Sleboda J, Pourfarzam M, Bartlett K, Osmundsen H
Department of Physiology and Biochemistry, University of Oslo, Norway.
Biochim Biophys Acta. 1995 Oct 5;1258(3):309-18. doi: 10.1016/0005-2760(95)00138-3.
(1) During peroxisomal beta-oxidation of [U-14C]hexadecanoate, at concentrations higher than 100 microM, long-chain 3-oxoacyl-CoA-esters and 3-oxobutyryl-CoA accumulate. Only 3-oxobutyryl-CoA accumulates at a low concentration of [U-14C]hexadecanoate. Accumulation of long chain 3-oxoacyl-CoA esters is most extensive when the supply of CoA can be considered limiting for beta-oxidation. (2) Added acetyl-CoA was found to inhibit peroxisomal beta-oxidation. This inhibition was not significantly relieved by added L-carnitine and carnitine acetyltransferase (EC 2.3.17). (3) Added L-carnitine, at concentrations below 0.2 mM, was found to stimulate peroxisomal beta-oxidation of [U-14C]hexadecanoate by up to 20%, causing the conversion of acetyl-CoA into acetylcarnitine. Higher concentrations of L-carnitine were progressively inhibitory to beta-oxidation. This effect was specific for L-carnitine as both D-carnitine and aminocarnitine neither caused stimulation at low concentrations, nor inhibition at higher concentrations. Added L-carnitine caused accumulation of acylcarnitines of chain-lengths ranging from 4 to 16 carbon-atoms. The inhibition observed with higher concentrations of added L-carnitine is likely due to conversion of [U-14C]hexadecanoate into [U-14C]hexadecanoylcarnitine. (4) Low concentrations of added hexadecanoylcarnitine was shown to inhibit peroxisomal beta-oxidation by about 15%, while added acetylcarnitine did not inhibit at concentrations up to 100 microM. (5) These data are interpreted to indicate significant control being exerted on flux at the stage of thiolysis either directly by means of CoA availability, or indirectly by means of the rate of acetyl-CoA generation.
(1) 在[U-14C]十六烷酸的过氧化物酶体β氧化过程中，当浓度高于100微摩尔时，长链3-氧代酰基辅酶A酯和3-氧代丁酰辅酶A会积累。在[U-14C]十六烷酸浓度较低时，只有3-氧代丁酰辅酶A会积累。当辅酶A的供应被认为是β氧化的限制因素时，长链3-氧代酰基辅酶A酯的积累最为广泛。(2) 发现添加的乙酰辅酶A会抑制过氧化物酶体β氧化。添加L-肉碱和肉碱乙酰转移酶（EC 2.3.17）并不能显著缓解这种抑制作用。(3) 发现添加浓度低于0.2毫摩尔的L-肉碱可使[U-14C]十六烷酸的过氧化物酶体β氧化最多提高20%，导致乙酰辅酶A转化为乙酰肉碱。较高浓度的L-肉碱对β氧化逐渐产生抑制作用。这种作用对L-肉碱具有特异性，因为D-肉碱和氨基肉碱在低浓度时既不会引起刺激，在高浓度时也不会引起抑制。添加L-肉碱会导致链长为4至16个碳原子的酰基肉碱积累。高浓度添加L-肉碱时观察到的抑制作用可能是由于[U-14C]十六烷酸转化为[U-14C]十六烷酰肉碱。(4) 低浓度添加的十六烷酰肉碱可使过氧化物酶体β氧化受到约15%的抑制，而添加的乙酰肉碱在浓度高达100微摩尔时不会产生抑制作用。(5) 这些数据被解释为表明在硫解阶段，通量受到显著控制，要么直接通过辅酶A的可用性，要么间接通过乙酰辅酶A的生成速率。
