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An orphan enzyme’s purpose

Oct. 4, 2012, 7:00 AM

(Wellcome Images)

The human cytochrome P450 enzymes are responsible for metabolizing a variety of substances – from lipids (fats) and steroid hormones to drugs and toxic chemicals. Fifty-seven P450 genes have been identified in the human genome, but 13 of those are termed “orphans” as their physiological functions are unknown.

F. Peter Guengerich, Ph.D., Harry Pearson Broquist Professor of Biochemistry, and graduate student Yi Xiao set out to determine the function of one such orphan, called P450 2W1, which is found at low levels in normal tissues but is highly expressed in colorectal tumors. The researchers incubated purified P450 2W1 with colorectal cancer extract to identify the enzyme’s substrates (the biological substances the enzyme acts on).

In the August Journal of Lipid Research, they report that the enzyme acts on a series of fatty acids and lysophospholipids. One of these lysophospholipids, lysophosphatidic acid, reportedly contributes to tumor initiation and progression. The findings suggest that up-regulated expression of P450 2W1 in colorectal tumors may be responsible for events contributing to tumor growth.

The research was supported by grants from the National Cancer Institute (CA090426) and the National Institute of Environmental Health Sciences (ES000267) of the National Institutes of Health.

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