Malonyl-CoA and the regulation of fatty acid oxidation in soleus muscle
Malonyl-CoA and the regulation of fatty acid oxidation in soleus muscle
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DOI：
10.1042/bj3340233
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发表时间：
1998-08-15
影响因子：
4.1
通讯作者：
Saggerson, ED
中科院分区：
文献类型：
--
作者：
Alam, N;Saggerson, ED
1.将大鼠比目鱼肌条与5 mM葡萄糖孵育，测定组织代谢物。或者，将肌条与5 mM葡萄糖和0.2 mM棕榈酸酯孵育，并测量外源棕榈酸酯或预先标记的甘油脂释放的脂肪酸形成(CO2)-C-14的情况。依托莫昔尔抑制线粒体显性形式的肉碱棕榈酰基转移酶(CPT1)，增加组织中长链脂肪酰辅酶A酯的含量，降低脂肪酰基肉碱/脂肪酰辅酶A的比率，提示这种变化可能是CPT1.3抑制的诊断依据。在一系列孵育条件下，组织中丙二酰辅酶A和长链脂肪酰辅酶A酯的含量呈正相关。在这两种代谢物含量增加的情况下(即在胰岛素或3 mM二氯乙酸酯的情况下)，脂肪酰基肉碱与脂肪酰辅酶A的比率相应降低，β-氧化减少。异丙肾上腺素或棕榈酸酯(0.5 mM)拮抗胰岛素的作用，降低丙二酰辅酶A和长链脂肪酰辅酶A的含量，增加脂肪酰卡尼汀与脂肪酰辅酶A的比值，增加β-氧化作用。这些发现与以下观点一致，即所有这些药物都可以导致I型骨骼肌中CPT1的急性调节。加入5-氨基-4-咪唑甲酰胺核糖核苷(AICAriboside)以激活AMP激活的蛋白激酶可降低组织中丙二酰辅酶A的含量。AICAriboside在肌条中也有抗脂作用。测定了比目鱼肌和具有代表性的IIa型和IIb型肌肉的ATP-柠檬酸裂解酶、乙酰辅酶A羧基酶、脂肪酸合成酶和丙二酰辅酶A脱羧酶的活性。丙二酰辅酶A脱羧酶的胞浆活性似乎为丙二酰辅酶A在骨骼肌中的处置提供了一条可行的途径。
1. Rat soleus strips were incubated with 5 mM glucose, after which tissue metabolites were measured. Alternatively, muscle strips were incubated with 5 mM glucose and 0.2 mM palmitate, and the formation of (CO2)-C-14 from exogenous palmitate or from fatty acids released from prelabelled glycerolipids was measured.2. Etomoxir, which inhibits the mitochondrial overt form of carnitine palmitoyltransferase (CPT1), increased the tissue content of long-chain fatty acyl-CoA esters and decreased the ratio of fatty acylcarnitine to fatty acyl-CoA, suggesting that such changes could be a diagnostic for the inhibition of CPT1.3. Over a range of incubation conditions there was a positive correlation between the tissue contents of malonyl-CoA and long-chain fatty acyl-CoA esters. Under conditions in which these two metabolites increased in content (i.e. with insulin or with 3 mM dichloroacetate) there was a corresponding decrease in the ratio of fatty acylcarnitine to fatty acyl-CoA and a decrease in beta-oxidation. Isoprenaline or palmitate (0.5 mM) opposed the effect of insulin, decreasing the contents of malonyl-CoA and long-chain fatty acyl-CoA, increasing the ratio of fatty acylcarnitine to fatty acyl-CoA and increasing beta-oxidation. These findings are consistent with the notion that all of these agents can cause the acute regulation of CPT1 in Type I skeletal muscle.4. The addition of 5-amino-4-imidazolecarboxamide ribonucleoside (AICAriboside) to cause activation of the AMP-activated protein kinase decreased the tissue content of malonyl-CoA. AICAriboside also had an antilipolytic effect in the muscle strips.5. Measurements were made of the activities of ATP-citrate lyase, acetyl-CoA carboxylase, fatty acid synthase and malonyl-CoA decarboxylase in soleus muscle and in representative Type IIa and Type IIb muscles. A cytosolic activity of malonyl-CoA decarboxylase would seem to offer a feasible route for the disposal of malonyl-CoA in skeletal muscle.