10 Carbohdrates - Glycolysis Lactate-1

10 Carbohdrates - Glycolysis Lactate-1 - Carbohydrates:...

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Carbohydrates: Glycolysis Lactate Metabolism HNFE 3025 Fall 2009
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Metabolic Fates of Monosaccharides 2 Fig. 3-12, p. 78
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Anaerobic Glycolysis Catabolism of glucose to lactate (pyruvate) Fructose and Galactose are primarily metabolized in the liver 3 Fig. 3-17, p. 83
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Stages of Glycolysis Priming stage Hexokinase (Glucokinase) – ATP – ATP Second stage – Splitting Aldolase and triose phosphate isomerase Third Stage – Reducing and Oxidizing Glyceraldehyde 3-phosphate dehydrogenase + 2 NADH Phosphoglycerate kinase + 2 ATP Phosphoglycerate mutase Enolase Pyruvate kinase + 2 ATP 4
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Glucose Phosphorylation A class of enzymes, the Hexokinases (HK) catalyze the phosphorylation of glucose. Glucose + ATP Glucose-6-phosphate + ADP Phosphorylation of glucose traps it inside the cell 4 hexokinase isoenzymes (isozymes) vary in cellular location and kinetics – HK I, II, III have low K m values (0.02-0.13 mM) – HK IV (glucokinase) has a high K m ~5-8 mM 5 HK
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Hexokinases HK I, II, III Constitutive enzymes HK I – found in all mammalian tissues and considered a "housekeeping enzyme" – It is unaffected by most physiological, hormonal, and metabolic changes HK II – principal substrate regulated isoform in many cell types Inhibited by the product of their reaction – G 6-P. Can also phosphorylate fructose HK IV (glucokinase) is located primarily in the liver and β -cells of pancreas Highly inducible (by insulin) Not allosterically modified by G 6-P 6
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Glucokinase (GK): A Special Case 2 mechanisms for regulation GKRP (glucokinase regulatory protein) When bound to GKRP, GK is inactive Binds when glucose content is low (post-absorptive or fasting state) Following a meal (glucose and fructose are available), GK is released from GKRP GK is also induced by insulin Transcription control Its cellular concentration reflects CHO content of diet GK is not inhibited by G 6-P increase 7
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Priming/Splitting Stages of Glycolysis 8 PFK1 reaction is rate-limiting step or Committed Step
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Redox Stage 9 Lactate + + lactate dehydrogenase
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When Would We Want Glycolysis to be Active? Liver: When a person’s diet is consistently high in CHO Following a CHO-rich meal Skeletal Muscle: When blood glucose is high following a CHO-rich meal When muscle is active and there are large stores of glycogen, or small stores of glycogen, but the intensity of activity is high 10
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Enzyme Regulation Substrate Availability In glycolysis ADP is a substrate for phosphoglycerate kinase and pyruvate
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10 Carbohdrates - Glycolysis Lactate-1 - Carbohydrates:...

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