The effect of tumour growth on liver pantothenate, CoA, and fatty acid synthetase activity in the mouse.

The effect of tumour growth on liver pantothenate, CoA, and fatty acid synthetase activity in the mouse.
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DOI:
10.1038/bjc.1988.14
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发表时间:
1988-01
影响因子:
8.8
通讯作者:
Campbell, E H
Campbell, E H
中科院分区:
医学1区
文献类型:
--
作者:
McAllister, R A;Fixter, L M;Campbell, E H

文献摘要

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采用酶法和微生物学方法测定荷瘤小鼠肝脏中辅酶A、乙酰辅酶A、脂肪酸合成酶活性和泛酸的含量。在携带TLX-5淋巴瘤、肉瘤180或纤维肉瘤的小鼠中发现CoA和乙酰CoA显著降低。这些变化伴随着显着减少泛酸和增加4-磷酸泛酸表明泛酸激酶活性的增加,由于辅酶A抑制酶的减少。相比之下,在携带TLX-5淋巴瘤的小鼠中,i. p.或s.c.这些变化可能是由于CoA途径中中间体转化率的大幅降低,或由于CoA或脂肪酸合成酶中磷酸泛酰巯基乙胺残基的降解而增加泛酸或4-磷酸泛酸的产生。携带这种肿瘤的小鼠肝脏中脂肪酸合成酶的活性显示出明显的降低,但不足以解释泛酸的增加,并且可能反映了将载脂蛋白转化为全酶所需的胞质CoA的减少。
Enzymatic, and microbiological assays were used to determine the hepatic contents of coenzyme A, acetyl CoA, fatty acid synthetase activity, and pantothenate in livers of tumour-bearing mice. Significant decreases in CoA and acetyl CoA were found in mice bearing TLX-5 lymphoma, sarcoma 180 or a fibrosarcoma. These changes were accompanied by significant decreases in pantothenate and increases in 4-phosphopantothenate suggesting an increase in pantothenate kinase activity due to reduction of CoA inhibition of the enzyme. In contrast, large increases were found in pantothenate and 4-phosphopantothenate in mice bearing TLX-5 lymphoma, i.p. or s.c. These changes could be due to a large reduction in the rate of conversion of an intermediate in the pathway of CoA, or increased production of pantothenate or 4-phosphopantothenate from the degradation of CoA or the phosphopantetheine residue in fatty acid synthetase. Activities of fatty acid synthetase in liver of mice bearing this tumour showed marked decreases, but were insufficient to account for the increase in pantothenate, and may reflect a reduction in cytosolic CoA needed for the conversion of the apo to the holoenzyme.