VITAMINS

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Two siblings with dihydropteridine reductase (DHPR) deficiency were examined, who showed convulsions and severe mental retardation despite dietary control of blood phenylalaninemia. The patients showed low levels of 5-hydroxyindole-acetic acid, homovanilic acid and folate in cerebrospinal fluid, which accounts for their neurological damage. Early diagnosis of hyperphenylalaninemia due to tetrahydrobiopterin (BH_4) deficinecy is very important, because their treatment is different from that of classic phenylketonuria. We developed two diagnostic methods for BH_4 deficiency. One is a method for assaying DHPR in dried blood spots on filter papters. Another is a high-performance liguid chromatographic assay for the measurement of various forms of pterins in filter paper spots of urine. A newborn infant with multiple carboxylase deficinecy was observed with tachypnea, seizures and metabolic ketoacidosis. The organic acid pattern was consistent with deficient in vivo activity of at least three biotin-dependent carboxylases: propionyl CoA carboxylase (PCC), methylcrotnyl CoA carboxylase (MCC), pyruvate carboxylase (PC). An administration of pharmacologic doses of biotin resulted in immediate improvement from the clinical and metabolic status. Fibroblasts from the patient were found to have deficient acitvities of PCC, MCC, PC and acetyl CoA carboxylase (ACC) and have abnormal holocarboxylase synthetase (HCS) activity with a highly elevated Km for biotin. These results show that the primary defect is in HCS. A deficiency of ACC, a cytosolic enzyme, besides mitochondrial carboxylase suggests that at least a common subunit of the HCS system is shared by mitochondria and cytosol in humans.

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3-Acetylpyridine (3-AP), an antagonist of nicotinic acid was given to suckling rats of 6 days of age. Rats were killed on 6, 10, 15, 19, 24, 27 and 30 days of age. The quantity of myelin, cerebroside and DNA in brain, and the concentration of thyroid hormon in serum were determined for in rats receiving 3-AP as well as for those of pair-fed and ad libitum control. The experimental animals showed lower values in yield of myelin, content of cerebroside and activity of 2', 3'-cyclic nucleotide-3-phosphohydrolase (CNP) than those of pair-fed and ad libitum control animals. Whereas, rats receiving 3-AP and pair-fed control, showed lower values in quantity of DNA in brain and concentration of thyroid hormon in serum, when compared with ad libitum control. These results indicate that 3-AP plays some role in the loss of myelin rather than in development of undernourishment due to restricted food intake. Our observations suggest that nicotinic acid may influence myelination through the metabolism of cerebroside which contains long-chain fatty acids.

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The origin of methyl group (C-8) attached to C-2 of the pyrimidine moiety in procaryotes, and the precursor of the C-2 and C-8 atoms in eucaryotes on thiamin biosynthesis have not yet been established. Johnson et al. and Tomlinson had reported the incorporation of acetate into the pyrimidine moiety in Saccharomyces cerevisiae and Bacillus subtilis. We investigated the incorporation of acetate into the pyrimidine moiety in Esherichia coli and S. cerevisiae. The results obtained showed that acetate neither incorporated into the pyrimidine nor the thiazole moiety. We furthermore studied the incorporation of glycerol, pyruvate and alanine into the thiazole moiety in E. coli and S. cerevisiac. Glycerol and pyruvate but not alanine were incorporated into the thiazole moiety in E. coli. However in S. cerevisiae, incorporation of alanine that had been reported by Johnson and others was not observed.

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