REGULATION AND PROPERTIES OF PURIFIED GLUCOSE-6-PHOSPHATE-DEHYDROGENASE FROM RAT-BRAIN

Glucose-6-phosphate dehydrogenase from rat brain was purified 13,000 f old to a specific activity of 480 units/mg protein. The molecular weig ht was 121 kDa. The kinetics of brain glucose-6-phosphate dehydrogenas e are compatible with a model involving two possible states of the enz yme with a low and high affinity for the substrate D-glucose-6-phospha te. NADP(+) and ADP offered protection against p-chloromercuribenzoate inhibition. NADPH is a powerful competitive inhibitor with respect to NADP(+). The apparent K-i for NADPH inhibition was lower than the K-m for NADP(+). ADP inhibited the enzyme competitively with respect to N ADP(+). ATP inhibited the enzyme non-competitively with respect to NAD P(+), whereas kinetics of mixed inhibition was observed with respect t o substrate D-glucose-6-phosphate. The interplay between NADP(+) and N ADPH leading to enzyme activation or inhibition according to their rel ative or absolute concentrations as well as the control of enzyme acti vity by the adenine nucleotide system may contribute a refined mechani sm for the regulation of glucose-6-phosphate dehydrogenase and therefo re the pentose phosphate pathway in brain.