Adaptation of hepatic enzyme activities to methionine excess

Abstract

Summary. Two groups of adult male rats 8 weeks old were fed a 10 p. 100 protein (casein) diet with or without 2 p. 100 methionine. After 8 rats in each group were killed at 10 a.m. on experimental days 1, 2, 4, 8 and 21, we studied the profiles of plasma non-esterified fatty acids (NEFA) and of the hepatic activities of pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), acetyl-CoA-carboxylase (Ac.CoA carbox), alanine aminotransferase (AAT), 3-phosphoglycerate dehydrogenase (3PGDH), serine dehydratase (Ser DH), ATP-methionine adenosyltransferase (MAd T), cystathionine synthase (Cysta S) and cystathionase (Cysta t).Animal food intake and body weight dropped on the first two days of methionine excess ; from day 8, they reached a new equilibrium which was much lower than that of the control animals.Hepatic enzyme adaptation could be the result of two mechanisms : (i) a short-term, mainly catabolic, process on the first 4 days of excess during which phosphoenolpyruvate carboxykinase activity and the plasma NEFA level were high, whilg glucose-6-phosphate dehydrogenase and malic enzyme activities were declining ; (ii) a later phenomenon, occurring on experimental day 8 and during which the activity of pyruvate kinase decreased slightly and that of malic enzyme and of 3-phosphoglycerate dehydrogenase declined sharply, while alanine aminotransferase activity was enhanced. The transsulfuration pathway specifically responded to methionine excess : ATP-methionine adenosyltransferase induction was immediate and depended on the amount of methionine ingested while cystathionine synthase did not seem to be closely regulated by methionine intake and cystathionase was only induced after 4 days. Each induction or repression has been discussed and related to the overall metabolic effects of the methionine excess reported in our previous papers.Introduction.

Effect of Excess Dietary Methionine on Weight Gain and Plasma Amino Acids in Kittens

“…Harper, Becker and Stucki (16) suggested that the more protein an animal (rat) eats, the easier the adaptation to an amino acid excess, a direct result of higher activity of the catabolic path ways. This may not be true for the kitten, since the hepatic enzymes involved in the catabolism of Met showed activities much lower than those of rats (6,17), and the adaptation was much slower in our experiment with kittens fed an 18% casein diet than for rats fed a 12% casein diet under similar conditions. Young rats fed a 2% Met diet needed 8 d to adapt and gain weight linearly (1.8 g/d versus 3.3 g for control rats), while the same phenomenon took place in 14-21 d in the grow ing kittens (15 g/d compared with 28 g in control kit tens).…”

“…The subse quent return of cystathionine concentration to normal levels may indicate that there was a delay in the in duction of cystathionase. An increase in activity oc curred faster (8 d) in rats receiving the same level of dietary Met (6). An increase in plasma neutral amino acids, alanine, proline, threonine, serine and asparagine, was found in blood samples taken on d 10 and 42.…”

“…Methionine (Met) has been shown to be one of the most toxic amino acids when given in amounts that substantially exceed the requirement for growth in rats (1,2), chicks (3), guinea pigs (4) or pigs (5). Previous experiments (6) have shown that growing rats fed a diet containing 2% excess Met needed 8 d to adapt to the new dietary conditions and stabilize their metabolism and weight gain.…”

Effects of methionine and related compounds on plasma cholesterol level in rats fed a high cholesterol diet.

“…2, methionine is known to be metabolized by two metabolic pathways, i.e., transsulfuration and transamination pathways (11,12). However, the relative contribution of each pathway , especially of the transamination path way, to the methionine metabolism remains unclear (22,23). It is of interest to know which pathway is responsible for the effect of methionine on plasma cholesterol level since the effect can be considered to be associated with the metabolism of methionine.…”

Content of Sulfur Amino Acids and Vitamin B₆ and Related Enzyme Activities in Rats with Chronic Renal Failure Fed a High Methionine Diet

“…Bocock et al [17] and Fau et al [18] reported that the activity of methionine adenosyltransferase in the liver of rats with 5/6 nephrectomy increased, and that methionine intake increased methionine adenosyltrans ferase activity. It was suggested that the cause of abnormal metabolim of sulfur-containing amino acids in patients with chronic renal failure was the decreased renal elimi nation, low activities of related enzymes and coenzyme, the low level of vitamin B(,.…”