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Effect of Hypothyroidism on Methylmalonate Excretion and Hepatic Vitamin B-12 Levels in Rats¹

Department of Nutritional Sciences, University of California, Berkeley, CA 94720

The effect of hypo- and hyperthyroidism on vitamin B-12 metabolism in the rat was studied by measuring methylmalonic acid excretion, B-12 content of liver and oxidation of 2-[¹⁴C]histidine. Ten percent pectin was added to increase severity of B-12 deficiency. The addition of thiouracil to a diet containing 10% pectin decreased the excretion of methylmalonic acid suggesting an amelioration of the B-12 deficiency. It was found that part of this decreased methylmalonic acid excretion was due to a decreased food consumption with a correspondingly decreased intake of branched-chain amino acids which are precursors of methylmalonic acid. When attempts were made to increase the protein intake of animals receiving thiouracil so their amino acid intake was equal to that of the control animals, methylmalonic acid excretion was still lower than that of the controls. It was also found that the vitamin B-12 content of the liver was higher in the animals receiving thiouracil than in the controls. Thyroidectomy had the same effect as feeding thiouracil. Liver B-12 levels are rapidly depleted on a B-12 deficient diet containing 10% pectin. It appears that hypothyroidism, induced either by thyroidectomy or by feeding thiouracil, slows the rate of depletion of hepatic B-12 which in turn facilitates the metabolism of methylmalonic acid and decreases its excretion in the urine.

KEY WORDS: • vitamin B-12 • methylmalonic acid • thiouracil • hypothyroidism • rats

¹ Supported in part by U.S. Public Health Service Grant No. Am-08171 from the National Institutes of Health.

² To whom reprint requests should be sent.

³ Present address: Biochemistry Division, Bhabha Atomic Research Center, Bombay 400 085, India.

Manuscript received 2 February 1988. Revision accepted 8 August 1988.