It is for instance, it assists to maintain the normal rhythms of the sleep-wake cycle and body temperature. Additionally, melatonin also influences metabolism and pigmentation, as well as the menstrual cycle aswell as our ability to defend ourselves. 22.2.4 Thyroid Gland The thyroid gland is made up of two lobes, which are situated on the opposite one side of the throat (Figure 22.3). The lobes of both are connected with a thin layer of connective tissue known as isthmus. It is comprised of follicles as well as stromal tissues. 

Each thyroid follicle is made up of follicular cells that form an internal cavity. The follicular cells synthesize two hormones: tetraiodothyronine, also the hormone thyroxine (T4 ) along with triiodothyronine (T3 ). Iodine is vital to maintain the normal speed of hormone production in the thyroid. A lack of iodine in our diet can cause hypothyroidism and an increase in the size in the size of the thyroid, which is commonly known as goitre. Hypothyroidism during pregnancy leads to deficient development and maturation of a baby, resulting in reduced growth (cretinism) and mental retardation, a low quotient, skin abnormalities and hair, as well as deaf-mutism. In women of adulthood who suffer from hypothyroidism, it can cause their menstrual cycles to become irregular. Because of thyroid cancer or due to the growth of thyroid nodules glands the rate of synthesis and production of thyroid hormones is increased to abnormal levels that can cause hyperthyroidism that adversely affects body’s physiological. Best JEE coaching in Guwahati.

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 Diagrammatic representation of the positions of Parathyroid and Thyroid (a) The Ventral Side (b) Dorsal sides 2015-16(19/01/2015) 334 BIOLOGY The thyroid hormones play a significant role in the control of metabolic rate of the basal. These hormones also assist in the process of red blood cell development. Thyroid hormones regulate the metabolism of proteins, carbohydrates and fats. Maintaining electrolyte and water balance is also affected through thyroid hormones. Thyroid gland also produces the hormone Thyrocalcitonin (TCT) that regulates level of calcium in the blood. 22.2.5 Parathyroid Gland in humans, there are four parathyroid glands that are located on the back of the thyroid gland. They are two pairs each within the two lobes of thyroid gland (Figure 22.3b). Parathyroid glands produce an peptide hormone known as the parathyroid hormone (PTH). Best JEE coaching in Guwahati.

The release of PTH is controlled by levels of calcium ions in the blood. The hormone called parathyroid (PTH) boosts the Ca2+ concentrations in blood. PTH is a bone-building hormone and enhances an process called bone resorption (dissolutionor demineralisation). PTH also increases the reabsorption of Ca2+ through the renal tubules, and also increases Ca2+ absorption through the consumed food. Therefore, it is obvious it is PTH is a hormone that increases the level of hypercalcemic, i.e., it enhances level of Ca2+ concentrations. Together with TCT it also has a major role to play in the balance of calcium throughout the body. 22.2.6 Thymus The Thymus gland is a organ located between the sternum and lungs on the ventral end of the aorta. The thymus plays a significant role in the growth and function of our immune system. It produces the peptide hormones known as the thymosins. 

Thymosins play an important role in the development of T-lymphocytes that are responsible for cells-mediated immunity. Additionally, thymosins increase the production of antibodies that give you immunity to humor. Thymus cells are degenerated in older people, resulting in decreased production of Thymosins. This means that the immune system of elderly people weaken. 22.2.7 Adrenal Gland Our body is composed of only one adrenal gland one located at the anterior portion within the kidney for each (Figure 22.4 2.2.4.). The gland is made up of two types of tissue. The tissue that is located centrally is known as the adrenal medulla. On the other hand, beyond it is the cortex of adrenal glands (Figure 22.4 B). 2015-16(19/01/2015) Chemical Coordination and Integration 335 The adrenal medulla releases two hormones called adrenaline, also known as epinephrine, and noradrena or norepinephrine. Best JEE coaching in Guwahati.

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These are generally referred to catecholamines. Adrenaline and noradrenaline can be rapidly produced when stressed of all types and during emergencies. They are also known as emergency hormones, also known as the hormones that fight or Flight. The hormones boost alertness, pupil dilation and piloerection (raising of hairs) sweating and other. The hormones also boost the heartbeat as well as the intensity of heart contraction as well as the rate of breathing. Catecholamines can also trigger glycogen’s breakdown, and result in an increase in the amount that glucose is present in the blood. Additionally, they induce the breaking down of proteins and lipids. The adrenal cortex is separated into 3 layers known as zona retinalis (inner layer) and the zona fasciculata (middle layer) and the zona of glomerulosa (outer layer). The adrenal cortex releases a number of hormones, which are commonly referred to corticoids. The corticoids, that are involved in the metabolism of carbohydrate are known as glucocorticoids.Best JEE coaching in Guwahati.

 In the human body, cortisol is the most important glucocorticoid. Corticoids, which control the balance of electrolytes and water in our bodies are known as mineralocorticoids. Aldosterone is the most important mineralocorticoid that we have in our bodies. Glucocorticoids trigger gluconeogenesis, proteolysis and lipolysis; they also hinder the cellular uptake and utilization of amino acids. Cortisol can also be involved in maintaining cardiovascular function as in kidney’s functions. Glucocorticoids specifically cortisol create anti-inflammatory reactions and reduces the immune system. Cortisol is shown in figure 22.4 Diagrammatic representation of: (a) The adrenal gland located above the kidney (b) Section depicting two different parts of the adrenal gland 2015-16(19/01/2015) 336 BIOLOGY increases it to increase RBC production. Aldosterone works primarily in the renal tubules, and it increases the absorption of Na+ and water, as well as the elimination of K+ and the phosphate Ions. Best JEE coaching in Guwahati.

Aldosterone is a key ingredient in maintaining electrolytes as well as body fluid volume, blood pressure, and osmotic pressure. A small amount of androgenic steroids also are released through the adrenal cortex, which contribute to the growth of pubic hair and facial hair throughout puberty. 22.2.8 Pancreas The pancreas is a gland that is composite (Figure 22.1) that acts as an exocrine and an the endocrine gland. The pancreas that is endocrine consists of “Islets that are Langerhans’. There are between 1 and 2 . million Islets that are part of Langerhans in the normal human pancreas that make up just one to two percent in the tissue of pancreas. The two major types of cells that make up the Islet of Langerhans are called B-cells and A-cells. A-cells release an hormone known as glucagon while the b cells secrete insulin. Glucagon is an peptide hormone that plays a crucial role in maintaining normal blood glucose levels. Best JEE coaching in Guwahati.

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It acts mostly on liver cell (hepatocytes) and increases glycogenolysis which leads to an increase in levels of blood glucose (hyperglycemia). Furthermore, this hormone can trigger the process of gluconeogenesis , which is also a factor in hyperglycemia. Glucagon lowers the rate of glucose consumption and utilization. This is why glucagon is a hormone that is hyperglycemic. Insulin is a peptide-hormone that plays a significant function in the control in glucose homeostasis. Insulin acts mostly on the hepatocytes as well as adipocytes (cells of the adipose tissue) and improves cell glucose uptake and utilization. In the end, it is possible to see a rapid transfer of blood glucose into the adipocytes and hepatocytes, resulting in a decrease in level of glucose in the blood (hypoglycemia). Insulin also promotes the conversion of glucose into glycogen (glycogenesis) within the targeted cells. Best JEE coaching in Guwahati.

The blood glucose balance is maintained by insulin and the glucagons. The long-term hyperglycemia can cause an intricate disorder known as diabetes mellitus, which is characterized by the loss of glucose in urine and the formation of harmful compounds called ketones. Diabetic patients are treated by insulin therapy. 22.2.9 Testis The testis pair is located in the scrotal sac (outside abdominal cavity) of males (Figure 22.1). Testis serves two functions as an importantTestis is a sex organ and an gland for endocrine. Testis is made up of seminiferous tubules as well as interstitial or stromal tissue. The Leydig cells , or interstitial cells found in intertubular spaces produce a class of hormones known as androgens. They are primarily testosterone. Androgens regulate development maturation, functions and growth of male accessory sex organs, such as the epididymis and vas deferens and seminal vesicles prostate gland, urethra, and more.

 The hormones promote muscle development, growth of facial and axillary hairs and aggressiveness, as well as low volume of voice, and more. Androgens play an important role in stimulating the process of the process of spermatogenesis (formation of the spermatozoa). Androgens influence neurons in the brain, and can influence the sexual behavior of males (libido). They cause anabolic (synthetic) impacts on carbohydrate metabolism and protein. 22.2.10 Ovary Females possess an ovaries pair that is situated within abdominal fat (Figure 22.1). The ovary is the main female organ for sex that produces an the ovum each menstrual cycle. Additionally, the ovary produces two types of hormones steroid like testosterone and progesterone. Ovary is comprised of ovarian follicles, tissue stroma. The estrogen is synthesized and secreted mostly by developing Ovarian follicules. Best JEE coaching in Guwahati.

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Following an ovulation, the follicle that ruptured transforms into an organ called corpus lauum that secretes progesterone in large quantities. Estrogens perform a variety of actions, including stimulating growth, activity of female organs for sex, the development of ovarian follicles growing and the manifestation of women’s secondary sexual characters (e.g. high voice pitch, etc. ) Mammary gland development. Estrogens also regulate sexual behavior of females. Progesterone supports pregnancy. Progesterone is also a stimulant for the mammary glands, and triggers the development of alveoli (sac-like structures that contain milk) and also the production of milk. 22.3 HORMONES OF THE HEART, KIDNEY, AND GASTROINTESTINAL TRACT You now know what the glands of the endocrine system are as well as their hormones. However, as was mentioned earlier, hormones can also be released by certain tissues that do not have glands that produce hormones. Best JEE coaching in Guwahati.

For instance the atrial wall in our heart produces an significant peptide hormone, called atrial natriuretic factors (ANF) which lowers blood pressure. If blood pressure increases, ANF is secreted which results in the dilation of blood vessels. This decreases blood pressure. 2015-16(19/01/2015) 338 BIOLOGY The juxtaglomerular cell of kidney secrete the peptide hormone erythropoietin that stimulates erythropoiesis (formation of RBC). Endocrine cells found in various regions of the stomach and intestines produce 4 major peptide hormones which include gastrin, cholecystokinin, Cholecystokinin (CCK) along with gastric inhibitory propeptide (GIP). Gastrin affects the gastric glands, and it stimulates the release of pepsinogen and hydrochloric acid. Secretin is a hormone that acts on the pancreas’ exocrine gland and triggers the release of bicarbonate and water Ions. CCK affects both the gall bladder and pancreas. It also stimulates the release of pancreatic enzymes as well as the bile juice. GIP reduces gastric secretion as well as motility. 

Other non-endocrine tissues also secrete growth factors, which are hormones. These factors are essential for the normal growth of tissues and their repairing/regeneration. 22.4 MECHANISMS of HORMONE The hormones exert their effects on the target tissues by binding to certain hormone receptors, which are proteins that reside within the targeted tissues only. The hormone receptors found on the cell membranes of target cells are referred to as membrane-bound receptors, and those receptors within the cell of the target are known as intracellular receptors. They are typically nuclear receptors (present in the nucleus). The binding of a hormone its receptor causes an emergence of a receptor-hormone complex. Each receptor is specific to a single hormone and therefore receptors are unique to. Best JEE coaching in Guwahati.

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The formation of a hormone receptor complex triggers certain biochemical modifications in the targeted tissue. The target tissue’s metabolism and physiological functions are controlled by hormones. Based on their chemical structure hormones can be classified into categories : (i) peptide, polypeptide and protein hormones (e.g. insulin and pituitary hormones, glucagon hypothalamic hormones, for example.) (ii) hormones (e.g. cortisol testosterone, estradiol, and progesterone) (iii) Iodothyronines (thyroid hormones) (iv) amino-acid derivatives (e.g. Epinephrine, for instance). Hormones that interact with membrane receptors usually do not get into the cell of the target but instead produce secondary messengers (e.g. (cyclic IP3, AMP Ca++, etc.)) which then regulate metabolism in cells (Figure 22.5a). Hormones that connect through intracellular receptors (e.g. steroids, hormones, iodothyronines, etc.) typically control the expression of genes or chromosome functions through the interplay of hormone-receptor complexes with genes. Best JEE coaching in Guwahati.

Biochemical reactions that accumulate cause the development and physiological impacts (Figure 22.5b). 2015-16(19/01/2015) Chemical coordination and Interaction 339 Figure 22.5 Diagrammatic depiction of the mechanism for hormone action: (a) Prohormone (b) Steroid hormone (a) (b) 2015-16(19/01/2015) (b) 2015-16 (19/01/2015) BIOLOGY A SUMMARY There are certain substances that function as hormones and offer chemicals that coordinate, and regulation within your body. They regulate the growth, metabolism and growth in our bodies, including the glands of the endocrine or some cells. The endocrine system consists of hypothalamus, pituitary , adrenal glands, thyroid, pineal pancreas, parathyroid the gonads, and the thymus (testis and the ovary). Additionally several other organs like the e.g. stomach tract kidneys heart, and heart, etc. are also responsible for hormones.

 The pituitary gland can be divided into three parts, referred to as pars distalis intermedia, and pars nervosa. Pars distalis releases six hormones called trophic. Pars intermedia only secretes one hormone, whereas Pars nervosa (neurohypophysis) produces two hormones. The pituitary hormones control the growth and development of the somatic tissues and the activity of the endocrine glands in the peripheral. The pineal gland produces melatonin which plays a crucial part to regulate the 24-hour (diurnal) rhythms in our bodies (e.g. and the cycles of sleep and the levels of alertness and body temperature.). Thyroid gland hormones have a significant part in the control of metabolism of basal, the growth and growth of central nerve system, erythropoiesis and metabolism of proteins, carbohydrates and fats, menstrual cycles. Another thyroid hormone i.e. the thyrocalcitonin hormone, regulates the levels of calcium in the blood by reducing it. Parathyroid glands produce the hormone called parathyroid (PTH) which raises levels of blood Ca2+ levels. Best JEE coaching in Guwahati.

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It also plays a significant part in maintaining calcium homeostasis. Thymus glands secrete Thymosins that play an important part in the differentiation of T-lymphocytes that offer cell-mediated immunity. Additionally, thymosins boost the production of antibodies for the purpose of providing humoral immunity. The adrenal gland consists from the adrenal medulla, which is located centrally. gland and the outer cortex of the adrenal gland. The adrenal medulla releases norepinephrine as well as epinephrine. These hormones improve alertness, pupil dilation, piloerection and heartbeat, the strength of contractions in the heart, the rate of breathing, glycogenolysis, proteolysis, lipolysis. The adrenal cortex releases mineralocorticoids as well as glucocorticoids. Glucocorticoids trigger gluconeogenesis and lipolysis, proteolysis and the cardio-vascular system, erythropoiesis blood pressure and glomerular filtration rate. Best JEE coaching in Guwahati.

They also reduce inflammation by reducing the immune response. Mineralocorticoids regulate electrolyte and water content of the body. The pancreas in the endocrine pancreas releases gluca and insulin. Glucagon stimulates glycogenolysis as well as gluconeogenesis which results in hyperglycemia. Insulin boosts glucose uptake and use as well as glycogenesis, which results in hypoglycemia. The deficiency of insulin and/or the resistance to insulin results in a condition called diabetes mellitus. The testis produces androgens that stimulate the growth maturation, functions and growth of the male accessory sexual organs, the appearance of male secondary sexual sex characters and spermatogenesis. It also influences male sexual behavior anabolic pathways and the process of erythropoiesis. The ovary releases hormones like estrogen as well as progesterone.

 Estrogen increases 2015-16(19/01/2015) chemical coordination and integration 341 development and growth of female accessory organs and secondary sexual characters. Progesterone is a key factor in maintaining the pregnancy, as well as the development of the mammary gland as well as lactation. Atrial walls of the heart creates atrial natriuretic factors that lower the pressure of blood. Kidney produces erythropoietin that stimulates the process of erythropoiesis. The gastrointestinal tract produces gastrin, secretin and the gastric inhibitory protein and cholecystokinin. They regulate the release of digestive juices and assist in digestion. Metabolism along with Jet engines are the end of the path) to flow thermodynamically downwards. In turn, the pathway is able to generate ATP in a variety of concentrations of product and substrate.Best JEE coaching in Guwahati.

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It is the expression “turbo design” that is derived from the turbo engines found in jet aircraft, is a description of this process. An excellent example is glycolysis. It is the process that captures energy and converts the glucose hexose into the Pyruvate (Figure 8.1). Jet engines generate propulsion by mixing air and fuel to produce rapid-moving, hot and expanding exhaust gases that blast out of the back. A portion of the air that is brought in from its front is channeled into compressors, where the pressure is increased before being pumped into combustion chambers where it is mixed the fuel molecules. When the fuel molecules that are burning expand, they move through turbines equipped with fan blades which drive the compressors. Best JEE coaching in Guwahati.

A key aspect in this procedure is the fact that exhaust gasses from hot combustion are being recirculated back into the engine in order to accelerate the fuel input phase. This chapter describes the way in which carbohydrate fuel is used by living cells, with the same incredible effectiveness. Systems biology can help aid in understanding glycolysis and other biochemical pathways? The modern species result of millions of years of hard-working natural selection that has allowed organisms to adapt to their diverse environments. The process of selection also regulates the metabolic pathways responsible for the biochemical changes that sustain the life of the organism. When biologists studying systems biology examined the metabolic processes and discovered that evolution, which operates within the constraints of thermodynamic and kinetic is converged time and again to form a tiny set of patterns. 

Catabolic pathways that breakdown organic compounds and generate energy offer an illustration. They generally possess two features: maximum ATP production as well as the efficiency of kinetics (i.e. little or no delay in responding to fluctuations in cell metabolic demands). Living organisms have catabolic pathways that are optimized which are primarily facilitated by extremely exergonic reactions that occur in the beginning of an avenue. The initial “activation” of the nutrient molecules causes the subsequent reaction that generate ATP (usually close to GlucoseMetabolism as well as Jet Engines at at the at the end of the process) to be run thermodynamically downhill. This means that the pathway is able to generate ATP with varying concentrations of substrate and products. It is the expression “turbo design” in reference to the turbo engines of jet aircraft, is a description of this process. Best JEE coaching in Guwahati.

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An excellent illustration is glycolysis, which is the process that captures energy and converts the glucose hexose into Pyruvate (Figure 8.1). Jet engines generate propulsion by mixing air and fuel to produce rapidly-moving, hot, and expanding exhaust gases that explode out of the back. A portion of the air that is that is drawn into in front of an engine gets channeled into compressors, where the pressure rises before entering combustion chambers, where it mixes in with the molecules of fuel. The burning fuel molecules expand, they pass through turbines with fan blades, which operate the compressors. One of the most important aspects to this method is that the hot exhaust gases are being recirculated back into the engine in order to speed up the fuel input process. Best JEE coaching in Guwahati.

This chapter will explain how carbohydrate fuels are burned by living cells, with the same incredible effectiveness. Systems biology can help aid in understanding glycolysis and other biochemical pathways? The modern species result of many billions of years of arduous natural selection that has helped adapt organisms to their diverse environments. This process also controls the metabolic pathways that control the biochemical processes that support the life of an organism. As biologists from systems biology studied the processes of metabolism and discovered that evolution, which operates within the constraints of thermodynamic and kinetic has been able to converge again and again to form a tiny set of patterns. Catabolic pathways that breakdown organic compounds and generate energy offer an excellent illustration. They typically feature two key characteristics: high ATP production as well as the efficiency of kinetics (i.e. little or no reaction time for changes to the cellular metabolic demands). 

Living organisms have developed catabolic pathways that have been optimized by utilizing extremely exergonic reactions that occur that begin an underlying pathway. The initial “activation” of nutrients is what triggers subsequent reactions that produce ATP (usually close to GlucoseThe Chemical Reactions in the Glycolytic pathway Glycolysis is illustrated as Figures 8.3. The 10 reactions in glycolytic pathways are as the following. 1. A process for the synthesis and synthesis of glucose-6-phosphate. After entering a cell the glucose and others sugar molecules get processed and phosphorylated. The phosphorylation blockades the transport of glucose from cells and enhances the reactivity and reactivity of oxygen present in the isomer of phosphate. Numerous enzymes, referred to as Hexokinases, facilitate the phosphorylation process of hexoses inside every cell in the body. Best JEE coaching in Guwahati.

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ATP is a cosubstrate that occurs in the process, gets linked with Mg2. (ATP-Mg2 complexes are typical in kinase-catalyzed reaction.) In intracellular conditions, the reaction cannot be reversed; this means that the enzyme is not able to store or accept the product of the reaction within its active location, regardless of the amount of G-6-P.2. Conversion of glucose-6-phosphate to fructose-6-phosphate. During reaction 2 of glycolysis, the open chain form of the aldose glucose-6-phosphate is converted to the open chain form of the ketose fructose-6-phosphate by phosphoglucose isomerase (PGI) in a readily reversible reaction: Phosphoglucose isomerase Glucose-6-phosphate Fructose-6-phosphateRecall that the isomerization reaction of glucose and fructose involves an enediol intermediate (Figure 7.16). This transforms C-1 in the fructose derivative accessible to phosphorylation. The hemiacetal hydroxy group in glucose-6-phosphate is more difficult phosphorylate. 3. Best JEE coaching in Guwahati.

The phosphorylation of fructose-6-phosphate. Phosphofructokinase-1 (PFK-1) irreversibly catalyzes the phosphorylation of fructose-6-phosphate to form fructose-1,6-bisphosphate: +8.1 Glycolysis 7 The PFK-1-catalyzed reaction is irreversible under cellular conditions. This is the first step that is committed in glycolysis. Unlike glucose-6- phosphate and fructose-6-phosphate, the substrate and product, respectively, of the previous reaction, fructose-1,6-bisphosphate cannot be diverted into other pathways. Injecting a second molecule ATP serves a variety of purposes. For one, since ATP is utilized as a chemical phosphorylator and the reaction is able to proceed with a significant reduction in the free energy. After fructose-1,6-bisphosphate has been synthesized, the cell is committed to glycolysis. Because fructose-1,6-bisphosphate eventually splits into two trioses, another purpose for phosphorylation is to prevent any later product from diffusing out of the cell because charged molecules cannot easily cross membranes. 

 Cleavage of fructose-1,6-bisphosphate. Stage 1 of glycolysis ends with the cleavage of fructose-1,6-bisphosphate into two three-carbon molecules: glyceraldehyde-3-phosphate (G-3-P) and dihydroxyacetone phosphate (DHAP). This is an aldol-cleavage, which is the reason for it’s name, aldolase. Aldol cleavages are the opposite of aldol condensations. This is which are described on page. xxx. In aldol cleavages an aldehyde and a ketone are products.Glyceraldehyde-3-phosphate Although the cleavage of fructose-1,6-bisphosphate is thermodynamically unfavorable (G  23.8 kJ/mol), the reaction proceeds because the products are rapidly removed. 5. The interconversion of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Of the two products produced by the aldolase reaction only G-3-P serves as a substrate the subsequent reaction in glycolysis. To avoid the elimination of the other three-carbon unit in that glycolytic route, triosephosphate isomerase is responsible for the reversible conversion from DHAP to G-3-P. Best JEE coaching in Guwahati.

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After this reaction, the first glucose molecule has been transformed into two G-3-P molecules. 6. Oxidation of glyceraldehyde-3-phosphate. During reaction 6 of glycolysis, G-3-P undergoes oxidation and phosphorylation8 CHAPTER EIGHT Carbohydrate Metabolism glycerate-1,3-bisphosphate, contains a high-energy phosphoanhydride bond, which may be used in the next reaction to generate ATP: This complex process is catalyzed by glyceraldehyde-3-phosphate dehydrogenase, a tetramer composed of four identical subunits. Each subunit is home to a binding site for G-3P and another site for NAD, which is an Oxidizing agent. In the process of forming an acovalent thioester-bond to the substrate (Figure 8.4) the hydroide is formed. (H:) gets transferred into NAD within the active region. NADH is the reduced version of NAD is then removed from the active site, and is replaced by an inbound NADH. Best JEE coaching in Guwahati.

Adducts of the acyl enzyme gets attacked by phosphate inorganic, and the product then leaves it’s active area. 7. Transfer of phosphoryl groups. In this reaction ATP is synthesized as phosphoglycerate kinase catalyzes the transfer of the high-energy phosphoryl group of glycerate-1,3-bisphosphate to ADP: Reaction 7 is an example of a substrate-level phosphorylation. Because the synthesis process for ATP is very endergonic, it needs the energy source. In substratelevel phosphorylations, ATP is produced by the transfer of a phosphoryl group from a substrate with a high phosphoryl transfer potential (glycerate-1,3-bisphosphate) (refer to Table 4.1) to produce a compound with a lower transfer potential (ATP) and therefore G  0. Because two molecules of glycerate-1,3-bisphosphate are formed for every glucose molecule, this reaction produces two ATP molecules, and the investment of phosphate bond energy is recovered. 

ATP synthesizing later in the pathway is an increase in net value. 8. The conversion of 3-phosphoglycerate into 2-phosphoglycerate. Glycerate-3-phosphate has a low phosphoryl group transfer potential. This makes it not a good option for ATP synthesizing (G for ATP synthesizing is -30.5 KJ/mol). Cells convert glycerate-3-phosphate with its energy-poor phosphate ester to phosphoenolpyruvate (PEP), which has an exceptionally high phosphoryl group transfer potential. (The normal free energies of hydrolysis of glycerate-3 phosphate as well as PEP is 12.6 and 61.9 kJ/molrespectively.) In the initial step of this process (reaction 8) The phosphoglycerate-mutase enzyme catalyzes transformation of C-3 phosphorylated substance into a C-2 phosphorylated one by a two-step addition/elimination process. Best JEE coaching in Guwahati.

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H+ Pi Glyceraldehyde-3-phosphate Glycerate-1,3-bisphosphateGlyceraldehyde-3-Phosphate Dehydrogenase Reaction In the first step the substrate, glyceraldehyde-3-phosphate, enters the active site. The enzyme catalyzes the reactions of the substrate by an sulfhydryl group inside the site of active (step 2) the substrate gets converted into a form of oxygen (step 3.). It is then bound noncovalently NADH is converted into the cell-surface NAD (step 4.). The displacement of the enzyme with an inorganic phosphate (step 5) releases the product, glycerate-1-bisphosphate and the enzyme is returned back to its original state. 0 10 Chapter Eight Carbohydrate Metabolism 9. The dehydration process of 2-phosphoglycerate. Enolase catalyzes the dehydration of glycerate-2-phosphate to form PEP: PEP has a higher phosphoryl group transfer potential than does glycerate2- phosphate because it contains an enol-phosphate group instead of a simple phosphate ester. Best JEE coaching in Guwahati.

The reason behind this distinction is revealed in the following reaction. There are two distinct isomeric forms. The enol type has carbon-carbon double bonds and the one-hydroxyl group. Enols are as equilibrium forms with keto form, which is carbonyl-rich. The process of converting keto into the enol types, also known as automers, is known as tautomerization. It is limited due to the presence of the group phosphate, and its resonance stability of phosphate ion that is free. In the end, the transfer of phosphoryl to ADP during reaction 10 has been extremely preferred. 10. Synthesis of Pyruvate. In the final step of glycolysis, pyruvate Kinase is responsible for the exchange of a phosphoryl molecule from PEP into ADP. 2 compounds of ATP are produced for each one molecule that is made up of glucose.The Fates of Pyruvate When oxygen is present (left) aerobic organisms completely oxidize the pyruvate to H2O and CO2. 

If oxygen is not available, pyruvate is converted into a variety that are reduced molecules. In certain cells (e.g. yeast) CO2 and ethanol are created (middle). In other cells (e.g. muscles cells) homolactic fermentation is a process where lactate is the sole organic substance (right). Some microorganisms employ the heterolactic process of fermentation (not illustrated) that generate other alcohols or acids along with lactate. In all processes of fermentation the main goal is to replenish NAD+ to allow glycolysis to continue. PEP is irreversibly transformed into Pyruvate due to the fact that in this reaction –the movement of the phosphoryl molecule from an molecule that has an extremely high transfer potential to a molecule with less transfer potential, there is a huge cost of energy lost (refer at Table 4.1). This energy loss is caused with the spontaneous transformation (tautomerization) that occurs in the inol form of pyruvate, to its more durable keto version. Best JEE coaching in Guwahati.

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The 10 glycolysis reactions are shown on Figure 8.5. What are the Fates of Pyruvate In terms of energy, the outcome from glycolysis results in the generation from two ATPs, and two NADHs for each glucose molecule. Pyruvate is the other product of glycolysis, remains an energy-rich moleculethat produces a significant volume of ATP. The extent to which additional energy is produced it is dependent on the type of cell and the supply of oxygen. Under aerobic conditions, the majority cells within the body convert pyruvate to acetyl CoA, the primary base for the citric acid chain, an amphibolic process which completely oxidizes the two carbons in acetyl to create CO2 as well as the reduced molecules FADH2 and NADH. (An amphibolic pathway plays a role both in catabolic and anabolic processes.) It is which is a sequence of oxidation-reduction reactions transfer electrons in NADH and FADH2 to the O2 form water. Best JEE coaching in Guwahati.

The energy released by electron transport is paired with an enzyme that produces ATP. In anaerobic conditions, the oxidation process of pyruvate continues to be hindered. A number of cells and organisms compensate by converting this molecule to a more reduced organic compound and regenerating the NAD required for glycolysis to continue (Figure 8.6)Recycling of NADH During Anaerobic Glycolysis The NADH produced during the conversion of glyceraldehyde-3-phosphate to glycerate1,3-bisphosphate is oxidized when pyruvate is converted to lactate. This allows cells to continue to produce ATP in anaerobic environments for so long as glucose is present. In muscle cells that contract rapidly the need for energy is very high. When the O2 supply is exhausted the lactic acid fermentation process provides enough NAD for glycolysis (with its low levels in ATP production) to last for a brief period. 

 In yeast as well as certain bacteria, pyruvate is decarboxylated and forms acetaldehyde that is then diminished by NADH to create alcohol. (In decarboxylation reactions an organic acid loses an oxygen-carboxyl group in CO2.) that the hydride ion acceptor molecule NAD+ is a cosubstrate in the reactoin catalyzed by glyceraldehyde-3-phosphate dehydrogenase.) It is believed that this process for NAD regeneration is known as fermentation. Muscle cells as well as red blood cells and a few bacteria (e.g., Lactobacillus) create NAD by transforming the lactate into pyruvate: decarboxylase CO2 from pyruvate. AcetaldehydeMost compounds of alcohol get eliminated in the liver through two processes. The first is that alcohol is oxidized and forms the acetaldehyde. The reaction, which is catalyzed through alcohol dehydrogenase produces huge quantities of NADH After the production of acetaldehyde, it is converted into acetate via aldehyde-dehydrogenase. It catalyzes a reaction which also creates NADH. Best JEE coaching in Guwahati.

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The most common consequence of alcohol-related intoxication is the increase in lactate levels in blood. What is the reason for this occurs? dehydrogenase Aldehyde4 CHAPTER 8 Carbohydrate Metabolism Go to the website of the study companion at www.oup.com/us/mckee to go through the Biochemistry in the context of fermentation. The key concepts are that during glycolysis, glucose is transformed to two pyruvate molecules. A tiny portion of the energy stored in two molecules comprised of ATP in addition to NADH. * In anaerobic species, the pyruvate metabolites are converted into waste products during an process known as fermentation. * When there is oxygen, aerobic species convert pyruvate to H2O and CO2. This process, known as alcohol fermentation, is employed commercially to make beer, wine and bread. Best JEE coaching in Guwahati.

Certain bacteria produce organic molecules that are not alcohol. For instance, Clostridium acetobutylicum, an organism that is related to botulism’s causative agents and tetanus, makes butanol. It was until recently that this organism was utilized commercially to produce butanol, an alcohol that is used to make synthetic fibers and detergents. The petroleum-based synthetic process has replaced the fermentation process by microbial. The energy of Glycolysis In glycolysis it releases energy by the breakdown of glucose to pyruvate can be linked to the phosphorylation process of ADP which results in a net yield to 2 ATP. But, the evaluation of typical free energy fluctuations of the various reaction (Figure 8.8) doesn’t provide a clear explanation for the effectiveness of this process. An alternative method for studying changes in free energy is to consider the conditions (e.g. pH, pH, and concentrations of metabolites) that cells function. As shown in Figure 8.8 the free energy changes observed by red blood cell metabolites show there are only 3 reactions are markedly negatively G values.

 Free Energy Changes during glycolysis in red blood cells The standard Free Energy Changes (GG) for the reactions involved in glycolysis are not consistent (upper graph). In contrast, actual free energy values (G) based on metabolite concentrations measured in red blood cells (lower plot) clearly illustrate why reactions 1, 3, and 10 (the conversions of glucose to glucose-6-phosphate, fructose-6-phosphate to fructose-1,6-bisphosphate, and phosphoenolpyruvate to pyruvate, respectively) are irreversible. The reversibility that is readily available for the remaining reactions can be seen by their close to zero G values. (GLU = glucose, G6P = glucose-6-phosphate, F6P = fructose-6-phosphate, FBP = fructose-1,6-bisphosphate, GAP = glyceraldehyde phosphate, PG3 = glycerate-3-phosphate, PG2 = glycerate-2-phosphate, PEP = phosphoenolpyruvate, PYR = pyruvate, LAC = lactate) Note that the conversion of DHAP to GAP is not counted in this list, since FBP is broken into GAP and DHAP, which is reconverted into GAP. Best JEE coaching in Guwahati.

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Saccharomyces cerevisiae, and Crabtree Effect Crabtree Effect What special characteristics of Saccharomyces cerevisiae make it beneficial in the making of beer, wine, and bread? Saccharomyces cerevisiae, a eukaryotic microorganismthat has had a significant impact on human. Beginning in the Neolithic age and continuing to the present day, this organism is used to convert carbohydrate-containing food into the wine, beer, and bread that many humans consider indispensible to life. What characteristics are the unique characteristics of S. cerevisiae makes it unique in the most ancient of biotechnology? While many yeast species convert carbohydrates into ethanol and CO2 however, it is only S. cerevisiae is able to produce the molecules in large quantities. An easy experiment can help to explain the reason. If fruits that are fleshy like grapes are crushed and put in a vessel that is heated, they begin to ferment. Best JEE coaching in Guwahati.

When the fermentation process begins it is possible to look over the microorganisms in the vat reveals a variety of varieties of microorganisms however, there are only a only a few S. cerevisiae. The process of fermentation continues (and the ethanol content grows) However, S. cerevisiae cells are a greater percentage of the microbes, until they are the only microbes in the environment. What happens when S. cerevisiae accomplishes this feat has been the focus of a lot of research. Not just because of the importance of the traditional biotechnology for fermentation. The idea of creating biofuels derived made from the cellulose (not from a staple food item like corn) in a cost-effective, affordable manner remains unsolved. The primary biological reason for S. cerevisiae to make carbohydrates in a controlled manner and to dominate its environment can be explained through the Crabtree effect, which will be discussed later. 

What is the Crabtree effect S. cerevisiae is a facultative anaerobe, which means it is able to generate energy in the presence or absence of O2 through an aerobic process (the citric acid cycle the electron transport mechanism and the oxidative the phosphorylation) and fermentation as well as fermentation. In contrast to most organisms that ferment, S. cerevisiae can also produce sugar even in presence of O2. As fructose and glucose levels rise, pyruvate can be taken away of the citric acid process (the first stage of the aerobic energy production) to ethanol synthesis through conversion to CO2 and acetaldehyde through pyruvate decarboxylase. This process, where glucose inhibits aerobic metabolism is known as the Crabtree effect. (In the majority of organisms that utilize oxygen, the Pasteur effect is evident glycolysis decreases when oxygen is present.Best JEE coaching in Guwahati.

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 In S. cerevisiae cells high glucose levels result in changes in gene expression. These changes lead to the introduction of hexose transporters in the plasma membrane (resulting in the rapid flow of glucose into cells) as well as the synthesis of glycolytic enzymes and the inhibition of glycolysis. FIGURE 8.10 Carbohydrate metabolism: gluconeogenesis and glycolysis In gluconeogenesis, which happens in the event that blood sugar is low, and glycogen in the liver is depleted. Seven from the 10 steps in glycolysis go through a reverse. Three irreversible glycolytic processes are avoided by alternate reactions. The main ingredients for gluconeogenesis include amino acids (derived from muscles) as well as lactate (formed in red blood cells) as well as the glycerol (produced by the degrading of triacylglycerols). Contrary to the processes of glycolysis, which take place exclusively in the cytoplasm, processes of gluconeogenesis that are catalyzed through pyru carboxylase, and in certain varieties, PEP carboxykinase are found within mitochondria.Best JEE coaching in Guwahati. 

The reaction catalyzed by glucose-6-phosphatase takes place in the endoplasmic reticulum. Be aware that glycolysis and gluconeogenesis cannot occur at the same time. The glycolysis process involves pyruvate, which can be transformed into Acetyl-CoA (not illustrated) as well as to lactate.Gluconeogenesis 21 Turbo Design Could be Risky Why should turbo design processes be strictly monitored? The catabolic pathways that are turbo design, like glycolysis is optimized and efficient. However, the initial stages of these pathways have to be controlled negatively to avoid the accumulation of intermediates and excessive use of fuel. The four ATPs generated from the glucose molecules are transferred back to the fuel input phase of the pathway in order to propel the process forward. Based on the evidence of the fact that it is used by a majority of living organisms today glycolysis has been an extremely efficient energy generation strategy. 

However, it isn’t 100% perfect however. Under certain circumstances, the turbo design of glycolysis makes some cells vulnerable to a phenomenon called “substrate-accelerated death”. Certain varieties of yeast cells that have been modified such as those that cannot grow anaerobically using glucose, even though they have an entire glycolytic pathway. The mutants are killed when exposed to Biochemistry In PERSPECTIVE high levels of glucose. Amazingly, research efforts have revealed that defects in TPS1, the gene that codes for the catalytic subunit of trehalose-6-phosphate synthase, are responsible. Trehalose-6-phosphate (Tre-6-P), an -(1,1)-disaccharide of glucose, is a compatible solute Water, Abiotic Stress, and Compatible Solutes) used by yeast and various other organisms to resist several forms of abiotic stress. Evidently, Tre-6-P acts as an enzymatic inhibitor of HK (and could be an insulin transporter). Best JEE coaching in Guwahati.

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If there is no functioning TPS1 protein, and once glucose is available, glycolytic flux in mutant cells quickly increases. Within a short amount of duration, as a result of the turbo-design in the process, all available phosphate is incorporated into glycolytic intermediates and cells’ ATP level is insufficient to support the process in the cell. This and other similar examples of substrate-accelerated cell death in other species provide insight into the importance of the intricate regulatory mechanisms observed in living organisms. Defects in the intricate regulatory mechanism that controls a turbo design pathway can make an organism vulnerable to substrate-accelerated death through uncontrolled pathway flux. 1. Production of PEP. PEP synthesis from pyruvate calls for two enzymes: the pyruvate carbonoxylase as well as PEP carboxykinase. Pyruvate carboxylase is found in mitochondria, transforms pyruvate Oxaloacetate (OAA) the conversion of CO2 into OAA is a product. Best JEE coaching in Guwahati.

OAA is controlled by biotin, a coenzyme (p. xxx) which is attached to the active site of the enzyme. Pyruvate22 CHAPTER 8 Carbohydrate Metabolism OAA then gets decarboxylated, and phosphorylated by the PEP car boxykinase as an action triggered by the hydrolysis of the guanosine triphosphate (GTP) PEP carboxykinase is located in mitochondria from some species, and also within the cytoplasm of different species. In humans, this enzymatic function is present throughout both organelles. Since the mitochondrial membrane is not permeable to OAA cells lacking mitochondrial PEP carboxykinase are able to transfer OAA in the cytoplasm through malate shuttle. Through this process, OAA transforms to malate via mitochondrial malate deshydrogenase. Following the transfer of malate across the mitochondrial membrane The reverse reaction (to create OAA with NADH) is catalyzed by the cytoplasmic malate dehydrogenase. 

The malate shuttle allows gluconeogenesis to continue because it provides the NADH required for the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase. 2. Conversion of fructose-1,6-bisphosphate to fructose-6-phosphate. The irreversible PFK-1-catalyzed reaction in glycolysis is bypassed by fructose-1,6-bisphosphatase: This exergonic reaction (G  -16.7 kJ/mol) is also irreversible under cellular conditions. ATP cannot be regenerated also inorganic and organic phosphate (Pi ) is also generated. Fructose-1,6-bisphosphatase is an allosteric enzyme. Its activity is stimulated by citrate and inhibited by AMP and fructose2,6-bisphosphate.8.2 Gluconeogenesis 23 Patients with von Gierke’s disease (a glycogen storage disease) lack glucose-6- phosphatase activity. Two of the most prominent signs of this disorder are hypoglycemia as well as the presence of lactic acidosis. Best JEE coaching in Guwahati.

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What is the reason for these symptoms are present. In the process of forming glucose in glucose-6-phosphate. Glucose-6-phosphatase, found only in liver and kidney, catalyzes the irreversible hydrolysis of glucose-6-phosphate to form glucose and Pi . The resulting glucose is released into blood. Each of the above reactions is followed by an irreversible counter-reaction in glycolysis. Each pair of these pair reactions is referred to as a “substrate cycle. Because they are controlled in a coordinated manner (an activater of an enzyme that catalyzes the forward reaction functions to inhibit the enzyme responsible for catalyzing that reverse reaction) Very little energy is lost, regardless of the fact that both enzymes might be operating simultaneously. Control of the flux (regulation that regulates the movement of substrate as well as elimination of the substance) is more efficient if the product’s accumulation is transient and channeled back into the process. Best JEE coaching in Guwahati.

The catalytic speed of forward enzyme will stay high when the amount of substrate is maximised. The increase in catalytic efficiency far more than compensates for the minor energy cost of recycle the products. Gluconeogenesis is a consuming energy process. Instead of producing ATP (as the glycolysis process does) it is an hydrolysis process that involves six high-energy bonding phosphates. Hyperthermia maligna is a rare and genetically-inherited condition that can be caused by surgery and certain anesthetics. A significant (and dangersome) increase within the body (as as high as 112F) is followed by muscle stiffness and acidosis. The muscle spasms are caused by the massive discharge of calcium through the sarcoplasmic-reticulum an organelle that stores calcium inside muscles cells. Acidosis is caused by excessive production of lactic acid. A prompt and effective treatment to reduce body temperature and counteract acidosis is crucial for the survival of the patient. 

One possible cause of this condition is the inefficient cycle between glycolysis and the process of gluconeogenesis. Discuss why this is an acceptable explanation. Answer the question. 8.4 After looking at the gluconeogenic pathway’s reaction summary presented here, take note of each of the components in the equation. It is important to note that the hydrolysis of each nucleotide release the proton.[] QUESTION 8.5 Malignant Hyperthermia von Gierke’s Disease. Carbohydrate metabolism Figure 8.11 Aspects of the Cori Cycle during strenuous exercise Lactate is made anaerobically by muscle cells. After passing through blood to the liver, lactate is converted to glucose by gluconeogenesis.Gluconeogenesis Substrates As previously mentioned, several metabolites are gluconeogenic precursors. Three of the major substrates are briefly described. Best JEE coaching in Guwahati.

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Lactate is released by red blood cells as well as other cells with mitochondria and have lower levels of oxygen. Within the Cori cycle the release of lactate occurs through the muscle during exercises (Figure 8.11). When lactate is transferred into the liver, it is converted to pyruvate through lactate dehydrogenase, and later to glucose via the process of gluconeogenesis. Glycerol is a product of the metabolism of fat in adipose tissue, gets transferred to the liver through the blood, and is then transformed into glycerol-3-phosphate through the glycerol kinase. The oxidation process of glycerol-3-phosphate into DHAP is triggered when the cytoplasm NAD levels are high.FIGURE 8.12 The Alanine from the Glucose-Alanine cycle is created from pyruvate found in muscle. Once it is transferred into the liver alanine gets transformed into pyruvate through an enzyme called alanine transaminase. Best JEE coaching in Guwahati.

Then, pyruvate can be used in the production of new glucose. Since muscle is unable to synthesize the amino nitrogen molecule urea The glucose-alanine cycle can be used to transfer amino nitrogen into the liver.Of all amino acids that are transformed into glycolytic intermediates (molecules known as glucose-producing) Alanine is the most significant. When muscles are exercised, they produce large amounts of pyruvate, a few substances are transformed to alanine through the transamination process involving glutamate. After it has been transferred into the liver alanine gets transformed back to pyruvate, and later to glucose.Like other biochemical pathways, hormones influence the process of gluconeogenesis through altering the levels of allosteric effectsors and most important rate-determining enzymes. 

As mentioned previously, glucagon depresses the synthesis of fructose2,6-bisphosphate, which releases the inhibition of fructose-1,6-bisphosphatase, and inactivates the glycolytic enzyme pyruvate kinase. The hormones also affect gluconeogenesis through altering the synthesis of enzymes. For example, the production of gluconeogenic enzymes can be stimulated by cortisol, which is a hormone that is produced by the adrenal cortex gland, which aids in the body’s response to stressful conditions. Additionally, the action of insulin results in the creation of new glucokinase molecules as well as the PFK-1 (SREBP1c-induced) and the PFK-2 (glycolysis preferred). Insulin also depresses the synthesis (also via SREBP1c) of PEP carboxykinase, fructose1,6-bisphosphatase, and glucose-6-phosphatase. Glucagon action leads to the synthesis of additional molecules of PEP carboxykinase, fructose-1,6- bisphosphatase, and glucose-6-phosphatase (gluconeogenesis favored). Best JEE coaching in Guwahati.

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Glycolyses are regulated by hormones. as well as gluconeogenesis alter phosphorylation status of specific target proteins within the cell of liver, and this then affects the expression of genes. The most important thing to keep in mind is the fact that both insulin and glucagon exert different effects on the carbohydrate metabolism. The direction of metabolite flux (i.e. the degree to which glycolysis or gluconeogenesis are in active) is mostly determined through the proportion of insulin the hormone glucagon. Following a meal of carbohydrate the ratio of insulin to glucagon is high and glycolysis within the liver dominates over the process of gluconeogenesis. Following a time of fasting or after the consumption of a low-fat and high-fat meal, the ratio of insulin to glucagon is low, and gluconeogenesis within the liver dominates over glycolysis. There is a high level in ATP will be the next major regulator of the reciprocal regulation of gluconeogenesis as well as glycolysis. Best JEE coaching in Guwahati.

It is observed the sense that high levels of AMP the hydrolysis product with low energy, derived from ATP boost the flow through glycolysis, but at cost to gluconeogenesis and lower levels of AMP boost the flow through gluconeogenesis, but at the cost of glycolysis. Although control at the PFK-1/fructose1,6-bisphosphatase cycle would appear to be sufficient for this pathway, control at the pyruvate kinase step is key because it permits the maximal retention of PEP, a molecule with a very high phosphate transfer potential. 8.3 The pentose phosphate pathway The pentose-phosphate pathway is an alternative pathway to glucose oxidation where no ATP is produced. The main products of this pathway include NADPH an reducer that is required in a variety of anabolic processes, as well as ribose-5-phosphate as a structural element of nucleotides and nucleic acid. 

 The pentose-phosphate pathway takes place within the cytoplasm in two phases: oxidative as well as nonoxidative. In the oxidative part of the pathway the conversion of glucose-6-phosphate to ribulose-5 phosphate is supported by the formation from two molecules NADPH. The nonoxidative stage involves the isomerization and condensation several sugar molecules. Three intermediates in this process that are useful in other pathways are ribose-5-phosphate, fructose-6-phosphate, and gly ceraldehyde-3-phosphate. The oxidative stage of the pentose-phosphate pathway is comprised of three different reactions. In the first reaction the glucose-6-phosphate dehydrogenase (G-6-PD) is responsible for the oxidation process of glucose-6-phosphate. 6-Phosphogluconolactone and NADPH are products in this reaction. 6-Phospho-D-glucono--lactone is then hydrolyzed to produce 6-phospho-D-gluconate. Best JEE coaching in Guwahati.

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A second molecule of NADPH is produced during the oxidative decarboxylation of 6-phosphogluconate, a reaction that yields ribulose-5-phosphate. A large portion of NADPH needed for reductive processes (i.e. biosynthesis of lipids) is produced by these reactions. This is why this pathway is the most prevalent within cells in which significant amounts of lipids can be produced, (e.g. the adipose tissues as well as mammary glands, the adrenal cortex along with the liver). NADPH is a key concept Gluconeogenesis which is the process of creating new glucose molecules made from noncarbohydrate precursors, is primarily inside the liver. * The sequence of reactions reverses glycolysis, with the exception of three reactions that skip irreversible steps in glycolysis.also an extremely powerful antioxidant. Best JEE coaching in Guwahati.

(Antioxidants can be defined as substances which impede the burning to other molecules. Their functions in living processes are discussed in chapter 10.) Therefore, the oxidative part of the pentose phosphate process is very active in cells susceptible to the oxidative damages, like Red blood cells. The nonoxidative part of the pathway starts with the conversion of ribulose5 phosphate to ribose-5-phosphate via ribulose-5-phosphate or to xylulose-5,phosphate through ribulose-5phosphat epimerase. The remaining processes of this pathway (Figure 8.14b) transketolase as well as transaldolase perform the interconversion of trioses, pentoses and Hexoses. Transketolase is an TPPrequiring enzyme that can transfer two carbon units from ketose to an aldose. (TPP is thiamine pyrophosphate. It is the coenzyme variant of thiamine. It is also known as vitamin 8.14b The pentose phosphate pathway (b) Nonoxidative Phase. When cells require more NADPH than pentose phosphates, the enzymes in the nonoxidative phase convert ribose-5-phosphate into the glycolytic intermediates fructose-6-phosphate and glyceraldehyde-3-phosphate.

30 CHAPTER EIGHT Carbohydrate Metabolism B1.) Transketolase catalyzes two reaction. In the first reaction, the enzyme transfers a two-carbon unit from xylulose-5-phosphate to ribose-5-phosphate, yielding glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate. In the second transketolase-catalyzed reaction, a two-carbon unit from another xylulose-5-phosphate molecule is transferred to erythrose-4-phosphate to form a second molecule of glyceraldehyde-3-phosphate and fructose-6-phosphate. Transaldolase transfer three-carbon units from an aldose to a ketose. In the reaction catalyzed by transaldolase, a three- carbon unit is transferred from sedoheptulose-7-phosphate to glyceraldehyde-3-phosphate. The products formed are fructose-6-phosphate and erythrose-4-phosphate. The result of the nonoxidative phase of the pathway is the synthesis of ribose-5-phosphate and the glycolytic intermediates glyceraldehyde-3- phosphate and fructose-6-phosphate. Best JEE coaching in Guwahati.

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If pentose sugars aren’t needed for biosynthetic processes, the metabolites that are found in the nonoxidative phase of the pathway transform into glycolytic intermediates, which can be further degraded to create energy or transformed into precursor molecules needed for biosynthetic reactions (Figure 8.15). For this Fructose-1,6-bisphosphate Ribulose-5-phosphate Fructose-6-phosphate Glyceraldehyde-3-phosphate Glucose-6-phosphateFIGURE 8.15 Carbohydrate Metabolism: Glycolysis and the Pentose Phosphate Pathway If the cell requires more NADPH than ribose molecules, it can channel the products of the nonoxidative phase of the pentose phosphate pathway into glycolysis. As this overview of the two pathways illustrates, excess ribulose-5-phosphate can be converted into the glycolytic intermediates fructose-6- phosphate and glyceraldehyde-3-phosphate.Best JEE coaching in Guwahati.

8.4 Metabolism of other Significant Sugars 31 reasons why the pentose phosphate pathway sometimes referred to as monophosphate shunt of hexose. The pentose-phosphate pathway plays a role in production of glucose in the dark photosynthesis (Chapter 13.). The pentose phosphate pathway can be controlled to meet the cells’ requirements at-a-time for NADPH and ribose-5 phosphate. The oxidative process is highly active in cells like liver cells or red blood cells in which the need for NADPH is very high. However, the oxygenative phase is absent on cells (e.g. muscle cells) that produce less or no lipids. (Lipid synthesizing is a significant user of NADPH.) G-6-PD plays a major regulator in the pentose phosphate process. Its function is blocked through NADPH as well as stimulated through GSSG which is the oxidized form of glutathione. 

It is a crucial antioxidant of the cells along with glucose-6-phosphate. Additionally, diets rich in carbohydrates increase the production of G-6-PD as well as the phosphogluconate dehydrogenase. 8.4 Metabolism of OTHER Important Sugars A variety of sugars, other than glucose, are vital in vertebrates. The most prominent of them are galactose and fructose and mannose. In addition to glucose, these compounds are the most frequently used sugars in oligosaccharides and polysaccharides. They also provide energy sources. The process that allow these sugars to be transformed into glycolytic intermediates is depicted in the figure 8.16. The process of metabolism of fructose which is an important element of human diet, is described. The sources for fructose are honey, fruit sucrose, sugar, and high fructose corn syrup, which is a low-cost sweetener found in a large range of processed food items and drinks. Best JEE coaching in Guwahati.

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Fructose is second to glucose in terms of sources of carbohydrates in the modern human diet, is able to enter the glycolytic process through two pathways. The liver is where fructose gets transformed into fructose-1 phosphate via fructokinase. When it enters in the glycolytic process, it’s first broken down into dihydroxyacetonephosphate (DHAP) as well as glyceraldehyde via fructose-1-phosphate’s aldolase. DHAP is then converted to glyceraldehyde-3-phosphate by triose phosphate isomerase. Glyceraldehyde-3-phosphate is generated from glyceraldehyde and ATP by glyceraldehyde kinase. KEY CONCEPT The pentose phosphate pathway produces NADPH, ribose-5-phosphate, and the glycolytic intermediates fructose-6-phosphate and glyceraldehyde-3-phosphate.Carbohydrate Metabolism: Other Important Sugars Fructose enters the glycolytic pathway by two routes.Best JEE coaching in Guwahati.

 The liver-cell enzyme fructokinase converts fructose into fructose-1 phosphate which is later divided into DHAP and Glyceraldehyde. In muscle and adipose tissue, fructose is phosphorylated by hexokinase to form the glycolytic intermediate fructose-6-phosphate. Galactose is converted into galactose-1-phosphate, which then reacts with UDP-glucose to form UDP-galactose. UDP-galactose transforms into its epimer, which is UDP-glucose. This is the glycogen synthesizer’s substrate. Mannose is phosphorylated by hexokinase to form mannose-6-phosphate, which is then isomerized to fructose-6-phosphate.Glycogen Metabolism 34 The transformation of fructose-1 phosphate into glycolytic intermediates skips two steps of regulation (the reactions triggered by hexokinase as well as the PFK-1) and, thus in contrast with glucose the entry from fructose to glycolytic pathways is not controlled. 

In adipose and muscle tissue it is converted into the glycolytic intermediate fructose-6-phosphate through the enzyme hexokinase. Since hexokinases possess an insignificant affinity for fructose this reaction is not significant except when the consumption of fructose is high. 8.5 GLYCOGEN METABOLISM Glycogen is the glucose storage form. The synthesis and degrading of glycogen is controlled to ensure that enough glucose is available to meet the body’s energy requirements. The glycogenolysis and glycogenogenesis processes are controlled through three hormonal agents: insulin insulin and epinephrine. Glycogenesis The process of synthesis of glycogen occurs following an eating event, in the event that blood sugar levels become elevated. It is widely known that consumption carbohydrates during a meal is quickly followed by the process of glycogenesis in the liver. Best JEE coaching in Guwahati.

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The process of making glycogen from glucose-6-phosphate requires the following series of reactions. 1. The synthesis of glucose-1-phosphate. The glucose-6-phosphate form is reversed to glucose-1-phosphate through phosphoglucomutase. It is an enzyme that has an phosphoryl group that is attached to a serine reactive residue: 34 CHAPTER 8 Carbohydrate Metabolism enzyme’s phosphoryl group gets converted to glucose-6-phosphate and forms glucose 1,6-bisphosphate. As glucose-1-phosphate develops the phosphoryl group that is that is attached to the C-6 acid is then transferred onto the serine residue of the enzyme. 2. The synthesis of UDP-glucose. Glycosidic bonds are formed as an endogenous process. Derivating the sugar using an excellent leaving group is the driving force that is required for the majority of reaction of sugar transfer. Best JEE coaching in Guwahati.

Because of this, sugar-nucleotide synthesizing is a typical reaction that precedes polymerization and sugar transfer processes. Uridine diphosphate glucose (UDP-glucose) is more reactive than glucose and is more secure in the active sites of enzymes responsible for triggering transfers (referred to known as glycosyl transferases). Because UDP-glucose is composed of two phosphoryl bonds, it’s an extremely reactive molecule. The formation of UDP-glucose, which’s G value is nearly zero it is a reversible reaction that is catalyzed by the pyrophosphorylase of UDP- But, the reaction takes place until it is complete by the pyrophosphate (PPi ) is instantly and irreversibly hydrolyzed through the pyrophosphatase enzyme, resulting in a significant reduction in free energy (G3.35 kJ/mol). 33.5 KJ/mol): (Recall that removing products shifts the equilibrium to the left. This strategy of cellular origin is typical.) 

Synthesis of glycogen using UDP-glucose. The process of synthesising glycogen from UDP-glucose is dependent on two key enzymes. (a) glycogen synthase that catalyzes transfer of the glucosyl glucosyl group of UDP-glucose towards the nonreducing edges of glycogen (Figure 8.17a) as well as (b) amylo-(1,4 1,4) 1,6)-glucosyl transferase (branching enzyme) which forms the (1,6) links to branching in this molecule (Figure 8.17b). Glycogen synthesizing requires a trisaccharide, which is made up consisting of 4 (1,4)-linked glucosyl residues (1,4) linked to glucosyl. The first of these has been linked with a particular Tyrosine-linked residue in the “primer” glycogenin protein. The glycogen chain then gets expanded by the glycogen synthase, a branching enzyme. Large glycogen granules, each consisting of a single highly Glucose-6-phosphate Glucose-1,6-bisphosphateT. Best JEE coaching in Guwahati.