In a well fed state, the activity of CPT-I in outer mitochondrial membrane is inhibited by:
Correct Answer: Malonyl CoA
Description: Ans is 'd' i.e. Malonyl CoA "Malonyl-CoA, the initial intermediate in fatty acid biosynthesis formed by acetyl-CoA carboxylase in the fed state, is a potent inhibitor of CPT-I"Carnitine palmitoyl transferase I (CPT-I) is the rate limiting enzyme in the process of beta-oxidation of fatty acids.Beta-oxidation is the process by which fatty acids, in the form of Acyl-CoA molecules, are broken down in mitochondria to generate Acetyl-CoA.Under normal conditions, acetyl-CoA is further oxidized in the citric acid cycle (TCA cycle) to produce energy. However, if the amounts of acetyl-CoA generated in fatty-acid b-oxidation challenge the processing capacity of the TCA cycle or if activity in the TCA cycle is low due to low amounts of intermediates such as oxaloacetate, acetyl-CoA is then used instead in biosynthesis of ketone bodies via acetoacyl-CoA and b-hydroxy-b-methylglutaryl-CoA (HMG- CoA).Beta-oxidation of fatty acids is caused when there is low blood glucose levels in the blood, after exhaustion of cellular carbohydrate stores, such as glycogen. In well fed state fatty acids are esterified.The entry of fatty acids into the oxidative pathway is regulated by carnitine palmitoyltransferase-I (CPT-I).In a well fed state the CPT-I activity is low, leading to depression of fatty acid oxidation. In state of starvation, CPT-I activity is high, leading to fatty acid oxidation.CPT-I is inhibited by Malonyl-CoA.Malonyl-CoA is the initial intermediate in fatty acid biosynthesis formed by acetyl-CoA carboxylase in the fed state.In well fed state, free fatty acids are nearly all esterified to acylglycerols.In starvation Acetyl-CoA carboxylase is inhibited directly by acyl-CoA, and malonyl-CoA decreases, releasing the inhibition of CPT-I and allowing more acyl-CoA to be beta-oxidized.Thus, beta-oxidation from free fatty acids is controlled by the CPT-I gateway into the mitochondria, and the balance of the free fatty acid uptake not oxidized is esterified.Role of Carnitine palmitoyl transferase I in fatty acid oxidation: The inner mitochondrial membrane is impermeable to fatty acids. CPT-I helps in the transport of fatty acids into the mitochondria.
Category:
Biochemistry
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