823984 gluconeo-glycogen-metabolism
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823984 gluconeo-glycogen-metabolism

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823984 gluconeo-glycogen-metabolism 823984 gluconeo-glycogen-metabolism Presentation Transcript

  • www.Examville.com Online practice tests, live classes, tutoring, study guides Q&A, premium content and more .
    • 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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