Proteomics reveal a concerted upregulation of methionine metabolic pathway enzymes, and downregulation of carbonic anhydrase-III, in betaine supplemented ethanol-fed rats

Abstract

We employed a proteomic profiling strategy to examine the effects of ethanol and betaine diet supplementation on major liver protein level changes. Male Wistar rats were fed control, ethanol or betaine supplemented diets for 4 weeks. Livers were removed and liver cytosolic proteins resolved by one-dimensional and two-dimensional separation techniques. Significant upregulation of betaine homocysteine methyltransferase-1, methionine adenosyl transferase-1, and glycine N-methyltransferase were the most visually prominent protein changes observed in livers of rats fed the betaine supplemented ethanol diet. We hypothesise that this concerted upregulation of these methionine metabolic pathway enzymes is the protective mechanism by which betaine restores a normal metabolic ratio of liver S-adenosylmethionine to S-adenosylhomocysteine. Ethanol also induced significant downregulation of carbonic anhydrase-III protein levels which was not restored by betaine supplementation. Carbonic anhydrase-III can function to resist oxidative stress, and we therefore hypothesise that carbonic anhydrase-III protein levels compromised by ethanol consumption, contribute to ethanol-induced redox stress.

Liver Proteome Changes Induced by a Short-Term High-Fat Sucrose Diet in Wistar Rats

“…Ca3 is considered as one of the proteins involved in oxidative stress response both in liver and skeletal muscle [20]. However, it has also been reported as the worst catalyst for CO 2 hydration as compared to other isozymes [22]. We found Ca3 to be differentially upregulated in rats fed the HFSD.…”

Analysis of the liver mitochondrial proteome in response to ethanol andS-adenosylmethionine treatments: novel molecular targets of disease and hepatoprotection

“…A SAM-dependent increase in CDH may have the desired consequence of increased betaine formation needed for remethylation of homocysteine to methionine, thereby blunting the toxicity of homocysteine to induce ER stress (25). Data from this study and others (30,54) show that SAM or betaine treatments have the ability to attenuate many of the damaging effects of ethanol on the liver through modulation of key enzymes involved in methionine metabolism.…”

“…Recent proteomic data show that a betaine-supplemented ethanol diet preserves functionality of several key cytosolic enzymes of methionine metabolism including betaine homocysteine methyltransferase (BHMT) and methionine adenosyltransferase (30). Data presented herein also shows ethanol-and SAM-dependent alterations in the levels of mitochondrial proteins interconnected with methionine metabolism via choline and glycine metabolism; CDH, DMGDH, and SARDH.…”

“…D: relative abundances of those proteins (16 -24) present in the third lane (III), which corresponds to complex III and associated proteins. E shows the relative abundances of those proteins (25)(26)(27)(28)(29)(30)(31)(32)(33) present in the fourth lane (IV), which corresponds to complex IV and associated proteins. Numbers listed under each correspond to circled proteins located on the master map (A) and in Table 4.…”

PCMT1 gene polymorphisms, maternal folate metabolism, and neural tube defects: a case–control study in a population with relatively low folate intake

“…Adenosylhomocysteinase converts SAH to Hcy, which is re-methylated by 5-methyltetrahydrofolate back to methionine. It is reported that changes in the SAM/SAH ratio affected liver PIMT activity in rats after betaine administration (Kharbanda et al 2007(Kharbanda et al , 2009Ghandour et al 2002;Carter and Aswad 2008). Moreover, SAH is a potent inhibitor of many methyltransferases including PIMT.…”