Review Article

Homocysteine as a Risk Factor for Atherosclerosis: Is Its Conversion to S-Adenosyl-L-Homocysteine the Key to Deregulated Lipid Metabolism?

Figure 2

A model of activation of UPR and upregulation of fatty acid, TAG, and sterol biosynthesis in response to inhibition of phospholipid methylation in hyperhomocysteinemia. Elevated Hcy levels via AdoHcy accumulation and inhibition of phospholipid methylation lead to accumulation of saturated PC molecular species in ER membranes followed by ER stress, UPR activation, and upregulation of fatty acid, TAG, and sterol biosynthesis. The enzymes involved in yeast and mammalian metabolism are shown in grey circles (see Figure 1). PE: phosphatidylethanolamine; PC: phosphatidylcholine; PEMT: phosphatidylethanolamine N-methyltransferase in mammals; Cho2 and Opi3: phosphatidylethanolamine N-methyltransferases in yeast.
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