REGULATION OF FATTY-ACID BETA-OXIDATION IN RAT-HEART MITOCHONDRIA

被引:42
作者
WANG, HY [1 ]
BAXTER, CF [1 ]
SCHULZ, H [1 ]
机构
[1] CUNY CITY COLL,DEPT CHEM,CONVENT AVE & 138TH ST,NEW YORK,NY 10031
关键词
D O I
10.1016/0003-9861(91)90472-U
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In an attempt to elucidate the mechanism by which the rate of fatty acid oxidation is tuned to the energy demand of the heart, the effects of changing intramitochondrial ratios of [acetyl-CoA] [CoASH] and [NADH] [NAD+] on the rate of β-oxidation were studied. When 10 mm l-carnitine was added to coupled rat heart mitochondria to lower the ratio of [acetyl-CoA] [CoASH], the rate of palmitoylcarnitine β-oxidation, as measured by the formation of acid-soluble products, was stimulated more than fourfold at state 4 respiration while β-oxidation at state 3 respiration was hardly affected. Neither oxaloacetate nor acetoacetate, added to mitochondria to lower the [NADH] [NAD+] ratio, stimulated β-oxidation. Rates of respiration at states 3 and 4 were unchanged by additions of l-carnitine, oxaloacetate, or acetoacetate. Determinations of intramitochondrial ratios of [acetyl-CoA] [CoASH] by high performance liquid chromatography yielded values close to 10 for palmitoylcarnitine-supported respiration at state 4 and 2.5 at state 3 respiration. Addition of 10 mm l-carnitine caused a dramatic decrease of these ratios to less than 0.2 at both respiration states. Studies with purified or partially purified enzymes revealed strong inhibitions of 3-ketoacyl-CoA thiolase by acetyl-CoA and of l-3-hydroxyacyl-CoA dehydrogenase by NADH. Moreover, the activity of 3-ketoacyl-CoA thiolase at concentrations of acetyl-CoA and CoASH prevailing at state 3 respiration was 4 times higher than its activity in the presence of acetyl-CoA and CoASH observed at state 4. Altogether, this study leads to the conclusion that the rate of β-oxidation in heart can be regulated by the intramitochondrial ratio of [acetyl-CoA] [CoASH] which reflects the energy demand of the tissue. The thiolytic cleavage catalyzed by 3-ketoacyl-CoA thiolase may be the site at which β-oxidation is controlled by the [acetyl-CoA] [CoASH] ratio. © 1991.
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页码:274 / 280
页数:7
相关论文
共 17 条
[1]   FACTORS CONTROLLING RATE OF FATTY-ACID BETA-OXIDATION IN RAT-LIVER MITOCHONDRIA [J].
BREMER, J ;
WOJTCZAK, AB .
BIOCHIMICA ET BIOPHYSICA ACTA, 1972, 280 (04) :515-530
[2]  
CHAPPELL JB, 1969, SUBCELLULAR COMPONEN, P77
[3]   SEPARATION, PROPERTIES, AND REGULATION OF ACYL COENZYME-A DEHYDROGENASES FROM BOVINE HEART AND LIVER [J].
DAVIDSON, B ;
SCHULZ, H .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1982, 213 (01) :155-162
[4]   TISSUE SULFHYDRYL GROUPS [J].
ELLMAN, GL .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1959, 82 (01) :70-77
[5]  
GOLDMAN P, 1961, J BIOL CHEM, V236, P2620
[6]  
GORNALL AG, 1949, J BIOL CHEM, V177, P751
[7]  
HANSFORD RG, 1975, J BIOL CHEM, V250, P8361
[8]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265
[9]   ENZYMES OF FATTY ACID METABOLISM [J].
LYNEN, F ;
OCHOA, S .
BIOCHIMICA ET BIOPHYSICA ACTA, 1953, 12 (02) :299-314
[10]  
LYSIAK W, 1988, J BIOL CHEM, V263, P1151