Utilization of alpha-keto and alpha-hydroxy analogues of valine by the growing rat

When 70-80-g male albino rats eat a diet furnishing daily requirement of valine for optimal growth (70 mumol/g) and all other nutrients ("complete diet"), they gain weight at an average rate of 3.0 g/100 g body wt/day. When valine is removed, they lose weight at an average 2.1 g/100 g body wt/day. The growth retardation is improved or corrected by adding valine to the diet, daily weight gain being proportional to dietary valine content over a range of 0-70 mumol/g. Addition of alpha-ketoisovaleric acid instead of valine to the valine-free diet also improves or corrects the growth failure. Percent efficiency of alpha-ketoisovaleric acid as a substitute for valine was calculated as: 100 x (micromole valine per gram diet required to produce specified growth response)/(micromole alpha-ketoisovaleric acid per gram diet required to produce the same response). Efficiency of the substitution is inversely related to dietary content of the keto analogue, being 80% when diet contains 17.5 mumol/g (molar equivalent of (1/4) the daily requirement of valine), and 37% when diet provides 140 mumol/g (molar equivalent of twice the daily requirement of valine).alpha-Hydroxyisovaleric acid also substitutes for valine. Efficiency of the substitution at the single ration tested, 70 mumol/g diet, is 45%, similar to that for the keto analogue under the same conditions. When [1-(14)C]alpha-ketoisovaleric acid is injected intravenously, 30-80% of the administered radioactivity is exhaled as (14)CO(2) within 24 h. This finding suggests that inefficiency of alpha-ketoisovaleric acid as a substitute for valine results in part from degradation of the keto acid to isobutyric acid by branched chain dehydrogenase-decarboxylase. Oral administration of neomycin, polymyxin, and bacitracin reduces efficiency of alpha-ketoisovaleric acid as a substitute for valine by (1/4)-(1/2). This effect suggests that transamination of the keto acid may be performed in part by gastrointestinal microbes.