This review summarizes currently available information about a crucial part of erythrocyte metabolism, that is, purine nucleotide conversions and their relationships with other conversion pathways. We describe the cellular resynthesis, interconversion, and degradation of purine compounds, and also the regulatory mechanisms in the conversion pathways. We also mention purine metabolism disorders and their clinical consequences. The literature is fragmentary because studies have concentrated only on selected aspects of purine metabolism; hence the need for a synthetic approach.

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The influence of short-term exposure to lead on the energetic status of erythrocytes in rats is reported in this study. The male Wistar rats selected for this study drank water containing 1% lead(II) acetate and/or intraperitoneal injections of 1 or 2 mg/kg body wt every 4 d starting on the eighth of the experiment, over a period of 1 mo. The whole-blood lead concentration measured after 4 wk was 1.51-35.31 microg/dL. The concentrations of adenosine, adenosine triphosphates, diphosphates, and monophosphates (ATP, ADP, and AMP), guanine triphosphates, diphosphates and monophosphates (GTP, GDP, and GMP), guanosine (Guo), inosine (Ino), inosine monophosphate (IMP), hypoxantine (Hyp), and nicotinamide dinucleotide and its phosphate (NAD(+) and NADP(+)) were determined by high-performance liquid chromatography (HPLC). The mean concentrations of ATP, GTP, NAD(+), and NADP(+) and those of adenylate (AEC) and guanylate (GEC) were significantly reduced in erythrocytes from the animals exposed to lead when compared to untreated controls. These results suggest that a lead ion disrupts the erythrocyte energy pathways. The decreases of NAD(+) and ATP could be used as an indicator of the extent of exposure to low levels of lead.

Multidrug resistance (MDR) of tumour cells is related to the overexpression of ATP-dependent pumps responsible for the active efflux of antitumour agents out of resistant cells. Benzoperimidine and anthrapyridone compounds exhibit comparable cytotoxic activity against sensitive and MDR tumour cells. They diffuse extremely rapidly across the plasma membrane and render the ATP-dependent efflux inefficient. Such uptake could disturb an energy metabolism of normal cells possessing an elevated level of ATP-dependent proteins, especially erythrocytes having a high level of the MRP1, MRP4 and MRP5 proteins. In this study the effect of five antitumour agents: benzoperimidine (BP1), anthrapyridones (CO1, CO7) and reference drugs used in the clinic: doxorubicin (DOX) and pirarubicin (PIRA), on the energetic state in human erythrocytes has been examined. These compounds have various types of structure and kinetics of cellular uptake (slow--DOX, CO7, moderate--PIRA, fast--BP1, CO1) resulting in their different ability to saturate ATP-dependent transporters. The energetic state of erythrocytes was examined by determination of purine nucleotide contents (ATP, ADP, AMP), NAD(+) and values of adenylate energy charge (AEC) using an HPLC method. It was found that the level of nucleotides as well as the AEC value of erythrocytes were not changed during 24 h of incubation with these agents independently of their structure and ability to saturate ATP-dependent pumps. This is a very promising result in view of their potential use in the clinic as antitumour drugs against multidrug resistant cancers.