Newswise — Articles Appearing in JBC Online February 22, 2008 (Vol. 283, No. 9)

Sodium, Calcium, Potassium and Skin Color

Skin color is one of the most visible indicators that helps distinguish human appearance, and a new study provides more detail as to how one protein helps produce this wide palette.

In 2005 researchers identified a gene called SLC24A5 as a key determinant of skin color. Rebecca Ginger and colleagues now confirm that the protein product of this gene (NCKX5) is an ion exchanger; it exchanges sodium for calcium across a membrane, regulated by potassium. But unlike other NCKX proteins, they found that NCKX5 is not present on the cell surface, but internally in a compartment known as the trans-Golgi network. This compartment is where new proteins and vesicles are processed, modified and sorted.

When the researchers knocked out NCKX5 in melanocytes (the skin cells that manufacture the melanin pigment), melanin production decreased dramatically. They also demonstrated that changing the ancestral amino acid (alanine) at position 111 to the European form associated with lighter skintone (threonine) reduced NCKX5's exchanger activity.

While they plan on teasing out the exact biological mechanism, Ginger and colleagues propose that NCKX5 could play a direct role in the trafficking decisions that influence the assembly of melanosomes, the specialized cell vesicles where melanin is produced. Alterations that increase or decrease NCKX5 effectiveness would be expected to influence total skin pigment production.

Corresponding Authors: Rebecca Ginger and Martin Green, Unilever Corporate Research, Bedfordshire, UK

-------------------------How Embryonic Livers Store Energy

Researchers have uncovered how embryonic livers accumulate an important energy molecule even though they lacks the key enzyme responsible.

In adults, the liver stores glycogen, a sugar polymer that provides a steady supply of blood glucose when needed (e.g. during fasting). Glycogen production is controlled by an enzyme called glucokinase (GK), and mutations resulting in too much or too little GK will lead to hypo- and hyper-glycemia, respectively.

One interesting biological mystery has been that embryonic livers can store plenty of glycogen, yet they don't produce any GK; the liver only starts making this enzyme after newborns drink their first carbohydrate-rich milk.

Joan Guinovart and colleagues found that embryonic mouse livers circumvent the lack of GK by greatly overproducing (~200 fold higher than adult liver) another enzyme known as hexokinase (HK). Such as high amount is necessary because while HK can make glycogen, it's really inefficient.

However, unlike GK, HK makes glycogen independent of blood-glucose levels, and the researchers confirmed this by fasting pregnant mice and observing the embryonic livers did not alter their glycogen accumulation.

Thus, by using HK, embryos safeguard their glycogen production from any changes in maternal diet to ensure abundant storage. This is critical since glycogen is a newborn's principal source of energy in the critical time between birth and first milk meal.

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force. For more information about ASBMB, see the Society's Web site at

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