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Updated: Aug 10, 2026
14:27
Steady-state, Pre-steady-state, and Single-turnover Kinetic Measurement for DNA Glycosylase Activity
Published on: August 19, 2013
Substrate stabilization: genetically controlled reciprocal relationship of two human enzymes
Science (New York, N.Y.)
|February 6, 1970
Summary
5-Phosphoribosyl-1-pyrophosphate accumulates in individuals lacking hypoxanthine-guanine phosphoribosyltransferase. This substrate stabilizes adenine phosphoribosyltransferase, potentially explaining increased enzyme activity in these individuals.
Area of Science:
- Biochemistry
- Enzymology
- Human Physiology
Background:
- 5-Phosphoribosyl-1-pyrophosphate (PRPP) is a key intermediate in purine biosynthesis.
- Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are enzymes that utilize PRPP.
- Deficiency in HGPRT leads to Lesch-Nyhan syndrome, characterized by neurological and developmental abnormalities.
Purpose of the Study:
- To investigate the accumulation of PRPP in erythrocytes lacking HGPRT.
- To determine the effect of PRPP on the stability and activity of APRT.
- To elucidate the potential mechanism behind increased APRT activity in HGPRT-deficient individuals.
Main Methods:
- Analysis of PRPP levels in human erythrocytes from healthy individuals and those with HGPRT deficiency.
- In vitro experiments measuring the heat inactivation of purified APRT with and without PRPP.
- Assessing APRT activity in erythrocyte lysates from HGPRT-deficient patients.
Main Results:
- PRPP accumulates significantly in human erythrocytes lacking HGPRT.
- PRPP stabilizes purified APRT against thermal denaturation.
- APRT exhibits increased activity in erythrocytes deficient in HGPRT.
Conclusions:
- The accumulation of PRPP in HGPRT-deficient erythrocytes may serve a protective role by stabilizing APRT.
- Substrate-induced stabilization of APRT in vivo could account for the observed increase in its activity.
- This finding sheds light on the metabolic consequences of HGPRT deficiency and potential compensatory mechanisms.
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