Biochemistry

The field of biochemistry covers all of the individual jobs that cells must do to keep the body functioning. This includes turning food into fuel, and using the fuel for whatever is needed.

The hprt gene directs the production of a protein known as HPRT. Studies in biochemistry have shown that the job of HPRT is to recycle certain chemicals in the body known as purines. These purines are important for the life and operations of every cell in the body.

Purines

The purines are a group of molecules that are naturally found in all living things. They are involved in a great number of biochemical pathways that are essential for life. They provide the basic building blocks for DNA and RNA. ATP is a purine that serves as the currency of the majority of energy-requiring reactions in cells. The cyclic nucleotides and other purines such as adenosine serve as messenger molecules for cellular communication.

Because of the importance of purines for so many basic biological processes, their amounts are very tightly regulated. Cellular purines derive from two major sources. They can be made from other molecules in series of steps known as the de novo synthetic pathway, or they can be regenerated from bases hypoxanthine and guanine. This last pathway, recycling of hypoxanthine and guanine, is the reaction mediated by HPRT.

HPRT

HPRT is the abbreviation for a protein called hypoxanthine-guanine phosphoribosyltransferase. This protein is also called an enzyme, because it has a special function.

HPRT is found in virtually all cells from most living things including plants, animals, and even some microorganisms. It catalyzes the transfer of the 5-phosphoribosyl group from phosphoribosyl-pyrophosphate to the 9 position of the hypoxanthine or guanine base in the presence of magnesium to form the respective nucleotide and pyrophosphate (see figures).

In humans, the enzyme functions as a combination of four identical subunits, and the configuration of the active site has been studied in detail.

Uric acid

Uric acid is a chemical that is produced by the body as the final product of purine metabolism. Its chemical structure is shown in Figure 1. Everyone makes small amounts of uric acid, but people with Lesch-Nyhan disease make too much.

Figure 2 shows uric acid levels found in the blood. Normal people have levels that fall in the blue zone. In general, children have lower levels than adults, so the blue zone changes with age. The yellow circles show serum uric acid levels in individuals with Lesch-Nyhan disease. Most of these are outside of the normal range, though some are only a little bit high.

Most of the uric acid in the blood is filtered through the kidneys and then dumped into the urine. As a result, urine uric acid levels are also high in people with Lesch-Nyhan disease. Figure 3 shows uric acid levels in the urine. Normal people have levels that fall in the gray zone. The yellow circles show urine uric acid levels in individuals with Lesch-Nyhan disease, and most of these are again outside the normal range.