METABOLISM OF VALINE IN CULTURED HUMAN-SKIN FIBROBLASTS

1. 1. The pathway of valine metabolism in human cultured skin fibroblasts has been explored with the use of 14C differentially labeled substrates. These include [1-14C]valine, DL-[2-14C]valine, DL-[4-14C]valine, and [1-14C]isobutyric, [2-14C]isobutyric, [1-14C]propionate and 2[-Me-14C]methylmalonic acids. The rates of 14CO2 production in cells derived from normal individuals and from patients affected with propionic acidemia and methylmalonic aciduria were compared. 2. 2. Results showed that nearly normal amounts of labeled CO2 were liberated using [2-14C]valine and [1-14C]isobutyric acid by patient cells. Additional studies have suggested that the pathway of valine metabolism is via propionyl-CoA as an obligated intermediate presumably derived from methylmalonyl semialdehyde, rather than the direct conversion of methylmalonyl semialdehyde tomethylmalonyl-CoA without the participation of propionate. 3. 3. Substantial amounts of labeled intermediate, β-hydroxyisobutyric acid were detected in all valine and isobutyrate incubations. These findings suggest that the conversion of β-hydroxyisobutyrate to methylmalonyl semialdehyde, a NAD-dependent reaction, is the rate-limiting step of valine metabolism. © 1979.