Rapid oxidation of NADPH via the reconstituted malate-aspartate shuttle in systems containing mitochondrial and soluble fractions of rat liver: implications for ethanol metabolism.
In an attempt to assess whether hydrogen shuttle capacity might serve as the rate-limiting factor in the hepatic oxidation of ethanol, the malate-aspartate shuttle was reconstituted in systems containing mitochondrial and soluble fractions of rat liver. Oxidation of NADH was stimulated slightly by the addition of either glutamate or malate but when both substrates were added the stimulation was far stronger. This effect was greatly enhanced by aspartate indicating that, when not added to the system, extramitochondrial aspartate was limiting. It was found that the rate of oxidation of NADH was directly related to the amount of mitochondrial protein present but extramitochondrial reactions became restrictive when the 'soluble protein/mitochondrial protein' ratio fell below 0.8. When calculated on a whole tissue basis the maximum rate of oxidation of NADH by the reconstituted shuttle was substantially higher than reported rates of ethanol oxidation in vivo. The results are discussed in relation to the normal control of ethanol metabolism.
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008293:Malates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D008293:Malates; D011506:Proteins; D009243:NAD; D001224:Aspartic Acid; D000431:Ethanol