Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt

  >   Rahul's Noteblog   >   Notes on Biochemistry   >   Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt

Glycogen synthesis:

• Synthesis begins with glycogenin, which isconverted to glucose 1-phosphate and activated by UDP-glucose.

• Glycogen synthase is the rate limiting enzyme; forms alpha 1, 4 glycosidic bonds.

• Activated by insulin and glucose in liver; inhibited by glucagon and epinephrine in liver.

• Activated by insulin in skeletal muscle; inhibited by epinephrine in skeletal muscle.

Glycogenolysis:

• Rate limiting enzyme is: glycogen phosphorylase.

• Breaks alpha 1, 4 glycosidic bonds, releasing glucose 1-phosphate.

• Activated by epinephrine and glucagon in liver; inhibited by insulin in liver.

• Activated by epinephrine, AMP and Ca2+ in skeletal muscle; inhibited by insulin and ATP in skeletal muscle.

Glycogen Storage Disease:

von Gierke's Disease:

• Deficiency of glucose-6-phosphatase.

Pompe's Disease:

• Deficiency of lysosomal alpha 1,4-glucosidase.

Cori's Disease:

• Deficiency of glycogen debranching enzyme.

Andersen (amylopectinosis):

• Deficiency of debranching enzyme.

McArdle's Disease:

• Dficiency of muscle glycogen phosphorylase.

Hers:

• Deficiency of hepatic glycogen phosphorylase.

Functions of Debranching Enzyme:

• Deconstructs branches of glycogen that have been exposed by glycogen phosphorylase.

• Breaks alpha 1,4 glycosidic and alpha 1,6 glycosidic bonds, and forms a new alpha 1,4 glycosidic bond.

Functions of Branching Enzyme:

• Constructs branches of glycogen that have been exposed to glycogen synthase.

• Breaks alpha 1,4 glycosidic bond and forms a new alpha 1,4 glycosidic bond.

Von Gierke's Disease:

• Deficiency of glucose-6-phosphatase.

• Fasting hypoglycemia, lactic acidosis, hepatomegaly.

• Glycogen deposits in liver; fatty liver; hyperuricemia, hyperlipidemia.

• Ingestion of galactose or fructose causes no increase in blood glucose.

• Hyperuricemia, hyperlipidemia, elevated VLDLs.

McArdle's Disease:

• Deficiency of muscle glycogen physphorylase.

• Exercise intolerance.

• Muscles lack glucose.

• Muscle cramping, myoglobinuria.

Pompe's Disease:

• Deficiency of lysosomal alpha 1,4-glucosidase.

• Glycogen-like material acclimates in endosomes.

• Massive cardiomegaly.

• Muscle degeneration, enlarged liver, difficulty breathing.

• Use enzyme replacement therapy.

Cori's Disease:

• Deficiency of glycogen debranching enzyme.

• Mild hypoglycemia, liver enlargement.

Gluconeogenesis:

• Occurs in liver.

• Promoted by glucagon and epinephrine.

• Inhibited by insulin.

• Fructose and galactose can also be converted to glucose in liver.

Pyruvate carboxylase:

• Located in mitochondria; requires biotin; activated by acetyl-CoA.

Phosphoenolpyruvate carboxykinase: (PEPCK):

• Located in cytoplasm; converts OAA to PEP in cytoplasm; induced by glycogen and cortisol.

Fructose-1,6-bisphosphate:

• Located in cytoplasm; activated by ATP; inhibited by AMP and fructose 2,6-bisphosphate.

Glucose-6-phosphatase:

• Located in ER; lies in ER or liver cells.

Acetyl-CoA from fatty acids cannot be converted to glucose, but it can be converted to ketones.

Cori cycle and Alanine cycle:

• During fasting, lactate from RBCs in converted to glucose in liver and returned to RBC.

Alcoholism and Hypoglycemia:

• Alcohol metabolized to acetyl-CoA.

• NADH produced during alcohol metabolism interferes with gluconeogenesis.

• NADH causes production of: lactate, malate, and glycerol 3-phosphate.

Thus, glycerol 3-phosphate causes lipid accumulation in liver alcoholic disease. Alcohol consumption after work-outs causes hypoglycemia. NAD, required for lactate metabolism (and lactate is used for gluconeogenesis), is being used for alcohol metabolism.

HMP shunt:

• Occurs in the cytoplasm of all cells.

• NADPH production and ribose 5-phosphate for nucleotide synthesis.

• NADPH uses: biosynthesis, protection against reactive oxygen species, and bactericidial activity in PMNs.

G6PDH deficiency:

• Hemolytic anemia.

• XR inheritance.

• RBCs generate ROSs that damage protein and lipid in cell.

• RBCs themselves are protected by presence of glutathione peroxidase / glutathione reductase system.

• In presence of ROSs, hemoglobin precipitate (Heinz bodies) causing hemolysis.

• Hemolysis is accelerated in persons with G6PDH deficiency.

Additional Notes:

• During starvation, acetyl CoA activates: pyruvate carboxylase.

• Glucose-6-phosphatase: necessary for glucose to leave the cell.

• Decreased insulin: mobilizes amino acidsfrom muscle proteins, stimulating gluconeogenesis.

• RBCs use glucose and generate lactate; lactate + alanine is then taken up by livers cells, converted to glucose by rate-limiting reagent PEP carboxykinase, and the glucose is then sent back to RBCs.

• Pyruvate carboxylase regulated by acetyl CoA.

• Pyruvate converted to oxaloacetate: mitochondria.

• Coenzyme of pyruvate carboxylase: biotin.

• Ethanol decreases the rate of gluconeogenesis: decreased availability of pyruvate.

• Muscle doesn't have glucose-6-phosphatase.

Additional Readings:

Basic Biochemistry

1. Nucleic Acid Structure and Organization
2. DNA Replication and Repair
3. Transcription and RNA Processing
4. Genetic Code, Mutations, and Translation
5. Genetic Regulation
6. Recombinant DNA
7. Amino Acids, Proteins, Enzymes
8. Hormones
9. Vitamins
10. Energy Metabolism
11. Glycolysis and Pyruvate Dehydrogenase
12. Citric Acid Cycle and Oxidative Phosphorylation
13. Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt
14. Lipid Synthesis and Storage
15. Lipid Mobilization and Catabolism
16. Amino Acid Metabolism Disorders
17. Purine and Pyrimidine Metabolism
18. Electron Transport
19. Citric Acid Cycle and Glyoxylate Cycle
20. Glycolysis
21. Pyruvate Metabolism
22. Mitochondrial ATP formation
23. Gluconeogenesis
24. Glycogen Metabolism
25. Nitrogen Fixation (Metabolism) reactions, and Heme Metabolism
26. Amino Acid Metabolism
27. What is Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)?

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