Competition for NADH by mitochondrial dehydrogenases in rat and guinea pig livers.

M Jomain-Baum,K Ogata,S Weinhouse,R.W Hanson

doi:10.1016/s0021-9258(17)38051-1

M Jomain-Baum, K Ogata + Show 2 more

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https://doi.org/10.1016/s0021-9258(17)38051-1

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Abstract

The factors responsible for regulating the NAD+/NADH ratio of guinea pig and rat liver mitochondria were studied using both isolated mitochondria and perfused livers from both species. A comparison of the rates of ketone body formation and the acetoacetatelfi-hydroxybutyrate ratio in isolated guinea pig and rat liver mitochondria in State 3 show that in the absence of added citric acid cycle anions, mitochondria from both species will synthesize predominantly acetoacetate. Rat liver mitochondria produced 4 times more total ketone bodies than guinea pig liver mitochondria. The addition of malate dramatically reduced the formation of ketone bodies by supplying oxalacetate for the subsequent synthesis of citrate by mitochondria from both species. The only experimental treatment that reduced the acetoacetatelp-hydroxybutyrate ratio during State 3 in guinea pig liver mitochondria, to levels noted in mitochondria from rat liver, was

Highlights

MIREILLE JOMAIN-BAUM, From the Fels Research Medicine, Philadelphia, KORECHIKA OGATA,$ SIDNEY WEINHOUSE, Institute and the Department of Biochemistry, Pennsylvania 1914b
Our results indicate that P-hydroxybutyrate dehydrogenase in rat liver is an important mechanism for balancing the mitochondrial ratio during periods of fatty acid oxidation, since the reduced product of the reaction, P-hydroxybutyrate can be released from the liver
The rate of P-enolpyruvate synthesis by guinea pig liver mitochondria is inhibited by 60% when cycloheximide is added to block Site 1 and reduce ATP formation [27]

Summary

The abbreviations used are

Guinea pig liver P-hydroxybutyrate dehydrogenase, on the other hand, is unable to maintain NADH ratio of the mitochondria, equilibrium presumably with the NAD+/ owing to its low activity in this species This lack of equilibrium of the enzyme in competition with other, more active mitochondrial dehydrogenases, may explain the shift toward oxidation noted in the freeze-clamped importantly, guinea pig liver in previous studies. More it indicates that guinea pig liver lacks an important mechanism for balancing its mitochondrial oxidationreduction state and further supports the need for a more critical assessment of a wider variety of mammalian species in the future formulation of regulatory models

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