33. This is How We Burn Ketones for Energy
Lesson 33 of Masterclass With Masterjohn: Energy Metabolism
The production of ketones in the liver frees up coenzyme A (CoA) that would otherwise be captured in the accumulating acetyl CoA, and the conversion of acetoacetate to beta-hydroxybutyrate frees up NAD+ that would otherwise be trapped as NADH as the production of NADH in beta-oxidation exceeds that oxidized in the electron transport chain. This allows free CoA and NAD+ to keep beta-oxidation running rapidly. The ketone bodies then traverse through the inner mitochondrial and plasma membranes through the monocarboxylate transporter 1 (MCT1), and possibly through the voltage-dependent anion channel (VDAC) in the outer mitochondrial membrane.
They travel through the blood to ketone-utilizing tissues, where they get into the mitochondria through the same transporters that allowed them to exit the liver. Beta-hydroxybutyrate must be converted to acetoacetate to undergo further metabolism in the ketone-utilizing tissue. Acetoacetate is converted to acetoacetyl CoA using the CoA from succinyl CoA. It is then split to two acetyl CoA by beta-ketothiolase, the same exact enzyme that catalyzes the opposite conversion during ketogenesis.
The acetyl CoA then enters the citric acid cycle. The use of succinyl CoA causes the loss of one ATP that would otherwise have been synthesized in the substrate-level phosphorylation step of the citric acid cycle. Nevertheless, most ATP energy is conserved and ketones represent an efficient means of transporting energy between tissues.
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