Hypoxanthine, xanthine and uridine in body fluids, indicators of ATP depletion

Measurements of hyp, xan and urd in body fluids can provide evidence of energy, ATP, depletion in the body, in organs or in cells. Such information is clinically useful in the many diseases in which cellular energy supplies cannot be maintained like perinatal asphyxia, hydrocephalus and vascular insufficiency in brain, heart, limbs, kidneys or other organs. Similar HPLC methods using reversed-phase C18 columns and quantitation by UV absorption have been employed in a variety of centres to yield almost identical results. These have been assembled in this review to form a series of reference values. The current analytical problems are reviewed. Since concentrations of hyp and xan may alter independently situations are discussed in which separate measurements rather than their summed, total oxypurine concentrations are needed. The biochemistry and physiology underlying the use of such analyses is examined to guide sampling of the appropriate body fluid at a relevant time and to avoid oversimplified interpretation of results as well as unnecessary arguments. Specifically: (1) Intracellular concentrations of hyp and xan are inversely related to adenylate energy change and therefore to the energy currency of the cell ATP. Uridine in tissues is similarly 'controlled'. (2) There is extensive evidence that large increases in hyp, xan and urd in body fluids indicate ATP depletion. (3) Small changes in hyp probably reflect alterations of ATP turnover. (4) Xanthine arises mainly from guanine and can change independently of hyp. (5) Clinically useful information is obtainable from hyp and xan concentrations in CSF, amniotic fluid, urine and plasma. Extensive clinical correlations are reviewed. At present we are in a development phase for which HPLC is ideal but the most efficient way to perform and use such analyses in routine clinical practice remains to be established.