October 2012

Taking serine metabolism seriously

Cover of the June 8, 2012, edition of The Journal of Biological Chemistry

Do you think serine metabolism is important? If you study the brain, development or epigenetics, it may be of value to you. Serine is involved in all of these processes in addition to many others.

In a recent Journal of Biological Chemistry minireview, Satish C. Kalhan of the Cleveland Clinic Lerner College of Medicine and Richard W. Hanson of the Case Western Reserve University School of Medicine argue that serine is underappreciated, and the authors make quite a case for it, underscoring the significance of serine metabolism.

The minireview, “Resurgence of serine: an often neglected but indispensable amino acid,” explains that the importance of serine is being realized as researchers learn more about its involvement in methyl group transfer, a process that occurs on DNA, RNA and protein and modifies a variety of processes in the cell. Specifically, serine contributes to the formation of S-adenosylmethionine, the methyl donor.

Because methylation regulates a wide range of events – from cell proliferation to gene expression – and is dependent upon serine, a proper understanding of this amino acid’s metabolism is critical.

Recent studies have shown that dietary serine is insufficient for the requirements of the cell. In fact, de novo synthesis predominates as the body’s source of serine. During gluconeogenesis, pyruvate is transformed into 3-phosphoglycerate. This intermediate is directed toward serine synthesis by 3-phosphoglycerate dehydrogenase, or 3-PGDH, which converts 3-phosphoglycerate to 3-phosphohydroxypyruvate, the serine precursor. This pathway, termed “serinoneogenesis,” was first described by Sean Brosnan and colleagues in their classic studies of serine metabolism.

The JBC minireview also covers recent studies on the alteration of serine metabolism. During dietary protein restriction, it was found that de novo synthesis increased. Serine synthesis normally occurs at the kidney, but under these conditions it also takes place at the liver.

The authors also review alterations to serine metabolism in cancer. Serine levels are high in some cancer cells due to the overexpression of 3-PGDH. The details are still unclear, but it likely contributes to the methylation that is needed for cell proliferation.

We have learned that serine is involved in more mechanisms than initially realized. Due to serine’s far-ranging effects in organisms, it is beneficial for scientists to be aware of its role in their research.


Photo of Elizabeth SandquistElizabeth Sandquist (elizabeth.overmoe@med.und.edu) is a graduate student at the University of North Dakota pursuing a Ph.D. in biochemistry and molecular biology. Follow her on Twitter at www.twitter.com/ilovebraaains.

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