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Gluconeogenesis: Animated medical biochemistry
Overview
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Definition: A series of metabolic events that allows for the production of glucose from noncarbohydrate precursors.
Purpose: During fasting, gluconeogenesis becomes the main source of glycemia maintenance after glycogen stores are depleted (after 1–3 days of normal activity)
Cell location: Responsible enzymes are located in cytosol and mitochondria.
Sites of gluconeogenesis
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Primarily carried out in the liver
Renal cortex
Intestinal epithelium
Skeletal muscle cannot participate in gluconeogenesis due to absent glucose-6-phosphatase
Rate-limiting enzyme: fructose-1,6-bisphosphatase
Noncarbohydrate precursors: Glucogenic amino acids (mainly alanine and glutamine), lipids, glycerol, pyruvate, and lactate can all be converted to glucose in an attempt to preserve serum glucose levels. These reactions are energy intensive, as they rely on the consumption of high energy molecules (GTP, ATP).
Primary substrates
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Glucogenic amino acids: Generated from the hydrolysis of protein tissue (typically during fasting), these amino acids are capable of being converted to α-keto acids (e.g., oxaloacetate, α-ketoglutarate) and then to glucose.
Lactate: Via the Cori cycle, lactate produced from anaerobic glycolysis (mostly in skeletal muscle) is shuttled to the liver where it is converted to pyruvate, which serves as the first true substrate in gluconeogenesis.
Propionyl-CoA: Formed from odd-chain fatty acid β-oxidation, this molecule can be carboxylated to form succinyl-CoA. Succinyl-CoA can enter the gluconeogenesis pathway after being converted to oxaloacetate via the TCA cycle.
Glycerol-3-phosphate: released during hydrolysis of triacylglycerols in adipose tissue → blood → liver → phosphorylated by glycerol kinase → oxidized by glycerol phosphate dehydrogenase to dihydroxyacetone phosphate (an intermediate of glycolysis)
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