Mitochondria from the left heart ventricles of both normotensive and spontaneously hypertensive rats oxidize externally added NADH mostly via a novel malate/oxaloacetate shuttle as reconstructed in vitro.
A substantial increase in NADH production, arising from accelerated glycolysis, occurs in cardiac hypertrophy and this raises the question of how the NADH is oxidised. We have addressed this problem by reconstructing appropriate mitochondrial shuttles in vitro, using mitochondria from the left ventricles of both normotensive and spontaneously hypertensive rats at 5 and 24 weeks of age as model systems for left ventricle hypertrophy and hypertrophy/hypertension respectively. We found that most NADH oxidation occurs via a novel malate/oxaloacetate shuttle, the activity of which increases with time and with the progression of hypertrophy and development of hypertension as judged by statistical ANOVA analysis. In contrast, alpha-glycerol-phosphate and the malate/aspartate shuttles were shown to make only a minor contribution to NADH oxidation in a manner essentially independent of age and progression of hypertrophy/hypertension. The rate of malate transport in exchange with oxaloacetate proved to limit the rate of NADH oxidation via this malate/oxaloacetate shuttle.
Atlante
Anna
A
Istituto di Biomembrane e Bioenergetica, CNR, Bari, Italy.
Seccia
Teresa M
TM
De Bari
Lidia
L
Marra
Ersilia
E
Passarella
Salvatore
S
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001794:Blood Pressure; D005994:Glycerophosphates / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000378:metabolism; D008293:Malates / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D008954:Models, Biological; D008956:Models, Chemical; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D062907:Oxaloacetic Acid / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013223:Statistics as Topic
D005994:Glycerophosphates; D008293:Malates; D009243:NAD; D062907:Oxaloacetic Acid; D001224:Aspartic Acid; D009249:NADP; D008291:Malate Dehydrogenase