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1. A newly developed biotin assay was used to monitor plasma and urinary biotin concentration after the oral administration of biotin. 2. In two normal subjects, leucocyte propionyl-CoA carboxylase and β-methylcrotonyl-CoA carboxylase were markedly stimulated after the administration of biotin.

1. Five-carbon-atom organic acids (C-5 acids) have been administered intravenously to rabbits with ventriculocisternal perfusion and continuous electroencephalographic recording (EEG). The concentration of the acids in the cerebrospinal fluid (CSF) perfusate have been compared with changes in integrated low-frequency activity in the EEG. 2. The C-5 acids investigated were those accumulating in inborn errors of metabolism, i.e. isovaleric acid, ß-methylcrotonic acid, tiglic acid and a-keto- and a-hydroxy-isovaleric acid. Their activity was compared with that of valeric acid. 3. Valeric acid and isovaleric acid produced coma and pronounced increase in slow-wave electrical activity and these changes paralleled the increase in concentration of the acids in the CSF perfusate. 4. The concentration of ß-methylcrotonic acid and tiglic acid in the CSF perfusate reached values comparable with valeric acid and isovaleric acid but showed less encephalopathic activity. An interaction between ß-methylcrotonic acid and isovaleric acid was observed. 5. Although the concentrations of a-ketoisovaleric acid and a-hydroxyisovaleric acid rose to the lesser extent in the CSF perfusate, changes in reusability of the animal and in the EEG recording were demonstrated. 6. It is concluded that all the C-5 acids tested have encephalopathic activity although this is lessened by the presence of either a double bond or an oxygenated functional group.

1. The case is described of a child with retarded physical and mental development, recurrent megaloblastic anaemia, methylmalonic aciduria and abnormal homocysteine metabolism resulting from an inborn error in the metabolism of cobalamins. She died at the age of 7 years. At autopsy there was pulmonary fibrosis and the brain showed lesions typical of those seen in subacute combined degeneration of the cord. 2. A metabolic abnormality was present which resulted in an inability to maintain normal tissue concentrations of the two coenzyme forms of vitamin B12, methylcobalamin and adenosylcobalamin. Lack of methylcobalamin led to deficient activity of N5-methyltetrahydrofolate-homocysteine methyltransferase with reduced ability to methylate homocysteine, and lack of adenosylcobalamin to deficient activity of methylmalonyl-CoA mutase, which accounted for the methylmalonic aciduria. 3. Analyses of total vitamin B12 and of individual cobalamins by a chromatobioautographic technique showed that in organs sampled at autopsy, the content of total vitamin B12 and of methylcobalamin, adenosylcobalamin and hydroxocobalamin were all greatly reduced. The plasma had a high normal total vitamin B12 content, but showed a gross abnormality in the distribution of individual cobalamins, methylcobalamin being decreased and adenosylcobalamin and hydroxocobalamin increased. The erythrocytes showed a reduction in cobalamins resembling that in the solid organs, though less severe. 4. The underlying abnormality in this patient appeared to be either a defect in cellular uptake of vitamin B12, or a defect in a metabolic pathway leading to the formation of a common precursor of methylcobalamin and adenosylcobalamin. Abnormalities in transcobalamins I and II, plasma factors involved in plasma transport and cellular uptake of vitamin B12, were excluded. 5. The clinical and biochemical findings in the patient are compared with those described in three patients previously reported, who had methylmalonic aciduria and homocystinuria, and who were in some respects similar to this patient. The present case is unusual in that previous examples of errors in cobalamin metabolism have not had megaloblastosis or neurological changes typical of vitamin B12 deficiency. It is also the first case in which direct estimations of individual cobalamins have been made.

In the female but not the male rat, the effect which gonadectomy has on the weight of the adrenal glands is conditioned by the functional state of the gonads at the time of their removal.

Oestradiol dipropionate enhances the effect of both endogenous and exogenous adrenocorticotrophic hormone (ACTH) on the weight of the adrenal glands of the male rat. Methyl testosterone has the opposite effect. It is concluded that sex hormones exert their effect by modifying both hypophysial secretion of ACTH and adrenocortical sensitivity to ACTH.

A new assay for leucocyte methylmalonyl CoA mutase is described. The [14C]-succinate produced in this assay is separated from the substrate [14C]methylmalonate by semi-preparative gas chromatography. The efficiency of this separation has allowed a linear assay of enzyme activity to be developed. Using saturating concentrations of coenzyme B12this enzyme has been measured in the leucocytes from two children with different forms of congenital methylmalonicaciduria.