Free fatty acids influx

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts the enzyme from an inactive dimer to an active polymeric form, having a molecular mass of several milhon. Inactivation is promoted by phosphorylation of the enzyme and by long-chain acyl-CoA molecules, an example of negative feedback inhibition by a product of a reaction. Thus, if acyl-CoA accumulates because it is not esterified quickly enough or because of increased lipolysis or an influx of free fatty acids into the tissue, it will automatically reduce the synthesis of new fatty acid. Acyl-CoA may also inhibit the mitochondrial tricarboxylate transporter, thus preventing activation of the enzyme by egress of citrate from the mitochondria into the cytosol. 

Figure 29.3 Summary diagram of major impacts of ethanol on metabolic pathways. An influx of ethanol disturbs the balance of carbohydrate and fatty acid metabolism. As a result of the oxidation of ethanol, concentrations of NADH and acetyl CoA are increased. Steps in the tricarboxylic acid cycle (TCA) and the mitochondrial pathway for p-oxidatlon of free fatty acids (FFA) which produce these species are inhibited (blue). At the same time, the excess amounts of NADH and acetyl CoA create conditions in which the fatty add synthesis and acidosis are favoured (red). The abundance of acetyl CoA means alcohol precursor metabolites accumulate. See text for a detailed explanation. Abbreviations ADH, alcohol dehydrogenase MEOS, microsomal endoplasmic oxidising system ALD, aldehyde dehydrogenase TG, triglycerides TCA, tricarboxylic acid cycle FFA, free fatty adds.

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