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Thiamin Deficiency: Liver Metabolite Levels and Redox and Phosphorylation States in Thiamin-Deficient Rats¹

National Institute of Mental Health, IR, SMRDN, and National Institute on Alcohol Abuse and Alcoholism, Saint Elizabeth's Hospital, Washington, D. C. 20032, and Department of Biochemistry, University of Nebraska College of Medicine, Omaha, Nebraska 68105

Metabolite concentrations were measured in frozen clamped liver from thiamin-deficient and pair-fed control rats in the fed state and after an 18-hour fast. The fed thiamin-deficient rats showed a significant increase in the concentration of acetoacetate, NH₄⁺, lactate and ADP, and decreases in glutamate, aspartate and -glycerophosphate. Thiamin deficiency resulted in no elevation in either pyruvate or -ketoglutarate in the fed thiamin-deficient animal. The "starved" thiamin-deficient animals were found to have significant increases in concentrations of pyruvate, lactate, -ketoglutarate, citrate, and isocitrate and decreases in aspartate, acetoacetate, ß-hydroxybutyrate and inorganic phosphate. The free mitochondrial [NAD⁺]/[NADH] was elevated in both the fed and "starved" thiamin-deficient groups. The impairment of pyruvate and -ketoglutarate dehydrogenase activity in thiamin deficiency did not invariably lead to elevation in concentration of pyruvate and -ketoglutarate. Thiamin deficiency appeared to cause a decrease in fat stores presumably by diminishing normal postprandial fat synthesis. Fat synthesis from glucose would be impaired in thiamin deficiency by:

a) decreased activity of pyruvate and -ketoglutarate dehydrogenases,

b) diminished pyruvate carboxylase activity and

c) decreased transketolase activity leading to a decreased ability of the cell to form NADPH necessary in the reductive synthesis of fatty acid.

KEY WORDS: • thiamin deficiency • metabolites • redox ratios • phosphorylation states • liver

¹ Supported in part by Army Research Grant DAHC 19-68 G0089.

² Present address: Biochemical Toxicology, Division of Toxicology, Office of Science, Food and Drug Administration, Washington, DC 20204.

Manuscript received 5 July 1972.