Nitric oxide inhibits cardiac energy production via inhibition of mitochondrial creatine kinase

Nitric oxide biosynthesis in cardiac muscle leads to a decreased oxygen con sumption and lower ATP synthesis, It is suggested that this effect of nitri c oxide is mainly due to the inhibition of the mitochondrial respiratory ch ain enzyme, cytochrome c oxidase. However, this work demonstrates that nitr ic oxide is able to inhibit soluble mitochondrial creatine kinase (CK), mit ochondrial CK bound in purified mitochondria, CK in situ in skinned fibres as well as the functional activity of mitochondrial CK in situ in skinned f ibres, Since mitochondrial isoenzyme is functionally coupled to oxidative p hosphorylation, its inhibition also leads to decreased sensitivity of mitoc hondrial respiration to ADP and thus decreases ATP synthesis and oxygen con sumption under physiological ADP concentrations, (C) 1999 Federation of Eur opean Biochemical Societies.