Figure 9.

Pathways of intermediary metabolism in liver and muscle. In the fed state, glucose-derived pyruvate serves as a principal source of acetyl-CoA. In the fasted state, pyruvate is conserved for alanine synthesis (muscle), anaplerotic entry into the TCA cycle (muscle), and gluconeogenesis (liver). Long-chain fatty acids, branched-chain amino acids, and ketones provide alternative sources of acetyl-CoA. Transport of fatty acids into the mitochondria requires CPT1-mediated conversion of cytosolic fatty acyl-CoAs to acylcarnitines, which are converted back to acyl-CoA on the matrix side of the inner mitochondrial membrane. Long-, medium- and short-chain acyl-CoA intermediates of fuel oxidation give rise to acylcarnitine metabolites [e.g., C16, C8, C5, C4OH, C4-DC, C2 (in green)] that are recycled or exported from the tissue. Use of amino acids as oxidative or gluconeogenic substrates requires aminotransferases such as GOT and TAT, which use αKG to generate glutamate, glutamine, and NH₄⁺ as nitrogen precursors of liver ureagenesis (yellow box). Liver-specific pathways are denoted in blue. Dashed lines represent multistep reactions. Pathways: β-ox, β-oxidation; TCA, tricarboxylic acid cycle. Enzymes: CPT1, carnitine palmitoyltransferase 1; GOT1, cytosolic aspartate aminotransferase; GOT2, mitochondrial aspartate aminotransferase; IVD, isovaleryl-CoA dehydrogenase; TAT, tyrosine aminotransferase. Metabolites: aKG, alpha ketoglutarate; βHB, β-hydroxybutyrate; leu/isoleu, leucine/isoleucine; OAA, oxaloacetate; suc-CoA, succinyl coA.