Download NME2.28: fat and carbohydrate metabolism in the

NME2.28: FAT AND CARBOHYDRATE METABOLISM IN THE ABSORPTIVE STATE
05/03/08
GLYCOGEN SYNTHESIS AND DEGRADATION
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Glycogen is a branched glucose storage polymer consisting of α1-4 and α1-6 bonds
o These branched bonds allow rapid degradation to generate glucose
Synthesis of glycogen is catalysed by de-phosphorylated glycogen synthase (GS)
o Synthase phosphatase (SP) activates GS
o Synthase kinase (SK) deactivates GS
Degradation of glycogen is catalysed by phosphorylated glycogen phosphorylase (GP)
o Phosphorylase kinase (PK) activates GP
o Phosphorylase phosphatase (PP) deactivates GP
Hormonal control of glycogen synthesis and degradation is through:
o Insulin – stimulates the phosphatases promoting glycogen synthesis
o Glucagon – stimulates the kinases promoting glycogen degradation
Non-hormonal control of glycogen synthesis and degradation is through:
o Glucose-6P stimulates SP and glucose stimulates PP promoting glycogen synthesis
o Adrenaline stimulates the kinases promoting glycogen degradation
FATTY ACID SYNTHESIS
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The liver has a limited glycogen storage capacity (approximately 100g)
Excess glucose and amino acids are converted to fatty acids and ultimately triglycerides to be stored
Pyruvate from glycolysis enters the hepatocyte/adipocyte mitochondria
o Pyruvate is converted to acetyl-CoA by pyruvate dehydrogenase (PDH)
o Acetyl-CoA enters the first part of the TCA cycle (see NME 2.31)
o Acetyl-CoA with oxaloacetate is converted to citrate
o Citrate is exported from the mitochondria
Citrate is re-converted to acetyl-CoA and oxaloacetate in the cytoplasm
o Oxaloacetate is converted to malate which re-enters the mitochondria and the TCA cycle
o Acetyl-CoA is converted to malonyl-CoA by acetyl-CoA carboxylase
o Malonyl-CoA is converted into a fatty acid by fatty acid synthase using NADPH
Hormonal control of fatty acid synthesis is through:
o Insulin – activates PDH and acetyl-CoA carboxylase promoting fatty acid synthesis
o Glucagon – inhibits acetyl-CoA carboxylase restricting fatty acid synthesis
Non-hormonal control of fatty acid synthesis is through:
o Citrate – activates acetyl-CoA carboxylase promoting fatty acid synthesis
o Fatty acids – inhibit PDH and acetyl-CoA carboxylase restricting fatty acid synthesis
o NADH – inhibits PDH restricting fatty acid synthesis
LEARNING OUTCOMES
Explain why disorders in glycogen metabolism affect blood glucose homeostasis and cause muscle fatigue
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Liver glycogen stores maintain blood glucose during fasting
o Glycogen releases glucose-6P which is de-phosphorylated to glucose by G6Pase
o G6Pase is only found in the liver
Muscle glycogen stores provide energy during exercise
o Glycogen is metabolised by glycolysis to generate ATP
Disorders of glycogen metabolism:
o Reduce the liver’s ability to replenish blood glucose levels during fasting
o Restrict energy production in muscle leading to fatigue
Explain why the replenishment of glycogen stores is the major priority of glucose metabolism in the liver when
feeding follows a period of fasting
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Glycogen stores are crucial for maintaining blood glucose homeostasis during fasting