Utilization of a - Keto and a - Hydroxy Analogues of Valine by the Growing Rat

diet furnishing daily requirement of valine for optimal growth (70 iumol/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 /%mol/g. Addition of a-ketoisovaleric acid instead of valine to the valine-free diet also improves or corrects the growth failure. Percent efficiency of a-ketoisovaleric acid as a substitute for valine was calculated as: 100 X (micromole valine per gram diet required to produce specified growth response)/(micromole a-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 iumol/g (molar equivalent of I the daily requirement of valine), and 37% when diet provides 140 .mol/g (molar equivalent of twice the daily requirement of valine) . a-Hydroxyisovaleric acid also substitutes for valine. Efficiency of the substitution at the single ration tested, 70 Amol/g diet, is 45%, similar to that for the keto analogue under the same conditions. When [1-"C]a-ketoisovaleric acid is injected intravenously, 30-80% of the administered radioactivity is exhaled as 14CO2 within 24 h. This finding suggests that inefficiency of a-ketoisovaleric acid as a substitute for valine results in part from degradation of the keto acid to isobutyric acid by branched chain dehydrogenasedecarboxylase. Oral administration of neomycin, polymyxin, and bacitracin reduces efficiency of a-ketoisovaleric acid as a substitute for valine by -. This effect suggests that Received for publication 19 December 1973 and in revised form 7 March 1974. transamination of the keto acid may be performed in part by gastrointestinal microbes.