Glycogen is a branched polymer of glucose residues stored in liver and muscle cells. Glycogen phosphorylase catalyzes the phosphorolytic cleavage of glycogen into glucose-1-phosphate during glycogenesis. Pyridoxal phosphate is a cofactor that aids in this reaction. Glycogen synthesis involves the addition of glucose residues from UDP-glucose, catalyzed by glycogen synthase. Both glycogen breakdown and synthesis are regulated by allosteric effectors and phosphorylation to prevent a futile cycle.
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporters are present in all phyla.
This document summarizes sphingolipid metabolism. It discusses that sphingolipids are composed of ceramide and a head group like phosphorylcholine or carbohydrates. Sphingolipid synthesis begins with the formation of ceramide from sphingosine and a fatty acid on the endoplasmic reticulum. Ceramide is then used to synthesize complex sphingolipids like sphingomyelin and glycosphingolipids in the Golgi apparatus. Deficiencies in sphingolipid catabolic enzymes can cause sphingolipidoses, lipid storage disorders that mainly affect the nervous system.
This document discusses glycolipids, which are lipids that contain one or more sugar molecules. Glycolipids are classified as glycosphingolipids, globosides, gangliosides, and sulfatides. Glycosphingolipids contain ceramide and one or more sugars. Gangliosides contain sialic acid and contribute to cell membrane structure and function. Genetic defects that prevent the breakdown of glycolipids cause lipid storage diseases like Gaucher's disease and Tay-Sachs disease, leading to lipid accumulation in tissues and associated symptoms. Laboratory tests can diagnose these conditions by measuring enzyme levels or examining tissues. Some lipid storage diseases can be treated through enzyme replacement therapy.
Glucose transport into cells is mediated by glucose transporter (GLUT) proteins. [1] There are five main GLUT transporters that are involved in glucose transport and each has a distinct tissue distribution and function. [2] GLUT transporters use a flip-flop mechanism to transport glucose across the cell membrane according to the concentration gradient. [3] Insulin regulates glucose transport by stimulating the translocation of GLUT4 and GLUT1 transporters from intracellular vesicles to the cell membrane, increasing the influx of glucose into cells.
Polysaccharide introduction, example, structure, starch, cellulose, chitin those structure and important functions and their presence in plants and animals, polysaccharide types based on functions and their composition , functions of polysaccharides , important images for relevant polysaccharides types, polysaccharide role in plants and animal cells. Starch - structure and functions, cellulose structure and functions, chitin - structure and functions
Proteoglycans are complex macromolecules consisting of a core protein with one or more glycosaminoglycan chains attached. They are found mainly in connective tissues and help modulate cellular development processes. Glycoproteins contain oligosaccharide chains covalently bonded to amino acids on their polypeptide side chains. They are found in cellular membranes and function in cellular recognition. Some examples of glycoproteins discussed are mucins, transferrins, fibrinogen, follicle-stimulating hormone, and erythropoietin.
This document summarizes the glucuronic acid pathway, an alternative oxidative pathway for glucose metabolism. It provides UDP-glucuronic acid, which is used to conjugate bilirubin, steroids, and drugs to make them more water soluble and excretable. The pathway also synthesizes glycosaminoglycans and is involved in vitamin C synthesis in many animals. Key steps include the conversion of glucose-6-phosphate to UDP-glucuronate and the subsequent production of L-gulonate, a precursor for ascorbic acid synthesis. Certain genetic disorders can cause excess excretion of metabolites from this pathway such as L-xylulose in essential pentosuria.
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporters are present in all phyla.
This document summarizes sphingolipid metabolism. It discusses that sphingolipids are composed of ceramide and a head group like phosphorylcholine or carbohydrates. Sphingolipid synthesis begins with the formation of ceramide from sphingosine and a fatty acid on the endoplasmic reticulum. Ceramide is then used to synthesize complex sphingolipids like sphingomyelin and glycosphingolipids in the Golgi apparatus. Deficiencies in sphingolipid catabolic enzymes can cause sphingolipidoses, lipid storage disorders that mainly affect the nervous system.
This document discusses glycolipids, which are lipids that contain one or more sugar molecules. Glycolipids are classified as glycosphingolipids, globosides, gangliosides, and sulfatides. Glycosphingolipids contain ceramide and one or more sugars. Gangliosides contain sialic acid and contribute to cell membrane structure and function. Genetic defects that prevent the breakdown of glycolipids cause lipid storage diseases like Gaucher's disease and Tay-Sachs disease, leading to lipid accumulation in tissues and associated symptoms. Laboratory tests can diagnose these conditions by measuring enzyme levels or examining tissues. Some lipid storage diseases can be treated through enzyme replacement therapy.
Glucose transport into cells is mediated by glucose transporter (GLUT) proteins. [1] There are five main GLUT transporters that are involved in glucose transport and each has a distinct tissue distribution and function. [2] GLUT transporters use a flip-flop mechanism to transport glucose across the cell membrane according to the concentration gradient. [3] Insulin regulates glucose transport by stimulating the translocation of GLUT4 and GLUT1 transporters from intracellular vesicles to the cell membrane, increasing the influx of glucose into cells.
Polysaccharide introduction, example, structure, starch, cellulose, chitin those structure and important functions and their presence in plants and animals, polysaccharide types based on functions and their composition , functions of polysaccharides , important images for relevant polysaccharides types, polysaccharide role in plants and animal cells. Starch - structure and functions, cellulose structure and functions, chitin - structure and functions
Proteoglycans are complex macromolecules consisting of a core protein with one or more glycosaminoglycan chains attached. They are found mainly in connective tissues and help modulate cellular development processes. Glycoproteins contain oligosaccharide chains covalently bonded to amino acids on their polypeptide side chains. They are found in cellular membranes and function in cellular recognition. Some examples of glycoproteins discussed are mucins, transferrins, fibrinogen, follicle-stimulating hormone, and erythropoietin.
This document summarizes the glucuronic acid pathway, an alternative oxidative pathway for glucose metabolism. It provides UDP-glucuronic acid, which is used to conjugate bilirubin, steroids, and drugs to make them more water soluble and excretable. The pathway also synthesizes glycosaminoglycans and is involved in vitamin C synthesis in many animals. Key steps include the conversion of glucose-6-phosphate to UDP-glucuronate and the subsequent production of L-gulonate, a precursor for ascorbic acid synthesis. Certain genetic disorders can cause excess excretion of metabolites from this pathway such as L-xylulose in essential pentosuria.
Heteropolysaccharides are polymers made from two or more types of monosaccharides. They include glycosaminoglycans (GAGs) like hyaluronic acid and chondroitin sulfates, as well as glycoconjugates and mucilages. GAGs are long, unbranched polymers containing uronic acid and amino sugars that form gels and provide structural support to tissues. Common GAGs include hyaluronic acid in joints and vitreous humor, chondroitin sulfate in cartilage, and heparin which is an anticoagulant found in mast cells. Glycoconjugates contain GAGs attached to core proteins, like proteoglycans in the extracellular matrix. M
What is Glycoprotein ?:
Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains.
This process is known as glycosylation.
The carbohydrate is attached to the protein during the following modifications: Co-translational modification & Post-translational modification.
In proteins that have segments extending extracellularly, the extracellular segments are often glycosylated.
Regulation of glycolysis and gluconeogenesisSKYFALL
Regulation of glycolysis and gluconeogenesis is controlled by enzymes and hormones. Key enzymes in glycolysis like phosphofructokinase and pyruvate kinase are regulated by allosteric effectors like ATP, AMP, and citrate to control the pathway. The opposing pathway of gluconeogenesis is regulated by enzymes like fructose-1,6-bisphosphatase and pyruvate carboxylase which have opposite regulation to their glycolytic counterparts. Hormones like insulin promote glycolysis while glucagon stimulates gluconeogenesis to regulate blood glucose levels.
This document summarizes different classes of lipids, including eicosanoids, terpenoids, steroids, and phytosterols. It describes the structures and properties of prostaglandins, leukotrienes, lipoxins, terpenes, carotenoids, dolichol, coenzyme Q, cholesterol, bile acids, phytosterols like sitosterol and stigmasterol. Examples are provided of monoterpenes, sesquiterpenes, diterpenes, and tetraterpenes. The roles of these lipids in biological processes and potential applications are briefly mentioned.
The document discusses two shuttles - the malate-aspartate shuttle and glycerol-phosphate shuttle - that balance redox potential between the cytosol and mitochondria during gluconeogenesis. The malate-aspartate shuttle transports metabolites and NADH between compartments, while the glycerol-phosphate shuttle transports only NADH. Both shuttles are required to balance redox states and transport metabolites lacking dedicated transporters between subcellular locations during gluconeogenesis.
Proteoglycans are protein chains that are covalently bonded at multiple sites to a class of polysaccharides, known as glycosaminoglycans.Glycosaminoglycans constitute 95% of proteins.Proteoglycans are synthesised in RE and transported to GA where they are modified in to various forms.Proteoglycans are major component of ECM and their role is depended on the type of GAGs they associate with.
This document summarizes polysaccharides and glycans. It discusses homopolysaccharides including fructosan, galactosan, and glucosans such as starch and glycogen. Starch is made of amylose and amylopectin and forms helical structures with iodine. Cellulose is composed of beta-glucose units linked by beta-1,4 bonds, forming long straight chains strengthened by hydrogen bonds. Glycosaminoglycans discussed include hyaluronic acid, chondroitin sulfate, keratin sulfate, dermatan sulfate, and heparan sulfate. Proteoglycans are composed of core proteins with covalently linked glycosaminoglycan side chains. They
The document summarizes the hexose monophosphate pathway (HMP pathway), also known as the pentose phosphate pathway. It has three main functions: 1) supply NADPH, 2) convert hexoses to pentoses, and 3) enable complete oxidation of pentoses. NADPH functions as an electron donor in biosynthetic reactions, unlike NADH which generates ATP. The pathway occurs in the cytosol and is important in tissues that synthesize fatty acids and steroids, as it provides the required NADPH. Glucose utilization via this pathway varies between tissues and is higher in liver, adipose tissue, and erythrocytes. Deficiencies in enzymes in this pathway can cause
Polysaccharides are polymers of monosaccharides joined by glycosidic bonds. There are two main types: homopolysaccharides containing only one type of monosaccharide and heteropolysaccharides containing two or more types. Starch and glycogen are examples of homopolysaccharides used for energy storage in plants and animals, respectively. Cellulose, a structural polysaccharide found in plant cell walls, is a linear polymer of glucose monomers joined by beta-1,4 linkages. Gluconeogenesis is the pathway that synthesizes glucose from non-carbohydrate precursors, using both common and unique enzymes compared to glycolysis. Nucleoside diphosphate sugars play a central role in polys
The pentose phosphate pathway, also known as the hexose monophosphate shunt, is an alternative metabolic pathway to glycolysis that occurs in the cytosol. It is a complex pathway that helps generate NADPH for fatty acid synthesis and glutathione for antioxidant activity, as well as synthesizing ribose-5-phosphate for nucleotide and nucleic acid formation. Glucose-6-phosphate enters the pathway and is oxidized through a two-phase process involving dehydrogenation using NADP+ instead of NAD+. Several intermediates are formed and rearranged before regenerating glucose-6-phosphate and glyceraldehyde-3-phosphate to complete the nonoxidative phase. Genetic defects in glucose-6
This document discusses fatty acid synthesis in the body. It begins by defining fatty acids and describing their roles in energy storage and as structural components of membranes. There are three systems for fatty acid synthesis: de novo synthesis in the cytoplasm, chain elongation in mitochondria, and chain elongation in microsomes. De novo synthesis occurs primarily in the liver and adipose tissues, starting from acetyl-CoA derived from glucose. This synthesis takes place in the cytoplasm and requires acetyl-CoA transport from mitochondria via citrate. The document then details the multi-step process of de novo fatty acid synthesis catalyzed by acetyl-CoA carboxylase and fatty acid synthase, and describes regulation of synthesis by products, hormones,
Gluconeogenesis is the process by which glucose is synthesized from non-carbohydrate precursors in the liver and kidneys. It occurs mainly during periods of fasting and involves converting substrates like lactate, glycerol, and certain amino acids into glucose. The pathway overcomes three thermodynamic barriers of glycolysis through smaller successive steps. Regulation occurs through allosteric control of enzymes, hormonal control of fructose 2,6-bisphosphate levels, and transcriptional control of key genes like PEPCK and FOXO1. Together these mechanisms help direct carbon fluxes towards gluconeogenesis or glycolysis based on energy demands.
- Glycoproteins are proteins that contain oligosaccharide chains covalently attached to their polypeptide backbones. They serve important biological roles.
- There are two main classes of glycoproteins: O-linked, where sugars attach to serine or threonine residues, and N-linked, where sugars attach to asparagine residues.
- Diseases can result from defects in glycoprotein biosynthesis, such as I-cell disease caused by a defect in N-linked glycosylation and congenital disorders of glycosylation caused by various defects impacting O-linked or N-linked glycosylation.
Secondary messengers are intracellular signaling molecules that are released within cells in response to extracellular signaling molecules known as first messengers like hormones and neurotransmitters. Common examples include cyclic AMP, inositol trisphosphate, diacylglycerol, and calcium ions. These secondary messengers help amplify and propagate intracellular signals by binding to target proteins and modulating their activity, often through phosphorylation. They allow cells to mount robust physiological responses despite the extracellular signals not directly crossing the cell membrane.
Mucopolysaccharides are gel-like substances found in body cells, mucous secretions, and synovial fluids. Mucopolysaccharidoses are genetic disorders caused by a deficiency of enzymes needed to break down mucopolysaccharides, resulting in their excessive accumulation in body tissues. This can cause skeletal deformities, mental retardation, decreased life expectancy, and other serious physical disorders. Examples of mucopolysaccharidoses include Hurler syndrome, Hunter syndrome, Scheie syndrome, Sanfilippo syndrome, Morquio disease, and Maroteaux-Lamy syndrome. Currently there is no cure for mucopolysaccharide disorders, but enzyme replacement therapy and gene therapy are areas of focus for
Eicosanoids are 20-carbon compounds derived from polyunsaturated fatty acids like arachidonic acid that act as local hormones. They include prostaglandins, thromboxanes, and leukotrienes, which play important roles in inflammation and regulating other physiological processes. They are synthesized through the cyclooxygenase and lipoxygenase pathways and have short lifespans, being quickly degraded. Eicosanoids function through G-protein coupled cell surface receptors and though potent, also have diverse tissue-specific actions.
1. G-proteins bind GTP and control intracellular signaling pathways. They exist in two states - active when bound to GTP and inactive when bound to GDP.
2. G-proteins are tightly regulated by accessory proteins that modulate their cycling between GTP-bound and GDP-bound states.
3. The heterotrimeric G-proteins transmit signals from cell surface receptors to enzymes and channels. They are stimulated by receptors, act on effectors, and are regulated by nucleotide exchange and hydrolysis.
Glycogenesis is the formation of glycogen from glucose, which occurs when glucose and ATP levels are high. Glycogenolysis is the breakdown of glycogen into glucose, which is stimulated by glucagon and epinephrine when blood glucose levels drop. Together, glycogenesis and glycogenolysis regulate glucose concentrations by converting excess glucose to glycogen for storage and releasing glucose from glycogen as needed.
Glycogen is the storage form of carbohydrates in the human body, primarily in the liver and muscle. The liver stores glycogen to provide glucose to maintain blood sugar levels during periods of starvation. Muscle stores glycogen to act as a fuel reserve for muscle contraction, becoming depleted during prolonged exercise.
Heteropolysaccharides are polymers made from two or more types of monosaccharides. They include glycosaminoglycans (GAGs) like hyaluronic acid and chondroitin sulfates, as well as glycoconjugates and mucilages. GAGs are long, unbranched polymers containing uronic acid and amino sugars that form gels and provide structural support to tissues. Common GAGs include hyaluronic acid in joints and vitreous humor, chondroitin sulfate in cartilage, and heparin which is an anticoagulant found in mast cells. Glycoconjugates contain GAGs attached to core proteins, like proteoglycans in the extracellular matrix. M
What is Glycoprotein ?:
Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains.
This process is known as glycosylation.
The carbohydrate is attached to the protein during the following modifications: Co-translational modification & Post-translational modification.
In proteins that have segments extending extracellularly, the extracellular segments are often glycosylated.
Regulation of glycolysis and gluconeogenesisSKYFALL
Regulation of glycolysis and gluconeogenesis is controlled by enzymes and hormones. Key enzymes in glycolysis like phosphofructokinase and pyruvate kinase are regulated by allosteric effectors like ATP, AMP, and citrate to control the pathway. The opposing pathway of gluconeogenesis is regulated by enzymes like fructose-1,6-bisphosphatase and pyruvate carboxylase which have opposite regulation to their glycolytic counterparts. Hormones like insulin promote glycolysis while glucagon stimulates gluconeogenesis to regulate blood glucose levels.
This document summarizes different classes of lipids, including eicosanoids, terpenoids, steroids, and phytosterols. It describes the structures and properties of prostaglandins, leukotrienes, lipoxins, terpenes, carotenoids, dolichol, coenzyme Q, cholesterol, bile acids, phytosterols like sitosterol and stigmasterol. Examples are provided of monoterpenes, sesquiterpenes, diterpenes, and tetraterpenes. The roles of these lipids in biological processes and potential applications are briefly mentioned.
The document discusses two shuttles - the malate-aspartate shuttle and glycerol-phosphate shuttle - that balance redox potential between the cytosol and mitochondria during gluconeogenesis. The malate-aspartate shuttle transports metabolites and NADH between compartments, while the glycerol-phosphate shuttle transports only NADH. Both shuttles are required to balance redox states and transport metabolites lacking dedicated transporters between subcellular locations during gluconeogenesis.
Proteoglycans are protein chains that are covalently bonded at multiple sites to a class of polysaccharides, known as glycosaminoglycans.Glycosaminoglycans constitute 95% of proteins.Proteoglycans are synthesised in RE and transported to GA where they are modified in to various forms.Proteoglycans are major component of ECM and their role is depended on the type of GAGs they associate with.
This document summarizes polysaccharides and glycans. It discusses homopolysaccharides including fructosan, galactosan, and glucosans such as starch and glycogen. Starch is made of amylose and amylopectin and forms helical structures with iodine. Cellulose is composed of beta-glucose units linked by beta-1,4 bonds, forming long straight chains strengthened by hydrogen bonds. Glycosaminoglycans discussed include hyaluronic acid, chondroitin sulfate, keratin sulfate, dermatan sulfate, and heparan sulfate. Proteoglycans are composed of core proteins with covalently linked glycosaminoglycan side chains. They
The document summarizes the hexose monophosphate pathway (HMP pathway), also known as the pentose phosphate pathway. It has three main functions: 1) supply NADPH, 2) convert hexoses to pentoses, and 3) enable complete oxidation of pentoses. NADPH functions as an electron donor in biosynthetic reactions, unlike NADH which generates ATP. The pathway occurs in the cytosol and is important in tissues that synthesize fatty acids and steroids, as it provides the required NADPH. Glucose utilization via this pathway varies between tissues and is higher in liver, adipose tissue, and erythrocytes. Deficiencies in enzymes in this pathway can cause
Polysaccharides are polymers of monosaccharides joined by glycosidic bonds. There are two main types: homopolysaccharides containing only one type of monosaccharide and heteropolysaccharides containing two or more types. Starch and glycogen are examples of homopolysaccharides used for energy storage in plants and animals, respectively. Cellulose, a structural polysaccharide found in plant cell walls, is a linear polymer of glucose monomers joined by beta-1,4 linkages. Gluconeogenesis is the pathway that synthesizes glucose from non-carbohydrate precursors, using both common and unique enzymes compared to glycolysis. Nucleoside diphosphate sugars play a central role in polys
The pentose phosphate pathway, also known as the hexose monophosphate shunt, is an alternative metabolic pathway to glycolysis that occurs in the cytosol. It is a complex pathway that helps generate NADPH for fatty acid synthesis and glutathione for antioxidant activity, as well as synthesizing ribose-5-phosphate for nucleotide and nucleic acid formation. Glucose-6-phosphate enters the pathway and is oxidized through a two-phase process involving dehydrogenation using NADP+ instead of NAD+. Several intermediates are formed and rearranged before regenerating glucose-6-phosphate and glyceraldehyde-3-phosphate to complete the nonoxidative phase. Genetic defects in glucose-6
This document discusses fatty acid synthesis in the body. It begins by defining fatty acids and describing their roles in energy storage and as structural components of membranes. There are three systems for fatty acid synthesis: de novo synthesis in the cytoplasm, chain elongation in mitochondria, and chain elongation in microsomes. De novo synthesis occurs primarily in the liver and adipose tissues, starting from acetyl-CoA derived from glucose. This synthesis takes place in the cytoplasm and requires acetyl-CoA transport from mitochondria via citrate. The document then details the multi-step process of de novo fatty acid synthesis catalyzed by acetyl-CoA carboxylase and fatty acid synthase, and describes regulation of synthesis by products, hormones,
Gluconeogenesis is the process by which glucose is synthesized from non-carbohydrate precursors in the liver and kidneys. It occurs mainly during periods of fasting and involves converting substrates like lactate, glycerol, and certain amino acids into glucose. The pathway overcomes three thermodynamic barriers of glycolysis through smaller successive steps. Regulation occurs through allosteric control of enzymes, hormonal control of fructose 2,6-bisphosphate levels, and transcriptional control of key genes like PEPCK and FOXO1. Together these mechanisms help direct carbon fluxes towards gluconeogenesis or glycolysis based on energy demands.
- Glycoproteins are proteins that contain oligosaccharide chains covalently attached to their polypeptide backbones. They serve important biological roles.
- There are two main classes of glycoproteins: O-linked, where sugars attach to serine or threonine residues, and N-linked, where sugars attach to asparagine residues.
- Diseases can result from defects in glycoprotein biosynthesis, such as I-cell disease caused by a defect in N-linked glycosylation and congenital disorders of glycosylation caused by various defects impacting O-linked or N-linked glycosylation.
Secondary messengers are intracellular signaling molecules that are released within cells in response to extracellular signaling molecules known as first messengers like hormones and neurotransmitters. Common examples include cyclic AMP, inositol trisphosphate, diacylglycerol, and calcium ions. These secondary messengers help amplify and propagate intracellular signals by binding to target proteins and modulating their activity, often through phosphorylation. They allow cells to mount robust physiological responses despite the extracellular signals not directly crossing the cell membrane.
Mucopolysaccharides are gel-like substances found in body cells, mucous secretions, and synovial fluids. Mucopolysaccharidoses are genetic disorders caused by a deficiency of enzymes needed to break down mucopolysaccharides, resulting in their excessive accumulation in body tissues. This can cause skeletal deformities, mental retardation, decreased life expectancy, and other serious physical disorders. Examples of mucopolysaccharidoses include Hurler syndrome, Hunter syndrome, Scheie syndrome, Sanfilippo syndrome, Morquio disease, and Maroteaux-Lamy syndrome. Currently there is no cure for mucopolysaccharide disorders, but enzyme replacement therapy and gene therapy are areas of focus for
Eicosanoids are 20-carbon compounds derived from polyunsaturated fatty acids like arachidonic acid that act as local hormones. They include prostaglandins, thromboxanes, and leukotrienes, which play important roles in inflammation and regulating other physiological processes. They are synthesized through the cyclooxygenase and lipoxygenase pathways and have short lifespans, being quickly degraded. Eicosanoids function through G-protein coupled cell surface receptors and though potent, also have diverse tissue-specific actions.
1. G-proteins bind GTP and control intracellular signaling pathways. They exist in two states - active when bound to GTP and inactive when bound to GDP.
2. G-proteins are tightly regulated by accessory proteins that modulate their cycling between GTP-bound and GDP-bound states.
3. The heterotrimeric G-proteins transmit signals from cell surface receptors to enzymes and channels. They are stimulated by receptors, act on effectors, and are regulated by nucleotide exchange and hydrolysis.
Glycogenesis is the formation of glycogen from glucose, which occurs when glucose and ATP levels are high. Glycogenolysis is the breakdown of glycogen into glucose, which is stimulated by glucagon and epinephrine when blood glucose levels drop. Together, glycogenesis and glycogenolysis regulate glucose concentrations by converting excess glucose to glycogen for storage and releasing glucose from glycogen as needed.
Glycogen is the storage form of carbohydrates in the human body, primarily in the liver and muscle. The liver stores glycogen to provide glucose to maintain blood sugar levels during periods of starvation. Muscle stores glycogen to act as a fuel reserve for muscle contraction, becoming depleted during prolonged exercise.
This document summarizes several glycogen storage diseases caused by deficiencies in enzymes involved in glycogen synthesis and breakdown. Key points include: glycogen storage diseases are inherited disorders characterized by abnormal glycogen deposition; deficiencies in enzymes like glucose-6-phosphatase and acid maltase can cause hypoglycemia, lactic acidosis, hyperlipidemia, and other issues; the organs and severity of symptoms vary depending on the specific enzyme deficiency.
Glycogen is the storage from of glucose. The metabolism of glycogen both as glycogenolysis, breakdown of glycogen, and glycogenesis, formation of glycogen along with their regulation is briefed in the slides.
Glycogen is the major storage form of glucose found mainly in the liver and skeletal muscles. It is formed from glucose through glycogenesis and broken down into glucose through glycogenolysis. These pathways are regulated by enzymes like glycogen synthase and glycogen phosphorylase in response to hormones like insulin and glucagon to maintain blood glucose levels. Deficiencies in enzymes of glycogen metabolism can result in glycogen storage diseases characterized by hypoglycemia, hepatomegaly and other symptoms.
1. Glycogen is a branched polymer of glucose that serves as the major storage form of carbohydrates in animals. It provides a readily available source of glucose for glycolysis in muscle and liver.
2. Glycogen storage diseases are a group of inherited disorders characterized by deficient glycogen metabolism, leading to liver and muscle issues and sometimes early death.
3. Glycogen synthesis (glycogenesis) involves the enzyme UDP-glucose and occurs mainly in liver and muscle. Glycogen breakdown (glycogenolysis) is catalyzed by glycogen phosphorylase and converts glycogen to glucose-1-phosphate rather than being the reverse of glycogenesis.
Glycogen is the storage form of glucose found in the liver and muscles. It consists of glucose monomers linked together by glycosidic bonds to form a branched polymer. Glycogen serves as a readily available source of glucose through the processes of glycogenolysis and glycogenesis. Glycogenolysis involves the breakdown of glycogen into glucose-1-phosphate through the actions of phosphorylase, phosphoglucomutase, and glucose-6-phosphatase. Glycogenesis is the synthesis of glycogen from glucose-6-phosphate utilizing glycogen synthase and branching enzyme. The activities of these enzymes are regulated by hormonal signals and allosteric effectors to ensure coordinated anabolism and catabol
GLYCOGENOLYSIS & REGULATION OF GLYCOGEN METABOLISMYESANNA
- Glycogenolysis is the degradation of glycogen stores in the liver and muscle into glucose. It is carried out by independent cytosolic enzymes.
- Glycogen phosphorylase breaks alpha-1,4 glycosidic bonds in glycogen, producing glucose-1-phosphate. A debranching enzyme then breaks alpha-1,6 bonds to fully degrade glycogen.
- Glucose-1-phosphate is converted to glucose-6-phosphate which can be further converted to glucose by glucose-6-phosphatase in the liver, releasing it into circulation. Muscle lacks this enzyme and uses its glucose-6-phosphate in glycolysis.
- Glycogen metabolism is regulated by hormones like
The synthesis of glycogen from glucose (glycogenesis) involves multiple enzymatic steps that takes place in the cytosol. Glucose is first converted to glucose-6-phosphate by hexokinase or glucokinase in muscle and liver respectively. It is then converted to UDP-glucose which acts as the donor of glucose units. A glycogen primer, initiated by the enzyme glycogen synthase, is required to begin glycogen synthesis. Glycogen is then elongated through alpha-1,4 glycosidic linkages by glycogen synthase and branched through alpha-1,6 linkages by the branching enzyme glucosyltransferase. This leads to the formation of the branched glyc
Glycogen is a branched polymer of glucose residues that serves as a storage form of glucose. It is composed mainly of α-1,4 glycosidic linkages with branches every tenth residue by α-1,6 linkages. Glycogen is found primarily in liver and muscle cells bound in granules and provides a readily available source of glucose through breakdown. Glycogen synthesis utilizes UDP-glucose and glycogenin to initiate polymer formation, while breakdown is catalyzed by phosphorylase releasing glucose-1-phosphate and other enzymes are needed to further process the glucose for energy production.
Glycogen is a branched polymer of glucose that serves as the main energy storage molecule in animal cells. It is broken down into glucose-6-phosphate through glycogenolysis, which occurs primarily in the liver and skeletal muscle in response to hormones like glucagon and epinephrine. Glycogenolysis involves three key steps: 1) glycogen phosphorylase cleaves α-1,4 glycosidic linkages via phosphorolysis to produce glucose-1-phosphate, 2) glycogen debranching enzyme cleaves α-1,6 linkages in branches, and 3) phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate. This glucose-6-phosphate
GLYCOGEN METABOLISM IN ANIMALS FOR VETS.pdfTatendaMageja
Glycogen is the storage form of glucose in mammalian cells. It is synthesized from glucose in the liver and muscles, and broken down to release glucose during periods of fasting or high energy demand. Glycogen metabolism is regulated by hormones like insulin and glucagon through interconversion of key enzymes between active and inactive forms. When blood glucose levels rise after a meal, insulin stimulates glycogen synthesis in liver and muscle by activating glycogen synthase and inhibiting glycogen phosphorylase. During fasting, glucagon and epinephrine stimulate glycogen breakdown in liver through cAMP signaling and glycogen phosphorylase activation to maintain blood glucose levels.
Gluconeogenesis and glycolysis share many of the same enzymes but operate in opposite directions. Three irreversible steps in glycolysis - those catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase - must be bypassed in gluconeogenesis. This is accomplished through different enzymes that catalyze reversible reactions, such as glucose-6-phosphatase and fructose-1,6-bisphosphatase. Regulation ensures that glycolysis and gluconeogenesis do not operate simultaneously, which would waste energy. Key control points include allosteric regulation by adenine nucleotides and hormonal stimulation of cAMP and protein phosphorylation.
Gluconeogenesis and glycolysis share many enzymes but differ in directionality. Three irreversible glycolysis reactions - involving hexokinase, phosphofructokinase, and pyruvate kinase - are bypassed in gluconeogenesis through different enzymes. Gluconeogenesis is regulated by substrates, enzymes, and hormones to prevent wasteful cycling between the two pathways.
Gluconeogenesis occurs mainly in the liver to synthesize glucose from non-carbohydrate precursors like lactate, glycerol, and glucogenic amino acids. It utilizes the same enzymes as glycolysis but must bypass three irreversible steps. The bypass reactions include glucose-6-phosphatase and fructose-1,6-bisphosphatase hydrolyzing high-energy intermediates, and a two-step process involving pyruvate carboxylase and PEP carboxykinase to bypass pyruvate kinase. Gluconeogenesis and glycolysis are reciprocally regulated to prevent a wasteful futile cycle between the two pathways.
Glycogen is the storage form of glucose in animals. It is made up of glucose units bonded together and stored primarily in the liver and muscle cells. Glycogen synthesis involves adding glucose-1-phosphate units to glycogen polymers, regulated by glycogen synthase. Glycogen breakdown releases glucose-1-phosphate units using glycogen phosphorylase. This process provides a quick source of glucose for energy. The liver stores glycogen to regulate blood glucose levels, while muscle glycogen provides energy during exercise without releasing glucose into the blood.
1. Glycogen is an energy storage molecule made of glucose units that is stored mainly in the liver and muscle.
2. Glycogen synthesis (glycogenesis) converts glucose into glycogen through a series of enzymatic reactions, while glycogen breakdown (glycogenolysis) converts glycogen back into glucose.
3. Liver glycogen breakdown provides glucose to the bloodstream, while muscle glycogen breakdown provides glucose locally without releasing it into circulation.
The document discusses glycogen degradation (glycogenolysis). It describes the four enzymes involved - phosphorylase, debranching enzyme, phosphoglucomutase, and glucose-6-phosphatase. Phosphorylase breaks down glycogen into glucose-1-phosphate. The debranching enzyme and phosphorylase work together to further degrade glycogen. Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate which can then be used for energy or converted to glucose by glucose-6-phosphatase in the liver. The pathway provides glucose between meals and for anaerobic activity.
Gluconeogenesis is the process by which glucose is synthesized from non-carbohydrate precursors in the liver and kidneys. It occurs mainly in the liver and helps prevent hypoglycemia during fasting. While some of the same enzymes are used in both gluconeogenesis and glycolysis, three irreversible glycolysis reactions must be bypassed. The document provides details on the enzymes and reactions involved in bypassing these steps, including pyruvate carboxylase and PEP carboxykinase. Regulation ensures that gluconeogenesis and glycolysis do not operate simultaneously to avoid an energy-wasting cycle.
Complete Set of Metabolism of Carbohydrate in that second chapter, glycolysis.
This presentation covers complete glycolysis pathway with step wise animated reactions and it includes clinical aspects also. This presentation is good for MBBS students.
The document summarizes key aspects of the hexose monophosphate pathway (HMP pathway or pentose phosphate pathway). It describes the pathway's location in the cytosol and key tissues where it is active. The oxidative and non-oxidative phases of the pathway and their reactions are outlined. Regulation of the pathway by NADPH concentration is mentioned. The significance of the pathway is that it generates pentoses and NADPH, which is important for biosynthesis and antioxidant reactions. Deficiencies in the pathway can cause hemolytic anemia.
Glycolysis is the pathway by which cells break down glucose to extract energy. Glucose first undergoes phosphorylation by hexokinase to form glucose-6-phosphate. A series of enzymatic reactions then convert glucose-6-phosphate through intermediates like fructose-6-phosphate and glyceraldehyde-3-phosphate, extracting energy in the form of ATP. Key steps include substrate-level phosphorylation by phosphofructokinase-1 and oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, reducing NAD+ to NADH. The pathway ultimately forms two pyruvate molecules from each glucose.
glucose- 6-phosphatase
glucose-6- phosphate
The document discusses glycogen metabolism and gluconeogenesis. It provides details on:
Fructose -6- phosphate
1) Glycogen synthesis (glycogenesis) and breakdown (glycogenolysis) pathways in the liver and muscle. Key enzymes involved include glycogen synthase, glycogen phosphorylase and debranching enzyme.
Fructose-1,6-bisphosphatase
2) Regulation of glycogen metabolism by hormones like insulin and glucagon via covalent modification of glycogen synthase and phosphorylase.
Fructose-1,6-bisphosphate
Examville.com is a website that provides online practice tests, live classes, tutoring, study guides, Q&A, and premium content to help students prepare for exams. The document then discusses various topics related to carbohydrate metabolism including glycogen metabolism, gluconeogenesis, the sources and pathways involved in glucose formation, and regulation of glycolysis and gluconeogenesis. It also covers glycogen storage and breakdown, the enzymes involved, and types of glycogen storage diseases.
Examville.com is a website that provides online practice tests, live classes, tutoring, study guides, Q&A, and premium content to help students prepare for exams. The document then discusses various topics related to carbohydrate metabolism including glycogen metabolism, gluconeogenesis, glycolysis, and glycogen storage diseases. It provides details on the pathways and regulation of glucose synthesis and breakdown in the body.
1) Glycolysis breaks down glucose to pyruvate, generating a small amount of ATP. Key enzymes include hexokinase, phosphofructokinase, and pyruvate kinase.
2) Pyruvate is oxidized to acetyl-CoA in mitochondria by the pyruvate dehydrogenase complex, producing NADH.
3) Acetyl-CoA then enters the citric acid cycle, where it is oxidized to carbon dioxide, generating more NADH and FADH2. This fuels the electron transport chain to produce large amounts of ATP through oxidative phosphorylation.
1. Glycolysis breaks down glucose into pyruvate, producing a small amount of ATP. Pyruvate can then enter the mitochondria for further processing.
2. In the mitochondria, pyruvate is converted into acetyl-CoA by the pyruvate dehydrogenase complex, producing NADH.
3. Acetyl-CoA then enters the citric acid cycle, where it is further oxidized, producing more NADH and FADH2. The electrons from these are transferred to the electron transport chain to produce large amounts of ATP through oxidative phosphorylation.
Glycogenolysis is the breakdown of glycogen into glucose-1-phosphate. It occurs in three steps:
1) Phosphorolysis by glycogen phosphorylase cleaves α-1,4 glycosidic linkages, producing glucose-1-phosphate until four glucose residues remain.
2) A debranching enzyme removes these four residue branches through two activities, producing linear chains of glucose residues.
3) Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate, which can then enter glycolysis to produce energy or be released as free glucose from the liver. Glycogenolysis is regulated by allosteric effectors, hormones like glucagon and
A pneumothorax is air in the pleural cavity caused by a tear in the visceral or parietal pleura. On a CXR, it appears as a white line parallel to the chest wall with no lung markings beyond it. A simple pneumothorax has no mediastinal shift, while a tension pneumothorax causes the mediastinum to shift away from the affected side. Causes include spontaneous rupture of an apical bleb, trauma from rib fractures, or pre-existing lung abnormalities.
The document summarizes the structure and function of F1Fo ATP synthase, a membrane-bound enzyme that catalyzes ATP synthesis using an electrochemical proton gradient. It consists of two main components, F1, which protrudes into the mitochondrial matrix and contains the catalytic sites, and Fo, which forms a proton channel embedded in the membrane. During ATP synthesis, protons flow through the Fo channel, causing the central stalk to rotate and drive conformational changes in the F1 catalytic sites that catalyze ATP formation from ADP and phosphate. The rotation mechanism and roles of key subunits like c and a are described.
The Pyruvate Dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA and includes three enzymes: E1, E2, and E3. E1 uses thiamine pyrophosphate to oxidize pyruvate and transfer the acetyl group to E2. Lipoic acid covalently attached to E2 carries the acetyl group to E3, where it is transferred to CoA to form acetyl-CoA. Electrons are transferred through the complex to NAD+ to form NADH. The complex is regulated by phosphorylation/dephosphorylation of E1 and by product inhibition by NADH and acetyl-CoA. Acetyl-CoA produced
The pentose phosphate pathway generates NADPH and pentose sugars. Glucose-6-phosphate enters the pathway and is oxidized by glucose-6-phosphate dehydrogenase, producing 6-phosphogluconolactone. This is hydrolyzed to 6-phosphogluconate by 6-phosphogluconolactonase. 6-Phosphogluconate dehydrogenase further oxidizes this to ribulose-5-phosphate, producing NADPH. Ribulose-5-phosphate can be converted to other 5-carbon sugars like ribose-5-phosphate. Transketolase and transaldolase reactions interconvert pentose and triose phosphates to regenerate ribulose
Glycogen is a branched polymer of glucose residues stored in liver and muscle cells. Glycogen phosphorylase catalyzes the phosphorolytic cleavage of glycogen into glucose-1-phosphate. An inhibitor of glycogen phosphorylase would be a suitable treatment for diabetes by decreasing glycogen breakdown and lowering blood glucose levels. Glycogen synthesis utilizes UDP-glucose to add glucose residues via glycogen synthase. Glycogen phosphorylase and glycogen synthase activities are regulated by allosteric effectors and phosphorylation to prevent futile cycling between glycogen breakdown and synthesis.
This document discusses various causes of cell injury and death, including oxygen deprivation, physical agents, chemicals, infectious agents, immune reactions, genetic defects, and nutritional imbalances. It describes the morphological changes that occur in reversible cell injury, including swelling and fatty change, as well as the changes that characterize irreversible injury or necrosis, such as increased eosinophilia, loss of structure, and membrane breakdown. Different patterns of tissue necrosis are also outlined, such as coagulative, liquefactive, gangrenous, and caseous necrosis.
This document discusses cell injury and cell death. It notes that cells have a normal steady state of homeostasis but stress can force adaptation or injury. Cell injury can be reversible or irreversible, depending on the severity and duration of the stress. Irreversible injury leads to cell death. Mechanisms of injury include damage to membranes, respiration, protein synthesis, and DNA. Causes include hypoxia, free radicals, chemicals, infections, and physical or immunological stresses. Reversible injury disrupts mitochondria and ATP production, while irreversible injury severely damages membranes and organelles. The morphology of injury progresses from reversible changes like swelling to irreversible changes like membrane breaks and nuclear fragmentation. Types of cell death include apoptosis and various forms
Edema and haemorrhage were presented. Edema is the abnormal accumulation of fluid in tissues, which can be localized or generalized. It can be transudate or exudate depending on protein content. Edema fluid can be pitting or non-pitting. Haemorrhage is bleeding which can be arterial, venous, or capillary based on characteristics. It can be primary, reactionary, or secondary depending on timing from injury. The presentation discussed various types and causes of edema and haemorrhage.
1) Shock is defined as a state of profound and widespread reduction in effective tissue perfusion that can lead to cellular injury and death if prolonged.
2) Shock is classified into four main types: hypovolemic, cardiogenic, obstructive, and distributive.
3) Septic shock is the most common cause of death in ICUs and a major form of distributive shock characterized by loss of vasomotor tone and peripheral vasodilation.
1) Shock is defined as a state of profound and widespread reduction in effective tissue perfusion that can lead to cellular injury and death if prolonged.
2) Shock is classified into four main types: hypovolemic, cardiogenic, obstructive, and distributive.
3) Septic shock is the most common cause of death in ICUs and a major form of distributive shock characterized by loss of vasomotor tone and peripheral vasodilation.
This document provides lecture notes for health science students on medical biochemistry. It is divided into six units covering enzymes, carbohydrate metabolism, integrative metabolism and bioenergetics, lipid metabolism, amino acids and proteins, and vitamins and coenzymes. The notes were produced in 2004 in collaboration between Ethiopian universities and ministries with funding from USAID to provide educational materials for health care workers and students.
Black's Medical Dictionary is a comprehensive medical reference work now in its 41st edition. It provides concise definitions and explanations of medical terms in a format that is accessible to both medical professionals and laypeople. The dictionary aims to concisely summarize important medical information and concepts in a way that is clear and understandable. It contains entries for thousands of medical terms organized alphabetically as well as appendices covering topics like basic first aid, medical tests and procedures, vitamins, and health organizations.
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
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A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
2. Glycogen is a polymer of glucose residues linked by
α(14) glycosidic bonds, mainly
α(16) glycosidic bonds, at branch points.
Glycogen chains & branches are longer than shown.
Glucose is stored as glycogen predominantly in liver and
muscle cells.
H O
OH
H
OHH
OH
CH2OH
H
O H
H
OHH
OH
CH2OH
H
O
HH H O
O
H
OHH
OH
CH2
H
H H O
H
OHH
OH
CH2OH
H
OH
HH O
O
H
OHH
OH
CH2OH
H
O
H
O
1 4
6
H O
H
OHH
OH
CH2OH
H
H H O
H
OHH
OH
CH2OH
H
H
O
1
OH
3
4
5
2
glycogen
3. Glycogen Phosphorylase catalyzes phosphorolytic
cleavage of the α(14) glycosidic linkages of glycogen,
releasing glucose-1-phosphate as reaction product.
glycogen(nresidues)
+ Pi
glycogen (n–1residues)
+ glucose-1-phosphate
This phosphorolysis may be compared to hydrolysis:
Hydrolysis: R-O-R' + HOH R-OH + R'-OH
Phosphorolysis: R-O-R' + HO-PO3
2-
R-OH + R'-O-PO3
2-
glucose-1-phosphate
H O
OH
H
OHH
OH
CH2OH
H
OPO3
2−
H
Glycogen catabolism
(breakdown):
4. Pyridoxal phosphate
(PLP), a derivative of
vitamin B6
, serves as
prosthetic group for
Glycogen Phosphorylase.
pyridoxal phosphate (PLP)
N
H
C
O
P
O−
O
O
OH
CH3
C
H O
−
+
H2
5. Pyridoxal phosphate (PLP) is held at the active site by a
Schiff base linkage, formed by reaction of the aldehyde of
PLP with the ε-amino group of a lysine residue.
In contrast to its role in other enzymes, the phosphate of
PLP is involved in acid/base catalysis by Phosphorylase.
N
H
C
O
P
O−
O
O
O−
CH3
HC
−
+
H2
N
(CH2)4
Enz
H
+
Enzyme (Lys)-PLP Schiff base
lysine
6. The Pi substrate binds
between the phosphate of
PLP and the glycosidic O
linking the terminal glucose
residue of the glycogen.
N
H
C
O
P
O−
O
O
O−
CH3
HC
−
+
H2
N
(CH2)4
Enz
H
+
Enzyme (Lys)-PLP Schiff base
After the phosphate substrate donates H+
during cleavage of
the glycosidic bond, it receives H+
from the phosphate
moiety of PLP.
PLP then takes back the H+
as the phosphate O attacks C1 of
the cleaved glucose to yield glucose-1-phosphate.
7. A glucose analog, N-acetylglucosamine (GlcNAc), is
adjacent to pyridoxal phosphate at the active site in the
crystal structure shown.
Glycogen
Phosphorylase:
a homodimeric
enzyme, subject to
allosteric control.
It transitions between
“relaxed” (active) &
“tense” (inhibited)
conformations.
Diagram comparing
relaxed and tense
conformations.
PLP
PLP
GlcNAc
GlcNAc
inhibitor
Human Liver
Glycogen Phosphorylase PDB 1EM6
8. Question: Why would an inhibitor of Glycogen
Phosphorylase be a suitable treatment for diabetes?
A class of drugs
developed for treating
the hyperglycemia of
diabetes (chloroindole-
carboxamides), inhibit
liver Phosphorylase
allosterically.
These inhibitors bind
at the dimer interface,
stabilizing the inactive
(tense) conformation.
PLP
PLP
GlcNAc
GlcNAc
inhibitor
Human Liver
Glycogen Phosphorylase PDB 1EM6
9. A glycogen storage site on the surface of the
Phosphorylase enzyme binds the glycogen particle.
Given the distance between storage & active sites,
Phosphorylase can cleave α(14) linkages only to
within 4 residues of an α(16) branch point.
This is called a "limit branch".
Explore the structure of muscle Glycogen
Phosphorylase with Chime.
10. Debranching enzyme has 2 independent active sites,
consisting of residues in different segments of a single
polypeptide chain:
The transferase of the debranching enzyme
transfers 3 glucose residues from a 4-residue limit
branch to the end of another branch, diminishing the
limit branch to a single glucose residue.
The α(16) glucosidase moiety of the debranching
enzyme then catalyzes hydrolysis of the α(16)
linkage, yielding free glucose. This is a minor
fraction of glucose released from glycogen.
View an animation
The major product of glycogen breakdown is
glucose-1-phosphate, from Phosphorylase activity.
11. Phosphoglucomutase catalyzes the reversible reaction:
glucose-1-phosphate glucose-6-phosphate
A serine OH at the active site donates & accepts Pi.
The bisphosphate is not released.
Phosphoglycerate Mutase has a similar mechanism, but
instead uses His for Pi transfer.
glucose-1-phosphate glucose-6-phosphate
H O
OH
H
OHH
OH
CH2OH
H
OPO3
2−
H H O
OH
H
OHH
OH
CH2OPO3
2−
H
OH
HH O
OH
H
OHH
OH
CH2OPO3
2−
H
OPO3
2−
H
Enzyme-Ser-OPO3
2−
Enzyme-Ser-OPO3
2−
Enzyme-Ser-OH
12. Glucose-6-phosphate may enter Glycolysis or (mainly in
liver) be dephosphorylated for release to the blood.
Liver Glucose-6-phosphatase catalyzes the following,
essential to the liver's role in maintaining blood glucose:
glucose-6-phosphate + H2
O glucose + Pi
Most other tissues lack this enzyme.
Glycogen Glucose
Hexokinase or Glucokinase
Glucose-6-Pase
Glucose-1-P Glucose-6-P Glucose + Pi
Glycolysis
Pathway
Pyruvate
Glucose metabolism in liver.
13. Uridine diphosphate glucose (UDP-glucose) is the
immediate precursor for glycogen synthesis.
As glucose residues are added to glycogen, UDP-glucose
is the substrate and UDP is released as a reaction product.
Nucleotide diphosphate sugars are precursors also for
synthesis of other complex carbohydrates, including
oligosaccharide chains of glycoproteins, etc.
O
O
OHOH
HH
H
CH2
H
HN
N
O
O
OP
O
O−
P
O
O−
H O
OH
H
OHH
OH
CH2OH
H
O
H
UDP-glucose
Glycogen
synthesis
15. UDP-glucose is formed from glucose-1-phosphate:
glucose-1-phosphate + UTP UDP-glucose + PPi
PPi
+ H2
O 2 Pi
Overall:
glucose-1-phosphate + UTP UDP-glucose + 2 Pi
Spontaneous hydrolysis of the ~P bond in PPi
(P~P)
drives the overall reaction.
Cleavage of PPi
is the only energy cost for glycogen
synthesis (one ~P bond per glucose residue).
16. Glycogenin initiates glycogen synthesis.
Glycogenin is an enzyme that catalyzes attachment of a
glucose molecule to one of its own tyrosine residues.
Glycogenin is a dimer, and evidence indicates that the
2 copies of the enzyme glucosylate one another.
Tyr− active site
active site −Tyr
Glycogenin dimer
17. A glycosidic bond is formed between the anomeric C1 of
the glucose moiety derived from UDP-glucose and the
hydroxyl oxygen of a tyrosine side-chain of Glycogenin.
UDP is released as a product.
H O
OH
H
OHH
OH
CH2OH
H
O H
H
OHH
OH
CH2OH
H
O
HH
C
CH
NH
C
H2
O
O
H O
OH
H
OHH
OH
CH2OH
H
H
C
CH
NH
C
H2
O
O
1
5
4
3 2
6
H O
OH
H
OHH
OH
CH2OH
H
H
O
1
5
4
3 2
6
P O P O Uridine
O
O−
O
O−
C
CH
NH
C
H2
HO
O
tyrosine residue
of Glycogenin
O-linked
glucose
residue
+ UDP
UDP-glucose
18. Glycogenin then catalyzes glucosylation at C4 of the
attached glucose (UDP-glucose again the donor), to yield an
O-linked disaccharide with α(1→4) glycosidic linkage.
This is repeated until a short linear glucose polymer with
α(1→4) glycosidic linkages is built up on Glycogenin.
H O
OH
H
OHH
OH
CH2OH
H
O H
H
OHH
OH
CH2OH
H
O
HH
C
CH
NH
C
H2
O
O
H O
OH
H
OHH
OH
CH2OH
H
H
C
CH
NH
C
H2
O
O
1
5
4
3 2
6
UDP-glucose
O-linked
glucose
residue
α(14)
linkage
+ UDP
+ UDP
19. Answer: Most of the Glycogenin is found associated
with glycogen particles (branched glycogen chains)
in the cytoplasm.
Glycogen Synthase then catalyzes elongation of
glycogen chains initiated by Glycogenin.
Question: Where would you expect to find
Glycogenin within a cell?
20. Glycogen Synthase catalyzes transfer of the glucose
moiety of UDP-glucose to the hydroxyl at C4 of the
terminal residue of a glycogen chain to form an
α(1→ 4) glycosidic linkage:
glycogen(nresidues)
+ UDP-glucose
glycogen(n+1residues)
+ UDP
A branching enzyme transfers a segment from the end of
a glycogen chain to the C6 hydroxyl of a glucose residue
of glycogen to yield a branch with an α(1→6) linkage.
21. Both synthesis & breakdown of glycogen are spontaneous.
If both pathways were active simultaneously in a cell,
there would be a "futile cycle" with cleavage of one ~P
bond per cycle (in forming UDP-glucose).
To prevent such a futile cycle, Glycogen Synthase and
Glycogen Phosphorylase are reciprocally regulated, by
allosteric effectors and by phosphorylation.
Glycogen Synthesis
UTP UDP + 2 Pi
glycogen(n) + glucose-1-P glycogen(n + 1)
Glycogen Phosphorylase Pi
22. Glycogen Phosphorylase in muscle is subject to allosteric
regulation by AMP, ATP, and glucose-6-phosphate.
A separate isozyme of Phosphorylase expressed in liver is
less sensitive to these allosteric controls.
AMP (present significantly when ATP is depleted)
activates Phosphorylase, promoting the relaxed
conformation.
ATP & glucose-6-phosphate, which both have binding
sites that overlap that of AMP, inhibit Phosphorylase,
promoting the tense conformation.
Thus glycogen breakdown is inhibited when ATP and
glucose-6-phosphate are plentiful.
23. Glycogen Synthase is allosterically activated by
glucose-6-P (opposite of effect on Phosphorylase).
Thus Glycogen Synthase is active when high blood
glucose leads to elevated intracellular glucose-6-P.
It is useful to a cell to store glucose as glycogen when the
input to Glycolysis (glucose-6-P), and the main product
of Glycolysis (ATP), are adequate.
Glycogen Glucose
Hexokinase or Glucokinase
Glucose-6-Pase
Glucose-1-P Glucose-6-P Glucose + Pi
Glycolysis
Pathway
Pyruvate
Glucose metabolism in liver.
24. Regulation by covalent modification
(phosphorylation):
The hormones glucagon and epinephrine activate
G-protein coupled receptors to trigger cAMP cascades.
Both hormones are produced in response to low
blood sugar.
Glucagon, which is synthesized by α-cells of the
pancreas, activates cAMP formation in liver.
Epinephrine activates cAMP formation in muscle.
25. The cAMP cascade results in phosphorylation of a serine
hydroxyl of Glycogen Phosphorylase, which promotes
transition to the active (relaxed) state.
The phosphorylated enzyme is less sensitive to allosteric
inhibitors.
Thus, even if cellular ATP & glucose-6-phosphate are
high, Phosphorylase will be active.
The glucose-1-phosphate produced from glycogen in liver
may be converted to free glucose for release to the blood.
With this hormone-activated regulation, the needs of the
organism take precedence over needs of the cell.
26. Commonly used terminology:
"a" is the form of the enzyme that tends to be active,
and independent of allosteric regulators (in the case of
Glycogen Phosphorylase, when phosphorylated).
"b" is the form of the enzyme that is dependent on
local allosteric controls (in the case of Glycogen
Phosphorylase when dephosphorylated).
27. Signal
cascade by
which
Glycogen
Phosphorylase
is activated.
Hormone (epinephrine or glucagon)
via G Protein (Gα-GTP)
Adenylate cyclase Adenylate cyclase
(inactive) (active)
catalysis
ATP cyclic AMP + PPi
Activation Phosphodiesterase
AMP
Protein kinase A Protein kinase A
(inactive) (active)
ATP
ADP
Phosphorylase kinase Phosphorylase kinase (P)
(b-inactive) (a-active)
Phosphatase ATP
Pi ADP
Phosphorylase Phosphorylase (P)
(b-allosteric) (a-active)
Phosphatase
Pi
28. The cAMP cascade induced in liver by glucagon or
epinephrine has the opposite effect on glycogen
synthesis.
Glycogen Synthase is phosphorylated by Protein
Kinase A as well as by Phosphorylase Kinase.
Phosphorylation of Glycogen Synthase promotes the
"b" (less active) conformation.
The cAMP cascade thus inhibits glycogen synthesis.
Instead of being converted to glycogen, glucose-1-P
in liver may be converted to glucose-6-P, and
dephosphorylated for release to the blood.
29. High cytosolic glucose-6-phosphate, which would result
when blood glucose is high, turns off the signal with
regard to glycogen synthesis.
The conformation of Glycogen Synthase induced by the
allosteric activator glucose-6-phosphate is susceptible to
dephosphorylation by Protein Phosphatase.
Glycogen Glucose
Hexokinase or Glucokinase
Glucose-6-Pase
Glucose-1-P Glucose-6-P Glucose + Pi
Glycolysis
Pathway
Pyruvate
Glucose metabolism in liver.
30. Insulin, produced in response to high blood glucose,
triggers a separate signal cascade that leads to
activation of Phosphoprotein Phosphatase.
This phosphatase catalyzes removal of regulatory
phosphate residues from Phosphorylase, Phosphorylase
Kinase, & Glycogen Synthase enzymes.
Thus insulin antagonizes effects of the cAMP cascade
induced by glucagon & epinephrine.
31. Ca++
also regulates glycogen breakdown in muscle.
During activation of contraction in skeletal muscle, Ca++
is
released from the sarcoplasmic reticulum to promote
actin/myosin interactions.
The released Ca++
also activates Phosphorylase Kinase,
which in muscle includes calmodulin as its δ subunit.
Phosphorylase Kinase is partly activated by binding of
Ca++
to this subunit.
Phosphorylase Kinase inactive
Phosphorylase Kinase-Ca++
partly active
P-Phosphorylase Kinase-Ca++
fully active
32. Phosphorylation of the enzyme, via a cAMP cascade
induced by epinephrine, results in further activation.
These regulatory processes ensure release of phosphorylated
glucose from glycogen, for entry into Glycolysis to provide
ATP needed for muscle contraction.
During extended exercise, as glycogen stores become
depleted, muscle cells rely more on glucose uptake from
the blood, and on fatty acid catabolism as a source of ATP.
Phosphorylase Kinase inactive
Phosphorylase Kinase-Ca++
partly active
P-Phosphorylase Kinase-Ca++
fully active
33. A genetic defect in the isoform of an enzyme expressed in
liver causes the following symptoms:
After eating a CHO meal, elevated blood levels of
glucose, lactate, & lipids.
During fasting, low blood glucose & high ketone bodies.
Which liver enzyme is defective?
Explain Symptoms:
After eating, blood glucose is high because liver cannot
store it as glycogen. Some excess glucose is processed
via Glycolysis to produce lactate & fatty acid precursors.
During fasting, glucose is low because the liver lacks
glycogen stores for generation of glucose.
Ketone bodies are produced as an alternative fuel.
Glycogen Synthase
34. Question: How would you nutritionally treat
deficiency of liver Glycogen Synthase?
Frequent meals of complex carbohydrates
(avoiding simple sugars that would lead to a rapid
rise in blood glucose)
Meals high in protein to provide substrates for
gluconeogenesis.
35. Glycogen Storage
Diseases are genetic
enzyme deficiencies
associated with excessive
glycogen accumulation
within cells.
Some enzymes whose
deficiency leads to
glycogen accumulation
are part of the inter-
connected pathways
shown here.
glycogen
glucose-1-P
Glucose-6-Phosphatase
glucose-6-P glucose + Pi
fructose-6-P
Phosphofructokinase
fructose-1,6-bisP
Glycolysis continued
36. Symptoms in addition to excess glycogen storage:
When a genetic defect affects mainly an isoform of an
enzyme expressed in liver, a common symptom is
hypoglycemia, relating to impaired mobilization of
glucose for release to the blood during fasting.
When the defect is in muscle tissue, weakness &
difficulty with exercise result from inability to
increase glucose entry into Glycolysis during exercise.
Additional symptoms depend on the particular
enzyme that is deficient.
37. Glycogen Storage Disease
Symptoms, in addition to
glycogen accumulation
Type I, liver deficiency of
Glucose-6-phosphatase (von
Gierke's disease)
hypoglycemia (low blood
glucose) when fasting, liver
enlargement.
Type IV, deficiency of
branching enzyme in various
organs, including liver
(Andersen's disease)
liver dysfunction and early
death.
Type V, muscle deficiency of
Glycogen Phosphorylase
(McArdle's disease)
muscle cramps with exercise.
Type VII, muscle deficiency of
Phosphofructokinase.
inability to exercise.