Acetyl-CoA, formed from pyruvate by the action of pyruvate dehydrogenase, is the major substrate for long-chain fatty acid synthesis in nonruminants (Figure 1). (In ruminants, acetyl-CoA is derived directly from acetate.) Pyruvate dehydrogenase is a mitochondrial enzyme, and fatty acid synthesis is in the cytosol; the mitochondrial membrane is impermeable to acetyl-CoA. For acetyl-CoA to be available in the cytosol, citrate is transported from the mitochondrion to the cytosol, then cleaved in a reaction catalyzed by citrate lyase (see Figure 1). Citrate is only available for transport out of the mitochondrion when aconitase is inhibited by its product and therefore saturated with its substrate, so that citrate cannot be channeled directly from citrate synthase onto aconitase. This ensures that citrate is used for fatty acid synthesis only when there is an adequate amount to ensure continued activity of the cycle. The identity and regulation of the many mitochondrial transport systems (eg, malate, citrate, pyruvate) involved in cataplerosis and anaplerosis pathways are poorly understood, but they likely play a critical regulatory role in these pathways.

Fig1. Participation of the citric acid cycle in provision of cytosolic acetyl-CoA for fatty acid synthesis from glucose.

The oxaloacetate released by citrate lyase cannot reenter the mitochondrion, but is reduced to malate, at the expense of NADH, and the malate undergoes oxidative decarboxylation to pyruvate, reducing NADP+ to NADPH. This reaction, catalyzed by the malic enzyme, is the source of half the NADPH required for fatty acid synthesis (the remainder is provided by the pentose phosphate pathway). Pyruvate enters the mitochondrion and is carboxylated to oxaloacetate by pyruvate carboxylase, an ATP-dependent reaction in which the coenzyme is the vitamin biotin.

مواضيع ذات صلة

Glycolysis Can Function Under Anaerobic Conditions

Regulation of the Citric Acid Cycle Depends Primarily on a Supply of Oxidized Cofactors

The Citric Acid Cycle Takes Part in Gluconeogenesis, Transamination, & Deamination

Reactions of The Citric Acid Cycle Generate Reducing Equivalents & CO2

The Citric Acid Cycle Provides Substrates for The Respiratory Chain

Carbohydrates Occur in Cell Membranes & in Lipoproteins

Dyslipidemia and Cardiovascular Risk

Lipoprotein and Lipid Metabolism

Biomedically, Glucose is the Most Important Monosaccharide

Saccharides are Aldehyde or Ketone Derivatives of Polyhydric Alcohols

A Supply of Oxidizable Fuel is Provided in Both The Fed & Fasting States

Many Metabolic Fuels are Interconvertible