K. Adachi et al., STUDIES ON UREA SYNTHESIS IN THE LIVER OF RATS TREATED CHRONICALLY WITH ETHANOL USING PERFUSED LIVERS, ISOLATED HEPATOCYTES, AND MITOCHONDRIA, Biochemical pharmacology, 50(9), 1995, pp. 1391-1399
Changes in urea synthesis in the liver of rats treated with 32% ethano
l in the drinking water for up to 6 months were studied using perfused
livers, isolated hepatocytes, and mitochondria. Results obtained from
ethanol-treated rats are summarized as follows: (1) the mitochondria
of the hepatocytes of rats treated with ethanol for 2 months or longer
became enlarged to various degrees, (2) the levels of ammonia in the
serum remained within a normal range, while those in liver tissue were
elevated compared with the control, (3) urea synthesis from ammonia i
n perfused livers was decreased markedly, while that from citrulline r
emained in the normal range, (4) the activities of carbamyl phosphate
synthetase (CPS; EC 2.7.2.5) and omithine transcarbamylase (OTC; EC 2.
1.3.3) in mitochondria were unchanged compared with those of the contr
ol, and (5) the levels of ATP in liver tissue and the ability of mitoc
hondria to synthesize ATP were decreased markedly compared with the co
ntrol. Both the level of ATP in the hepatocytes and the synthesis of u
rea from ammonia by perfused livers of rats treated with ethanol were
resistant to externally added ethanol, while those of control animals
were severely affected. These results suggest that the intracellular l
evel of ATP is intimately related to urea synthesis in both control an
d ethanol-treated animals, and lowered levels of ATP may be a key fact
or in the suppression of urea synthesis in ethanol-treated animals.