Physiological implications of the substrate specificities of acetohydroxy acid synthases from varied organisms.
Acetohydroxy acid synthase (AHAS; EC 4.1.3.18) catalyzes the following two parallel, physiologically important reactions: condensation of two molecules of pyruvate to form acetolactate (AL), in the pathway to valine and leucine, and condensation of pyruvate plus 2-ketobutyrate to form acetohydroxybutyrate (AHB), in the pathway to isoleucine. We have determined the specificity ratio R with regard to these two reactions (where VAHB and VAL are rates of formation of the respective products) as follows: VAHB/VAL = R [2-ketobutyrate]/[pyruvate] for 14 enzymes from 10 procaryotic and eucaryotic organisms. Each organism considered has at least one AHAS of R greater than 20, and some appear to contain but a single biosynthetic AHAS. The implications of this for the design of the pathway are discussed. The selective pressure for high specificity for 2-ketobutyrate versus pyruvate implies that the 2-ketobutyrate concentration is much lower than the pyruvate concentration in all these organisms. It seems important for 2-ketobutyrate levels to be relatively low to avoid a variety of metabolic interferences. These results also reinforce the conclusion that biosynthetic AHAS isozymes of low R (1 to 2) are a special adaptation for heterotrophic growth on certain poor carbon sources. Two catabolic "pH 6 AL-synthesizing enzymes" are shown to be highly specific for AL formation only (R less than 0.1).
Gollop
N
N
Department of Biology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Damri
B
B
Chipman
D M
DM
Barak
Z
Z
D000095:Acetolactate Synthase / Q000032:analysis / Q000502:physiology*; D002087:Butyrates / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007652:Oxo-Acid-Lyases / Q000502:physiology*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013379:Substrate Specificity
D002087:Butyrates; D011773:Pyruvates; C005087:alpha-ketobutyric acid; D019289:Pyruvic Acid; D000095:Acetolactate Synthase; D007652:Oxo-Acid-Lyases