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<ul><li>GLYCOGEN METABOLISM </li></ul>GLUCONEOGENESIS
GLUCONEOGENESIS <ul><li>synthesis of glucose from noncarbohydrate  precursors during longer periods of  starvation </li></...
<ul><li>noncarbohydrate sources need to be first  converted to either  </li></ul><ul><li>pyruvate , </li></ul><ul><li>oxal...
NONCARBOHYDRATE SOURCES <ul><li>Pyruvate  is converted to glucose in the gluconeogenetic pathway </li></ul><ul><li>Lactate...
IRREVERSIBLE STEPS of GLYCOLYSIS <ul><li>Causes of most of the decrease in free energy  in glycolysis </li></ul><ul><li>By...
NEW STEPS in GLUCOSE FORMATION from PYRUVATE via GLUCONEOGENESIS <ul><li>PEP is formed from pyruvate by way of  oxaloaceta...
RECIPROCAL REGULATION OF GLYCOLYSIS & GLUCONEOGENESIS Glucose Fructose-6-phosphate Fructose-1,6-bisphosphate PEP Pyruvate ...
GLYCOGEN  <ul><li>Readily mobilized storage form of glucose </li></ul><ul><li>very large, branched polymer of glucose  res...
<ul><li>Two major sites of glycogen storage are the liver (10% by weight) and skeletal muscles (2% by weight) </li></ul><u...
GLYCOGENOLYSIS <ul><li>Consists of three steps </li></ul><ul><li>1.  release of glucose-1-phosphate from  from the nonredu...
Fates of Glucose-6-Phosphate <ul><li>Initial substrate for  glycolysis </li></ul><ul><li>Can be processed by the  pentose ...
<ul><li>Glycogen </li></ul><ul><li>Glycogen  n-1 </li></ul><ul><li>Glucose-1-phosphate </li></ul><ul><li>Glucose-6-phospha...
GLYCOGENESIS <ul><li>Regulated by a complex system and requires a primer,  glycogenin </li></ul><ul><li>Requires an  activ...
GLYCOGEN BREAKDOWN & SYNTHESIS ARE RECIPROCALLY REGULATED <ul><li>Glycogen breakdown   Glycogen synthesis </li></ul>Epinep...
GLYCOGEN STORAGE DISEASE TYPE DEFECTIVE ENZYME ORGAN AFFECTED GLYCOGEN IN AFFECTED ORGAN CLINICAL FEATURES I (Von Gierke) ...
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823984 gluconeo-glycogen-metabolism

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823984 gluconeo-glycogen-metabolism

  1. 1. www.Examville.com Online practice tests, live classes, tutoring, study guides Q&A, premium content and more .
  2. 2. <ul><li>GLYCOGEN METABOLISM </li></ul>GLUCONEOGENESIS
  3. 3. GLUCONEOGENESIS <ul><li>synthesis of glucose from noncarbohydrate precursors during longer periods of starvation </li></ul><ul><li>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 </li></ul><ul><li>amount of glucose in body fluids is 20g and the amount that can be derived from glycogen is 190g </li></ul><ul><li>major noncarbohydrate sources are lactate , amino acids , and glycerol </li></ul>
  4. 4. <ul><li>noncarbohydrate sources need to be first converted to either </li></ul><ul><li>pyruvate , </li></ul><ul><li>oxaloacetate or </li></ul><ul><li>dihydroxyacetone phosphate (DHAP) </li></ul><ul><li>to be converted to glucose </li></ul><ul><li>major site is the liver with small amount taking place in the kidneys </li></ul><ul><li>gluconeogenesis in the liver and kidneys helps maintain the glucose demands of the brain and muscles by increasing blood glucose levels </li></ul><ul><li>little occurs in the brain, skeletal muscle or heart muscle </li></ul><ul><li>not a reversal of glycolysis </li></ul>
  5. 5. NONCARBOHYDRATE SOURCES <ul><li>Pyruvate is converted to glucose in the gluconeogenetic pathway </li></ul><ul><li>Lactate is formed by active skeletal muscle when glycolytic rate exceeds oxidative rate; becomes glucose by first converting it to pyruvate </li></ul><ul><li>Amino acids are derived from dietary proteins and internal protein breakdown during starvation ; becomes glucose by converting them first to either pyruvate or oxaloacetate </li></ul><ul><li>Glycerol is derived from the hydrolysis of triacylglycerols (TAG) or triglycerides ; becomes glucose by conversion first to dihydroxyacetone phosphate (DHAP) </li></ul>
  6. 6. IRREVERSIBLE STEPS of GLYCOLYSIS <ul><li>Causes of most of the decrease in free energy in glycolysis </li></ul><ul><li>Bypassed steps during gluconeogenesis </li></ul><ul><li>Steps catalyzed by the enzymes </li></ul><ul><ul><li>Hexokinase </li></ul></ul><ul><ul><li>( glucose + ATP  G-6-P + ADP ) </li></ul></ul><ul><ul><li>Phosphofructokinase </li></ul></ul><ul><ul><li>( F-6-P + ATP  F-1,6-BP + ADP ) </li></ul></ul><ul><ul><li>Pyruvate kinase </li></ul></ul><ul><ul><li>( PEP + ADP  Pyruvate + ATP ) </li></ul></ul>
  7. 7. NEW STEPS in GLUCOSE FORMATION from PYRUVATE via GLUCONEOGENESIS <ul><li>PEP is formed from pyruvate by way of oxaloacetate </li></ul><ul><ul><ul><li>Pyruvate + CO 2 + ATP + HOH ------------  oxaloacetate + ADP + Pi + 2H + </li></ul></ul></ul><ul><ul><ul><li>Oxaloacetate + GTP -------------  PEP + GDP + CO 2 </li></ul></ul></ul><ul><li>F-6-P is formed from F-1,6-BP by hydrolysis of the phosphate ester at carbon 1, an exergonic hydrolysis </li></ul><ul><ul><ul><li>Fructose-1,6-bisphosphate + HOH --------------  fructose-6-phosphate + Pi </li></ul></ul></ul><ul><li>Glucose is formed by hydrolysis of G-6-P </li></ul><ul><ul><ul><li>Glucose-6-phosphate + HOH -------------  glucose + Pi </li></ul></ul></ul>Pyruvate carboxylase PEP carboxykinase Fructose-1,6-bisphosphatase Glucose-6-phosphatase
  8. 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. 9. GLYCOGEN <ul><li>Readily mobilized storage form of glucose </li></ul><ul><li>very large, branched polymer of glucose residues linked via α -1,4 (straight) and α - 1,6 glycosidic bonds </li></ul><ul><li>branching occurs for every 10 th glucose residue of the open helical polymer </li></ul><ul><li>not as reduced as fatty acids are and consequently not as energy-rich </li></ul><ul><li>serves as buffer to maintain blood sugar levels </li></ul><ul><li>Released glucose from glycogen can provide energy anaerobically unlike fatty acids </li></ul>
  10. 10. <ul><li>Two major sites of glycogen storage are the liver (10% by weight) and skeletal muscles (2% by weight) </li></ul><ul><li>In the liver, its synthesis and degradation are regulated to maintain normal blood glucose </li></ul><ul><li>in the muscles, its synthesis and degradation is intended to meet the energy needs of the muscle itself </li></ul><ul><li>present in the cytosol as granules (10-40nm) </li></ul>
  11. 11. GLYCOGENOLYSIS <ul><li>Consists of three steps </li></ul><ul><li>1. release of glucose-1-phosphate from from the nonreducing ends of glycogen (phosphorolysis) </li></ul><ul><li>2. remodeling of glycogen substrate to permit further degradation with a transferase and α -1,6 glucosidase </li></ul><ul><li>3. conversion of glucose-1-phosphate to glucose-6-phosphate for further metabolism </li></ul>
  12. 12. Fates of Glucose-6-Phosphate <ul><li>Initial substrate for glycolysis </li></ul><ul><li>Can be processed by the pentose phosphate pathway to NADPH and ribose derivatives </li></ul><ul><li>Can be converted to free glucose in the liver, intestine and kidneys for release into the blood stream </li></ul>
  13. 13. <ul><li>Glycogen </li></ul><ul><li>Glycogen n-1 </li></ul><ul><li>Glucose-1-phosphate </li></ul><ul><li>Glucose-6-phosphate </li></ul><ul><li>Glycolysis PPP </li></ul><ul><li>Pyruvate Glucose Ribose + </li></ul><ul><li> NADPH </li></ul><ul><li>Lactate CO 2 + HOH </li></ul><ul><li> Blood for use by </li></ul><ul><li> other tissues </li></ul>Muscle,Brain Liver Glycogen phosphorylase Glucose-6-phosphatase Phosphoglucomutase
  14. 14. GLYCOGENESIS <ul><li>Regulated by a complex system and requires a primer, glycogenin </li></ul><ul><li>Requires an activated form of glucose , the </li></ul><ul><li>Uridine diphosphate glucose (UDP- glucose) formed from UTP and glucose-1- phosphate </li></ul><ul><li>UDP-glucose is added to the nonreducing end of glycogen using glycogen synthase , the key regulatory enzyme in glycogen synthesis </li></ul><ul><li>Glycogen is then remodeled for continued synthesis </li></ul>
  15. 15. GLYCOGEN BREAKDOWN & SYNTHESIS ARE RECIPROCALLY REGULATED <ul><li>Glycogen breakdown Glycogen synthesis </li></ul>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. 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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