In starv ation, there is ketosis due to –
Correct Answer: Increased b-oxidation
Description: Ans. is 'b' i.e., Increased P-oxidation o Starvation is characterized by decreased insulin : glucagon ratio.o This causesIncreased lipolysis - More FFAs for ketogenesis.Increased p-oxidation - Increased ketogenosis.Decreased oxaloacetate - Acetyl CoA is utilized in ketogenesis.Regulation of ketogenesiso Ketogenesis is regulated at three levels:-Factors regulating mobilization of fatty acids from adipose tissues (i.e. lipolysis):- Free fatty acids, the precursors of ketone bodies, arise from lipolysis of triglycerides in adipose tissue. Hence, factors which enhance lipolysis (e.g. glucagon) stimulate ketogensis by providing more free fatty acids. Conversely, factors that inhibit lipolysis (e.g. insulin) inbibit ketogenesis.Factors regulating b-oxidation of fatty acids:- After uptake by liver, FAAs are either (i) b-oxidized to CO2 or ketone bodies, or (ii> esterified to triacylglycerol. Carnitine acetyl transferase-I (CAT-I) regulates the b-oxidation of fatty acid and therefore the production of starting materials of ketogenesis i.e. acetyl- CoA and acetoacetyl-CoA (The remainder of fatty acids which do not enter b-oxidation, are estesified). Activity of CAT-1 is high in starvation and diabetes leading to increased b-oxidation of fatty acids and increased ketogenesis. CAT-1 activity is low in wrell fed state, resulting in decreased b-oxidation and ketogenesis. This regulation is governed by Malonyl CoA, which is an allosteric inhibitor of carnitine acetyl transferase-I: CAT-1 (or carnitinepalmitoyl transferase-I: (CPT-1). Malonyl CoA is synthesized by acetyl CoA carboxylase. Activity of acetyl CoA carboxylase is high in well fed state due to increase in insulin/glucagon ratio, wrhich intum results in increased formation of malonyl Co.A. Malonyl-CoA inhibits CAT- I (CPT-I) leading to decreased b-oxidation and ketogenesis. Hence, esterification of fatty acids is increased. Conversely, during starvation (and diabetes) insulin/glucagon ratio is decreased which results in decreased activity of acetyl CoA carboxylase and decreased production of malonyl-CoA, releasing the inhibition of CAT-I (CPT-I). This results in increase b-oxidation of fatty acids and ketogenesis.Factors regulating the oxidation of acetyl CoA:- The acetyl-CoA formed in b-oxidation is oxidized in the citric acid cycle, or it enters the ketogenesis to form ketone bodies. When oxaloacetate concentration is low, little acetyl-CoA enters the TCA cycle and ketogenesis is favoured (first reaction of TCA cycle involves oxaloacetate, where it combines with acetyl-CoA to form citrate). Concentration of oxalaceatate is lowered if carbohydrate is unavailable or improperly utilized, e.g. in fasting and in diabetes. This is because of two reasons-In these conditions insulin/glucagon ratio is very low which stimulate gluconeogenesis. Thus, oxaloacetate is utilized in gluconeogenesis and its concentration falls.Due to excessive b-oxidation, more NADH is produced which converts oxaloacetate to malate becauseleads to further decrease in oxaloacetate.# A fall in oxaloacetate concentration causes impairment in TCA cycle as oxaloacetate is involved in first reaction of TCA cycle. Hence, acetyl-CoA is utilized in ketogenesis, instead of entering in TCA cycle.
Category:
Biochemistry
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