Abstract
The sequence of the human genome together with sequence similarity analyses has advanced the discovery of missing steps in the mitochondrial one-carbon metabolism pathway. That together with the revived interest in cancer metabolism has brought the research on one-carbon metabolism back under the spotlight. Here, we present a brief review of recent advances in the field of one-carbon metabolism, with a bias towards its relevance to cell growth and proliferation in human cancers. We will address the requirements of one-carbon metabolism for biosynthesis and the major sources to satisfy that demand. We will also discuss some recent discoveries indicating a role of one-carbon metabolism beyond biosynthesis. We conclude with a concise enumeration of some fundamental questions that remain unanswered.
Highlights
The one-carbon metabolism pathway is composed of biochemical reactions that mediate the transfer of a one-carbon moiety from donor to acceptor molecules, using folate as a cofactor [1]
We summarize recent discoveries regarding the compartmentalization of mammalian one-carbon metabolism in the context of cancer
In cells transfected with isocitrate dehydrogenase 1 (IDH1) mutant enzyme, the 2HG M + 1 fraction serves as a readout of the Serine hydroxymethyltransferase (SHMT)/methylene-tetrahydrofolate cyclohydrolase (MTHFD) activity in the cytosol, and in cells transfected with isocitrate dehydrogenase 2 (IDH2) mutant enzyme, the 2HG M + 1 fraction serves as a readout of the SHMT/MTHFD activity in the mitochondria
Summary
Keywords cancer metabolism; cell growth; folate metabolism; mitochondria metabolism; one-carbon metabolism. The sequence of the human genome together with sequence similarity analyses has advanced the discovery of missing steps in the mitochondrial onecarbon metabolism pathway. That together with the revived interest in cancer metabolism has brought the research on one-carbon metabolism back under the spotlight. We present a brief review of recent advances in the field of one-carbon metabolism, with a bias towards its relevance to cell growth and proliferation in human cancers. We will address the requirements of one-carbon metabolism for biosynthesis and the major sources to satisfy that demand. We will discuss some recent discoveries indicating a role of one-carbon metabolism beyond biosynthesis. We conclude with a concise enumeration of some fundamental questions that remain unanswered
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