PYRUVATE CARBOXYLATION PREVENTS THE DECLINE IN CONTRACTILE FUNCTION OF RAT HEARTS OXIDIZING ACETOACETATE

被引:96
作者
RUSSELL, RR [1 ]
TAEGTMEYER, H [1 ]
机构
[1] UNIV TEXAS, SCH MED, DEPT MED, DIV CARDIOL, 1631 FANNIN, HOUSTON, TX 77030 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1991年 / 261卷 / 06期
关键词
ANAPLEROSIS; NADP+-DEPENDENT MALIC ENZYME; TRICARBOXYLIC ACID CYCLE;
D O I
10.1152/ajpheart.1991.261.6.H1756
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Acetoacetate, when present as the only fuel for respiration in rat hearts, causes an impairment in contractile function that is reversible with the addition of substrates that can contribute to anaplerosis. To determine the importance of pyruvate carboxylation via NADP+-dependent malic enzyme on metabolism and function in hearts oxidizing acetoacetate, isolated working rat hearts were perfused with [1-C-14]pyruvate and acetoacetate. While the cardiac power output after 60 min of perfusion in hearts utilizing acetoacetate alone had fallen to 44% of the initial value, the addition of pyruvate resulted in a stable performance with no fall in the work output. When hydroxymalonate, an inhibitor of NADP+-dependent malic enzyme and malate dehydrogenase, was added to the two substrates, function at 60 min was similar to the value for hearts oxidizing acetoacetate alone. Measurements of the specific activities of malate, aspartate, and citrate confirm inhibition of both pyruvate carboxylation and malate oxidation. The findings are consistent with a mechanism in which the enrichment of malate by pyruvate improves function by increasing the production of reducing equivalents by the malate dehydrogenase and the isocitrate dehydrogenase reactions increase flux through the span of the tricarboxylic acid cycle from malate to 2-oxoglutarate. The present study demonstrates the physiological importance of anaplerotic pathways in maintaining contractile function in the heart.
引用
收藏
页码:H1756 / H1762
页数:7
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共 35 条
  • [1] THE EVOLUTION OF METABOLIC CYCLES
    BALDWIN, JE
    KREBS, H
    [J]. NATURE, 1981, 291 (5814) : 381 - 382
  • [2] Bergmeyer HI., 1974, METHODS ENZYMATIC AN
  • [3] BOWMAN RH, 1966, J BIOL CHEM, V241, P3041
  • [4] KETONE-BODIES MAINTAIN NORMAL CARDIAC-FUNCTION AND MYOCARDIAL HIGH-ENERGY PHOSPHATES DURING INSULIN-INDUCED HYPOGLYCEMIA INVIVO
    BREUER, J
    CHUNG, KJ
    PESONEN, E
    HAAS, RH
    GUTH, BD
    SAHN, DJ
    HESSELINK, JR
    [J]. BASIC RESEARCH IN CARDIOLOGY, 1989, 84 (05) : 510 - 523
  • [5] PYRUVATE-CARBOXYLASE AND PROPIONYL-COA CARBOXYLASE AS ANAPLEROTIC ENZYMES IN SKELETAL-MUSCLE MITOCHONDRIA
    DAVIS, EJ
    SPYDEVOLD, O
    BREMER, J
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1980, 110 (01): : 255 - 262
  • [6] The malic dehydrogenase of animal tissues.
    Green, DE
    [J]. BIOCHEMICAL JOURNAL, 1936, 30 : 2095 - 2110
  • [7] HARADA K, 1968, J BIOL CHEM, V243, P4123
  • [8] THE DISPOSITION OF CITRIC-ACID CYCLE INTERMEDIATES BY ISOLATED RAT-HEART MITOCHONDRIA
    HILTUNEN, JK
    DAVIS, EJ
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1981, 678 (01) : 115 - 121
  • [9] UTILIZATION OF LEUCINE BY WORKING RAT-HEART
    ICHIHARA, K
    NEELY, JR
    SIEHL, DL
    MORGAN, HE
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1980, 239 (06): : E430 - E436
  • [10] IMPAIRED CARDIAC WORK AND OXYGEN-UPTAKE AFTER REPERFUSION OF REGIONALLY ISCHEMIC MYOCARDIUM
    KANNENGIESSER, GJ
    OPIE, LH
    VANDERWERFF, TJ
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1979, 11 (02) : 197 - 207