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

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.