REGULATION OF BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE KINASE
REGULATION OF BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE KINASE
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DOI：
10.1016/0003-9861(84)90361-8
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发表时间：
1984-01-01
影响因子：
3.9
通讯作者：
HARRIS, RA
中科院分区：
文献类型：
--
作者：
PAXTON, R;HARRIS, RA
α-酮基异戊酸酯、α-酮基-β-甲基戊酸酯、α-酮基异戊酸酯、α-酮基戊酸酯、α-酮戊酸酯、α-酮戊酸酯和α-氯异戊酸酯对兔肝支链α-酮酸脱氢酶的抑制作用分别为0.065、0.49、2.5、0.2、0.5和0.08 mM。α-酮基异戊酸、α-酮-β-甲基戊酸和α-酮异戊酸激活大鼠心脏支链α-酮酸脱氢酶至总活性的50%所需的浓度(Mm)分别为0.07、0.10和0.25。辛酸(0.5)、乙酰乙酰-辅酶A(0.01)、甲基丙二酰辅酶A(0.2)、NADP+(1.5)和肝素(12微克/毫升)对分离的支链α-酮酸脱氢酶有抑制作用(140值，mm)。在ADP存在或不存在的情况下，该激酶活性被抑制.apprx。0.1mM异丁酰辅酶A、异戊酰辅酶A和丙二酰辅酶A，而不受NAD+和NADH(1 MM)、辅酶A、乙酰辅酶A、甲基巴豆酰辅酶A、β-羟基-β-甲基-戊二酰辅酶A、辛酰辅酶A、琥珀酰辅酶A和丙酰辅酶A(0.1 mM)的影响。以下化合物在2 mM时也不抑制支链α-酮酸脱氢酶激酶、乙酸酯、丙酸、β-羟丁酸酯、乳酸、乙酰乙酸酯、丙二酸酶、α-酮丙酸、琥珀酸、柠檬酸、草酰乙酸酯、FAD和NADPH。这些发现有助于解释Leu与Val和Ile相比对支链氨基酸代谢的独特影响，以及与丙酮酸脱氢酶和支链α-酮酸脱氢酶相关的酶的控制差异。
Isolated rabbit liver branched-chain .alpha.-ketoacid dehydrogenase was inhibited in a mixed manner relative to ATP by .alpha.-ketoisocaproate, .alpha.-keto-.beta.-methylvalerate, .alpha.-ketoisovalerate, .alpha.-ketocaproate, .alpha.-ketovalerate and .alpha.-chloroisocaproate with I40 values [amount of compound which produces 40% inhibition of enzyme activity], respectively, of 0.065, 0.49, 2.5, 0.2, 0.5 and 0.08 mM. The concentration (mM) of .alpha.-ketoisocaproate, .alpha.-keto-.beta.-methylvalerate and .alpha.-ketoisovalerate needed to activate branched-chain .alpha.-ketoacid dehydrogenase in the perfused rat heart to 50% of total activity was 0.07, 0.10 and 0.25, respectively. Isolated branched-chain .alpha.-ketoacid dehydrogenase kinase was inhibited (I40 values, mM) by octanoate (0.5), acetoacetyl-CoA (0.01), methymalonyl CoA (0.2), NADP+ (1.5) and heparin (12 .mu.g/ml). The kinase activity, in the presence or absence of ADP, was inhibited .apprx. 30% by 0.1 mM isobutyryl-CoA, isovaleryl-CoA and malonyl-CoA, while not affected by NAD+ and NADH (1 mM), CoA, acetyl-CoA methylcrotonyl-CoA, crotonyl-CoA, .beta.-hydroxy-.delta.-methyl-glutaryl-CoA, octanoyl-CoA, succinyl-CoA and propionyl-CoA (0.1 mM). The following compounds at 2 mM also did not inhibit branched-chain .alpha.-ketoacid dehydrogenase kinase; acetate, propionate, .beta.-hydroxybutyrate, lactate, acetoacetate, malonase, .alpha.-ketomalonate, succinate, citrate, oxaloacetate, FAD and NADPH. These findings help explain the unique effects of Leu compared with Val and Ile on branched-chain amino acid metabolsim and the differences between control of the kinases associated with pyruvate dehydrogenase and branched-chain .alpha.-ketoacid dehydrogenase.