Table 1.

The main CLDs affected by methionine deficiency, and of any of the enzymes that participate in the transsulfuration pathway

Chronic liver disease	Adverse consequences of methionine deficiency	References
Viral hepatitis	Low STAT methylation level, the change of MAT1A/MAT2A and the lower deposition of H3K4me3 on HBV-DNA	31,57–59
Alcoholic liver disease	Cystathionine and serum homocysteine elevate. MATα1 level, GSH, folate and vitamin B6, and B12 decrease. Decreased ratio of SAM/SAH directly affects the methylation level, ethanol tampers with multiple enzymes, including MAT, BHMT, and various MTs. The lack of PRMT causes lower PE methylation, which leads to SAM accumulation and sensitivity to oxidative stress.	73,74,76–78,81–83
Nonalcoholic fatty liver disease	Hepatic Fgf21 mRNA was increased, which is a modulator of energy homeostasis. FFA accumulates and can cause lipotoxicity through JNK1 activation. CD36 level, the PC/PE ratio, and serum homocysteine increase.	93,96,98–100
Liver fibrosis and cirrhosis	The phosphorylation of MATα2 and MATβ proteins enhanced. The binding of E2F-4 to MAT2A promoter attenuates. SAM/SAH ratio and DNA methylation decrease.	22,113,117
Hepatocellular carcinoma	GNMT is downregulated, MAT1A expression decreases while MAT2A increases. The activity of ODC increases. High levels of CBS express in HCC, which involve in cell proliferation. The expression of SAHH/AHCY is inhibited.	48,109,131,138,152