d-Lactic Acidosis and Selected Cerebellar Ataxias Shelley A. Cross, M.D.  Mayo Clinic Proceedings  Volume 59, Issue 3, Pages 202-205 (March 1984) DOI: 10.1016/S0025-6196(12)60774-5 Copyright © 1984 Mayo Foundation for Medical Education and Research Terms and Conditions

Fig. 1 Diagrammatic representation of pyruvate metabolism. Major pathways of pyruvate formation and breakdown are shown. Words and phrases in parentheses refer to overall pathways. Abbreviations in parentheses refer to specific enzymes: GPT = glutamic-pyruvic transaminase; LDH = lactate dehydrogenase; PC = pyruvate carboxylate; and PDHC = pyruvate dehydrogenase complex. ADP = adenosine diphosphate; ATP = adenosine triphosphate; Pi = inorganic phosphate. (From Blass JP.17 By permission.) Mayo Clinic Proceedings 1984 59, 202-205DOI: (10.1016/S0025-6196(12)60774-5) Copyright © 1984 Mayo Foundation for Medical Education and Research Terms and Conditions

Fig. 2 Overview of pyruvate dehydrogenase complex. Diagram illustrates coordinated action of three enzymes in pyruvate dehydrogenase complex. En1 is pyruvate dehydrogenase, a thiamine pyrophosphate-dependent enzyme that catalyzes decarboxylation of pyruvate to produce CO2 (from the number 1 carbon atom of pyruvate) and active aldehyde (hydroxyethylthiamine). En2 is lipoate acetyltransferase, a lipoic acid-dependent enzyme that catalyzes oxidative transfer of the two-carbon unit from the first enzyme to coenzyme A and forms acetylcoenzyme A. En3 is lipoamide dehydrogenase, a flavin-linked enzyme that reoxidizes lipoic acid to the oxidized form and is itself reoxidized by the oxidized form of nicotinamide adenine dinucleotide (NAD+). Kinase inactivates the complex by catalyzing a phosphorylation of En1. The complex is reactivated by dephosphorylation by a phosphatase. Control of the kinase-phosphatase equilibrium is complex; activation is favored by, among other factors, decrease in the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and an increase in Mg+ + concentration. The products of the reaction, the reduced form of nicotinamide adenine dinucleotide (NADH) and acetylcoenzyme A, are also inhibitors of the pyruvate dehydrogenase complex. FAD = flavin-adenine dinucleotide; FADH2 = reduced form of FAD. (From Blass JP.17 By permission.) Mayo Clinic Proceedings 1984 59, 202-205DOI: (10.1016/S0025-6196(12)60774-5) Copyright © 1984 Mayo Foundation for Medical Education and Research Terms and Conditions