Sex differences in the human metabolome

Men and woman differ in many ways, and now a study shows the human sexes differ in over a hundred metabolites and metabolism-related genes.

An international team of researchers, including Karsten Suhre of Weill Cornell Medical College in Doha, investigated the concentration of 131 metabolites in blood samples from more than 3,300 individuals: 102 of the metabolites had gender specific differences.

Many of the observed differences were in levels of molecules that play key roles in a wide range of cellular activities, such as amino acids, sugars and phospholipids.

The researchers then performed a genome-wide association study to compare the entire genomes of 1,809 individuals from the original sample, and identified several sex-specific single nucleotide polymorphisms in the CPS1 gene.

CPS1 encodes an enzyme called carbamoyl-phosphate synthase 1, which is expressed in mitochondria and plays an important role in metabolizing proteins and nitrogen and catalyses an early step in the biochemical pathway that produces urea in the kidney.

The study suggests that these differences affect whole metabolic pathways rather than individual metabolites, and could help to explain the differences between men and women in their susceptibility to certain diseases, such as coronary heart disease, lung cancer and multiple sclerosis.

"It is hard to say how the observed sex-differences translate into differences in cellular activity," says Kirstin Mittelstrass, the lead author of the study, "because the number of studies of gender differences in metabolism is very limited and most findings require confirmation."

"Our goal now is to extend the metabolite panel to get an even better overview of the human metabolome," she adds. "It will also be necessary to extend the number of subjects in our study populations."

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