Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication

Abstract

As one of the bicyclic metabolic pathways of one-carbon metabolism, methionine metabolism is the pivot linking the folate cycle to the transsulfuration pathway. In addition to being a precursor for glutathione synthesis, and the principal methyl donor for nucleic acid, phospholipid, histone, biogenic amine, and protein methylation, methionine metabolites can participate in polyamine synthesis. Methionine metabolism disorder can aggravate the damage in the pathological state of a disease. In the occurrence and development of chronic liver diseases (CLDs), changes in various components involved in methionine metabolism can affect the pathological state through various mechanisms. A methionine-deficient diet is commonly used for building CLD models. The conversion of key enzymes of methionine metabolism methionine adenosyltransferase (MAT) 1 A and MAT2A/MAT2B is closely related to fibrosis and hepatocellular carcinoma. In vivo and in vitro experiments have shown that by intervening related enzymes or downstream metabolites to interfere with methionine metabolism, the liver injuries could be reduced. Recently, methionine supplementation has gradually attracted the attention of many clinical researchers. Most researchers agree that adequate methionine supplementation can help reduce liver damage. Retrospective analysis of recently conducted relevant studies is of profound significance. This paper reviews the latest achievements related to methionine metabolism and CLD, from molecular mechanisms to clinical research, and provides some insights into the future direction of basic and clinical research.

Plasma amino acid profiles in dogs with closed extrahepatic portosystemic shunts are only partially improved 3 months after successful gradual attenuation

“…34 In human medicine, controversy exist as to whether methionine supplementation is useful in patients with chronic liver disease. 35 Our findings suggest that the liver-supportive diet used might not be ideally balanced in terms of amino acids for dogs with portosystemic shunting. A double-blind cross-over study found that clinical signs of HE significantly improved in dogs with PSS that received a diet based on soy instead of meat protein.…”

“…A double-blind cross-over study found that clinical signs of HE significantly improved in dogs with PSS that received a diet based on soy instead of meat protein. 35 Yet, the BCAA-to-AAA ratio of the soy-based diet was only 2.05 compared to 2.30 for the meat-based diet. Despite a lower BCAA-to-AAA ratio in the food, improved HE scores in that study were attributed to the fact that vegetable proteins are highly digestible leading to a higher absorption of amino acids in the small intestine and subsequently less nitrogen reaching the colon.…”

Deuterium Metabolic Imaging—Rediscovery of a Spectroscopic Tool

“…[methyl- 2 H 3 ] methionine : Methionine is an essential amino acid that has an important role in many cellular functions. In addition to being an essential component in the initiation of protein synthesis, methionine can also take part in (1) the methionine cycle, converted to the important methyl donor s-adenosylmethionine (SAM), (2) polyamine synthesis, (3) folate metabolism, and (4) glutathione synthesis via the trans-sulfuration pathway [ 127 , 128 ]. London et al administered L-[methyl- 2 H 3 ] methionine in excess to rodents in order to investigate its hepatic metabolism in particular its conversion to [methyl- 2 H 3 ] sarcosine, clearance of L-[methyl- 2 H 3 ] methionine, formation of N-trimethyl-labeled metabolites, and enrichment of water with deuterium [ 129 ].…”

Dithiothreitol causes toxicity in C. elegans by modulating the methionine-homocysteine cycle

“…Methionine metabolism and methyltransferases have important roles in regulating health and lifespan 39 , and defects in the methionine-homocysteine cycle have been linked with a large number of pathological conditions [40][41][42] . Therefore, the methionine-homocysteine cycle has become an important intervention point for improving lifespan and health 39,[42][43][44][45] .…”