Zierz S, Engel A G
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Biochem J. 1987 Jul 1;245(1):205-9. doi: 10.1042/bj2450205.
The inhibition of carnitine palmitoyltransferase (CPT, EC 2.3.1.21) by malonyl-CoA, acetyl-CoA and free CoA was studied in sonicated skeletal-muscle homogenates from normal human subjects and from five patients with a mutant CPT [Zierz & Engel (1985) Eur. J. Biochem. 149, 207-214]. (1) Malonyl-CoA, acetyl-CoA and CoA were competitive inhibitors of CPT with palmitoyl-CoA. (2) Acetyl-CoA and CoA inhibited normal and mutant CPT to the same degree, whereas malonyl-CoA inhibited mutant CPT more than normal CPT. (3) Triton X-100 abolished the inhibition of normal CPT by malonyl-CoA, but not by acetyl-CoA or CoA. Triton X-100 by itself caused loss of activity of the mutant CPT. (4) In the concentration range 0.1-0.4 mM, the inhibitory effects of any two of the three inhibitors were synergistic. (5) The inhibitory constants (Ki) for acetyl-CoA and CoA were close to 45 microM. The Ki for malonyl-CoA was 200-fold lower, or 0.22 microM. Addition of 40 microM-acetyl-CoA or CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. Addition of 20 microM-CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. (6) The findings indicate that acetyl-CoA and CoA can inhibit CPT at the catalytic site or a nearby site which is different from that at which malonyl-CoA inhibits CPT. (7) The fact that small changes in the concentration of acetyl-CoA and CoA can antagonize the inhibitory effect of malonyl-CoA suggests that these compounds could modulate the inhibition of CPT by malonyl-CoA.
在来自正常人类受试者以及五名患有肉碱棕榈酰转移酶（CPT，EC 2.3.1.21）突变体的患者的超声处理的骨骼肌匀浆中，研究了丙二酰辅酶A、乙酰辅酶A和游离辅酶A对肉碱棕榈酰转移酶的抑制作用[齐尔兹和恩格尔（1985年），《欧洲生物化学杂志》149卷，207 - 214页]。（1）丙二酰辅酶A、乙酰辅酶A和辅酶A是肉碱棕榈酰转移酶与棕榈酰辅酶A的竞争性抑制剂。（2）乙酰辅酶A和辅酶A对正常和突变型肉碱棕榈酰转移酶的抑制程度相同，而丙二酰辅酶A对突变型肉碱棕榈酰转移酶的抑制作用比对正常肉碱棕榈酰转移酶的抑制作用更强。（3）曲拉通X - 100消除了丙二酰辅酶A对正常肉碱棕榈酰转移酶的抑制作用，但未消除乙酰辅酶A或辅酶A对其的抑制作用。曲拉通X - 100本身导致突变型肉碱棕榈酰转移酶活性丧失。（4）在0.1 - 0.4 mM的浓度范围内，三种抑制剂中任意两种的抑制作用具有协同性。（5）乙酰辅酶A和辅酶A的抑制常数（Ki）接近45 μM。丙二酰辅酶A的Ki低200倍，即0.22 μM。添加40 μM乙酰辅酶A或辅酶A导致乙酰辅酶A的Ki增加3倍。添加20 μM辅酶A导致乙酰辅酶A的Ki增加3倍。（6）研究结果表明，乙酰辅酶A和辅酶A可在催化位点或与丙二酰辅酶A抑制肉碱棕榈酰转移酶的位点不同的附近位点抑制肉碱棕榈酰转移酶。（7）乙酰辅酶A和辅酶A浓度的微小变化可拮抗丙二酰辅酶A的抑制作用这一事实表明，这些化合物可调节丙二酰辅酶A对肉碱棕榈酰转移酶的抑制作用。
