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823984 gluconeo-glycogen-metabolism

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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.

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GLYCOGEN METABOLISM GLUCONEOGENESIS
GLUCONEOGENESIS synthesis of glucose from noncarbohydrate precursors during longer periods of starvation a very important pathway since the brain depends on glucose as its primary fuel ( 120g of the 160g daily need for glucose ) and RBCs use only glucose as fuel amount of glucose in body fluids is 20g and the amount that can be derived from glycogen is 190g major noncarbohydrate sources are lactate , amino acids , and glycerol
noncarbohydrate sources need to be first converted to either pyruvate , oxaloacetate or dihydroxyacetone phosphate (DHAP) to be converted to glucose major site is the liver with small amount taking place in the kidneys gluconeogenesis in the liver and kidneys helps maintain the glucose demands of the brain and muscles by increasing blood glucose levels little occurs in the brain, skeletal muscle or heart muscle not a reversal of glycolysis
NONCARBOHYDRATE SOURCES Pyruvate is converted to glucose in the gluconeogenetic pathway Lactate is formed by active skeletal muscle when glycolytic rate exceeds oxidative rate; becomes glucose by first converting it to pyruvate Amino acids are derived from dietary proteins and internal protein breakdown during starvation ; becomes glucose by converting them first to either pyruvate or oxaloacetate Glycerol is derived from the hydrolysis of triacylglycerols (TAG) or triglycerides ; becomes glucose by conversion first to dihydroxyacetone phosphate (DHAP)
IRREVERSIBLE STEPS of GLYCOLYSIS Causes of most of the decrease in free energy in glycolysis Bypassed steps during gluconeogenesis Steps catalyzed by the enzymes Hexokinase ( glucose + ATP  G-6-P + ADP ) Phosphofructokinase ( F-6-P + ATP  F-1,6-BP + ADP ) Pyruvate kinase ( PEP + ADP  Pyruvate + ATP )
NEW STEPS in GLUCOSE FORMATION from PYRUVATE via GLUCONEOGENESIS PEP is formed from pyruvate by way of oxaloacetate Pyruvate + CO 2 + ATP + HOH ------------  oxaloacetate + ADP + Pi + 2H + Oxaloacetate + GTP -------------  PEP + GDP + CO 2 F-6-P is formed from F-1,6-BP by hydrolysis of the phosphate ester at carbon 1, an exergonic hydrolysis Fructose-1,6-bisphosphate + HOH --------------  fructose-6-phosphate + Pi Glucose is formed by hydrolysis of G-6-P Glucose-6-phosphate + HOH -------------  glucose + Pi Pyruvate carboxylase PEP carboxykinase Fructose-1,6-bisphosphatase Glucose-6-phosphatase
RECIPROCAL REGULATION OF GLYCOLYSIS & GLUCONEOGENESIS Glucose Fructose-6-phosphate Fructose-1,6-bisphosphate PEP Pyruvate Oxaloacetate PFK F-1,6-BPase Several steps PK PEP carboxykinase Pyruvate carboxylase GLUCONEOGENESIS F-2,6-BP + AMP + ATP - Citrate - H + - F-2,6-BP - AMP - Citrate + F-1,6-BP + ATP - Alanine - AcetylCoA + ADP - ADP -
GLYCOGEN Readily mobilized storage form of glucose very large, branched polymer of glucose residues linked via α -1,4 (straight) and α - 1,6 glycosidic bonds branching occurs for every 10 th glucose residue of the open helical polymer not as reduced as fatty acids are and consequently not as energy-rich serves as buffer to maintain blood sugar levels Released glucose from glycogen can provide energy anaerobically unlike fatty acids
Two major sites of glycogen storage are the liver (10% by weight) and skeletal muscles (2% by weight) In the liver, its synthesis and degradation are regulated to maintain normal blood glucose in the muscles, its synthesis and degradation is intended to meet the energy needs of the muscle itself present in the cytosol as granules (10-40nm)
GLYCOGENOLYSIS Consists of three steps 1. release of glucose-1-phosphate from from the nonreducing ends of glycogen (phosphorolysis) 2. remodeling of glycogen substrate to permit further degradation with a transferase and α -1,6 glucosidase 3. conversion of glucose-1-phosphate to glucose-6-phosphate for further metabolism
Fates of Glucose-6-Phosphate Initial substrate for glycolysis Can be processed by the pentose phosphate pathway to NADPH and ribose derivatives Can be converted to free glucose in the liver, intestine and kidneys for release into the blood stream
Glycogen Glycogen n-1 Glucose-1-phosphate Glucose-6-phosphate Glycolysis PPP Pyruvate Glucose Ribose + NADPH Lactate CO 2 + HOH Blood for use by other tissues Muscle,Brain Liver Glycogen phosphorylase Glucose-6-phosphatase Phosphoglucomutase
GLYCOGENESIS Regulated by a complex system and requires a primer, glycogenin Requires an activated form of glucose , the Uridine diphosphate glucose (UDP- glucose) formed from UTP and glucose-1- phosphate UDP-glucose is added to the nonreducing end of glycogen using glycogen synthase , the key regulatory enzyme in glycogen synthesis Glycogen is then remodeled for continued synthesis
GLYCOGEN BREAKDOWN & SYNTHESIS ARE RECIPROCALLY REGULATED Glycogen breakdown Glycogen synthesis Epinephrine Adenylate cyclase Adenylate cyclase ATP cAMP Protein kinase A Protein kinase A Phosphorylase kinase Phosphorylase kinase Phosphorylase b Phosphorylase a Glycogen synthase a Glycogen synthase b PINK – inactive GREEN - active
GLYCOGEN STORAGE DISEASE TYPE DEFECTIVE ENZYME ORGAN AFFECTED GLYCOGEN IN AFFECTED ORGAN CLINICAL FEATURES I (Von Gierke) Glucose-6-phosphatase Liver & kidney Increased amount; normal structure Hepatomegaly, failure to thrive, hypoglycemia, ketosis, hyperuricemia, hyperlipidemia II (Pompe dse) α -1,4 glucosidase All organs Massive increase in amount; normal structure Cardiorespiratory failure causes death usually before age 2 III (Cori dse) Amylo-1,6-glucosidase (debranching) Muscle & liver Increased amount; short outer branches Like type 1 but milder IV (Andersen dse) Branching enzyme ( α -1,4 & 1,6) Liver & spleen Normal amount; very long outer branches Progressive cirrhosis of the liver; liver failure causes death before age 2 V (McArdle dse) Phosphorylase muscle Moderately increased amount; normal structure Limited ability to perform strenuous exercise because of painful muscle cramps. Otherwise patient is normal or well-developed. VI (Hers dse) Phosphorylase liver Increased amount Like type 1 but milder VII Phosphofructokinase muscle Increased amount; normal structure Like type V VIII Phosphorylase kinase liver Increased amount; normal structure Mild liver enlargement. Mild hypoglycemia
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823984 gluconeo-glycogen-metabolism

  • 1. www.Examville.com Online practice tests, live classes, tutoring, study guides Q&A, premium content and more .
  • 3. GLUCONEOGENESIS synthesis of glucose from noncarbohydrate precursors during longer periods of starvation a very important pathway since the brain depends on glucose as its primary fuel ( 120g of the 160g daily need for glucose ) and RBCs use only glucose as fuel amount of glucose in body fluids is 20g and the amount that can be derived from glycogen is 190g major noncarbohydrate sources are lactate , amino acids , and glycerol
  • 4. noncarbohydrate sources need to be first converted to either pyruvate , oxaloacetate or dihydroxyacetone phosphate (DHAP) to be converted to glucose major site is the liver with small amount taking place in the kidneys gluconeogenesis in the liver and kidneys helps maintain the glucose demands of the brain and muscles by increasing blood glucose levels little occurs in the brain, skeletal muscle or heart muscle not a reversal of glycolysis
  • 5. NONCARBOHYDRATE SOURCES Pyruvate is converted to glucose in the gluconeogenetic pathway Lactate is formed by active skeletal muscle when glycolytic rate exceeds oxidative rate; becomes glucose by first converting it to pyruvate Amino acids are derived from dietary proteins and internal protein breakdown during starvation ; becomes glucose by converting them first to either pyruvate or oxaloacetate Glycerol is derived from the hydrolysis of triacylglycerols (TAG) or triglycerides ; becomes glucose by conversion first to dihydroxyacetone phosphate (DHAP)
  • 6. IRREVERSIBLE STEPS of GLYCOLYSIS Causes of most of the decrease in free energy in glycolysis Bypassed steps during gluconeogenesis Steps catalyzed by the enzymes Hexokinase ( glucose + ATP  G-6-P + ADP ) Phosphofructokinase ( F-6-P + ATP  F-1,6-BP + ADP ) Pyruvate kinase ( PEP + ADP  Pyruvate + ATP )
  • 7. NEW STEPS in GLUCOSE FORMATION from PYRUVATE via GLUCONEOGENESIS PEP is formed from pyruvate by way of oxaloacetate Pyruvate + CO 2 + ATP + HOH ------------  oxaloacetate + ADP + Pi + 2H + Oxaloacetate + GTP -------------  PEP + GDP + CO 2 F-6-P is formed from F-1,6-BP by hydrolysis of the phosphate ester at carbon 1, an exergonic hydrolysis Fructose-1,6-bisphosphate + HOH --------------  fructose-6-phosphate + Pi Glucose is formed by hydrolysis of G-6-P Glucose-6-phosphate + HOH -------------  glucose + Pi Pyruvate carboxylase PEP carboxykinase Fructose-1,6-bisphosphatase Glucose-6-phosphatase
  • 8. RECIPROCAL REGULATION OF GLYCOLYSIS & GLUCONEOGENESIS Glucose Fructose-6-phosphate Fructose-1,6-bisphosphate PEP Pyruvate Oxaloacetate PFK F-1,6-BPase Several steps PK PEP carboxykinase Pyruvate carboxylase GLUCONEOGENESIS F-2,6-BP + AMP + ATP - Citrate - H + - F-2,6-BP - AMP - Citrate + F-1,6-BP + ATP - Alanine - AcetylCoA + ADP - ADP -
  • 9. GLYCOGEN Readily mobilized storage form of glucose very large, branched polymer of glucose residues linked via α -1,4 (straight) and α - 1,6 glycosidic bonds branching occurs for every 10 th glucose residue of the open helical polymer not as reduced as fatty acids are and consequently not as energy-rich serves as buffer to maintain blood sugar levels Released glucose from glycogen can provide energy anaerobically unlike fatty acids
  • 10. Two major sites of glycogen storage are the liver (10% by weight) and skeletal muscles (2% by weight) In the liver, its synthesis and degradation are regulated to maintain normal blood glucose in the muscles, its synthesis and degradation is intended to meet the energy needs of the muscle itself present in the cytosol as granules (10-40nm)
  • 11. GLYCOGENOLYSIS Consists of three steps 1. release of glucose-1-phosphate from from the nonreducing ends of glycogen (phosphorolysis) 2. remodeling of glycogen substrate to permit further degradation with a transferase and α -1,6 glucosidase 3. conversion of glucose-1-phosphate to glucose-6-phosphate for further metabolism
  • 12. Fates of Glucose-6-Phosphate Initial substrate for glycolysis Can be processed by the pentose phosphate pathway to NADPH and ribose derivatives Can be converted to free glucose in the liver, intestine and kidneys for release into the blood stream
  • 13. Glycogen Glycogen n-1 Glucose-1-phosphate Glucose-6-phosphate Glycolysis PPP Pyruvate Glucose Ribose + NADPH Lactate CO 2 + HOH Blood for use by other tissues Muscle,Brain Liver Glycogen phosphorylase Glucose-6-phosphatase Phosphoglucomutase
  • 14. GLYCOGENESIS Regulated by a complex system and requires a primer, glycogenin Requires an activated form of glucose , the Uridine diphosphate glucose (UDP- glucose) formed from UTP and glucose-1- phosphate UDP-glucose is added to the nonreducing end of glycogen using glycogen synthase , the key regulatory enzyme in glycogen synthesis Glycogen is then remodeled for continued synthesis
  • 15. GLYCOGEN BREAKDOWN & SYNTHESIS ARE RECIPROCALLY REGULATED Glycogen breakdown Glycogen synthesis Epinephrine Adenylate cyclase Adenylate cyclase ATP cAMP Protein kinase A Protein kinase A Phosphorylase kinase Phosphorylase kinase Phosphorylase b Phosphorylase a Glycogen synthase a Glycogen synthase b PINK – inactive GREEN - active
  • 16. GLYCOGEN STORAGE DISEASE TYPE DEFECTIVE ENZYME ORGAN AFFECTED GLYCOGEN IN AFFECTED ORGAN CLINICAL FEATURES I (Von Gierke) Glucose-6-phosphatase Liver & kidney Increased amount; normal structure Hepatomegaly, failure to thrive, hypoglycemia, ketosis, hyperuricemia, hyperlipidemia II (Pompe dse) α -1,4 glucosidase All organs Massive increase in amount; normal structure Cardiorespiratory failure causes death usually before age 2 III (Cori dse) Amylo-1,6-glucosidase (debranching) Muscle & liver Increased amount; short outer branches Like type 1 but milder IV (Andersen dse) Branching enzyme ( α -1,4 & 1,6) Liver & spleen Normal amount; very long outer branches Progressive cirrhosis of the liver; liver failure causes death before age 2 V (McArdle dse) Phosphorylase muscle Moderately increased amount; normal structure Limited ability to perform strenuous exercise because of painful muscle cramps. Otherwise patient is normal or well-developed. VI (Hers dse) Phosphorylase liver Increased amount Like type 1 but milder VII Phosphofructokinase muscle Increased amount; normal structure Like type V VIII Phosphorylase kinase liver Increased amount; normal structure Mild liver enlargement. Mild hypoglycemia
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