STIMULATION OF BRAIN ACETYL‐CoA HYDROLASE BY ATP AND ATP ANALOGUES

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Abstract
—: The effects of ATP and ATP analogues on the brain acetyl‐CoA hydrolase (EC 3.1.2.1) were studied. The enzyme was stimulated reversibly by ATP‐Mg2+ the presence of Mg2+ being absolutely required for the stimulation. The stimulatory effect of ATP was highly specific since adenine nucleotides other than ATP had no stimulatory effects and nucleoside triphosphates other than ATP stimulated the enzyme much less than ATP in the following order: ATP > ITP CTP, UTP GTP. A phosphate modified analogue of ATP, AMP‐PNP had a similar stimulatory effect to that of ATP. Other ATP analogues such as AMP‐PCP and AMPCPP showed less stimulatory effect than ATP. The order of the stimulatory effects of these ATP analogues was: ATP > AMP‐PNP > AMP‐PCP > AMPCPP. The concentrations needed for half‐maximal stimulation of ATP, AMP‐PNP and AMP‐PCP were approx 0.11 mm, 0.22 mm, and 0.22 mm, respectively. Double reciprocal plots demonstrated that ATP as well as AMP‐PNP produced a significant decrease in the apparent Km, value for acetyl‐CoA and an increase in Vmax indicating that these nucleotides increased the affinity for acetyl‐CoA through binding at a site other than the catalytic site. The data described above suggest that the rate of hydrolysis of acetyl‐CoA may be regulated by the concentration of ATP in the micro‐environment of the enzyme.