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Evidence of a new phosphoryl transfer system in nucleotide metabolism.
FEBS J. 2009 Jan; 276(1):271-85
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02 Jan 2009
Barry Stoddard
F1000 Chemical Biology
Arnold Digital Library, Fred Hutchinson Cancer Research Center,
USA.
F1000 Chemical Biology
Arnold Digital Library, Fred Hutchinson Cancer Research Center,
USA.
Interesting Hypothesis, New Finding
DOI: 10.3410/f.1139021.596126
This paper presents evidence that the directly coupled activity of three enzymes (adenylate kinase, adenosine kinase and adenosine deaminase) can catalyze the formation of ADP directly from two molecules of AMP -- providing a route to ADP formation under metabolic conditions where ATP levels are depleted.
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This paper presents evidence that the directly coupled activity of three enzymes (adenylate kinase, adenosine kinase and adenosine deaminase) can catalyze the formation of ADP directly from two molecules of AMP -- providing a route to ADP formation under metabolic conditions where ATP levels are depleted.
This finding, aside from hypothesizing a novel route to ADP formation using only low energy precursors, may have medical importance, as ATP depletion (and AMP accumulation) is known to occur under a variety of hypoxic or anoxic conditions (for example, during advanced tumorigenesis).
This study may add detail to our growing understanding of the metabolism of tumor beds, which is heavily reliant upon glycolysis and fermentation and displays a significant shift in the expression levels and isozyme composition of many of the enzymes involved in those processes.
This finding, aside from hypothesizing a novel route to ADP formation using only low energy precursors, may have medical importance, as ATP depletion (and AMP accumulation) is known to occur under a variety of hypoxic or anoxic conditions (for example, during advanced tumorigenesis).
This study may add detail to our growing understanding of the metabolism of tumor beds, which is heavily reliant upon glycolysis and fermentation and displays a significant shift in the expression levels and isozyme composition of many of the enzymes involved in those processes.
Disclosures
None declared
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Stoddard B: F1000Prime Recommendation of [Vannoni D et al., FEBS J 2009, 276(1):271-85]. In F1000Prime, 02 Jan 2009; DOI: 10.3410/f.1139021.596126. F1000Prime.com/1139021#eval596126
F1000Prime Recommendations, Dissents and Comments for [Vannoni D et al., FEBS J 2009, 276(1):271-85]. In F1000Prime, 25 May 2013; F1000Prime.com/1139021
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Crude rat liver extract showed AMP-AMP phosphotransferase activity which, on purification, was ascribed to a novel interaction between adenylate kinase, also known as myokinase (EC 2.7.4.3), and adenosine kinase (EC 2.7.1.20). The activity was duplicated using the same enzymes purified from recombinant sources. The reaction requires physical contact between myokinase and adenosine kinase, and the net reaction is aided by the presence of adenosine deaminase (EC 3.5.4.4), which fills the gap in the energy balance of the phosphoryl transfer and shifts the equilibrium towards ADP and inosine synthesis. The proposed mechanism involves the association of adenosine kinase and myokinase through non-covalent, transient interactions that induce slight conformational changes in the active site of myokinase, bringing two already bound molecules of AMP together for phosphoryl transfer to form ADP. The proposed mechanism suggests a physiological role for the enzymes and for the AMP-AMP phosphotransferase reaction under conditions of extreme energy drain (such as hypoxia or temporary anoxia, as in cancer tissues) when the enzymes cannot display their conventional activity because of substrate deficiency.
DOI: 10.1111/j.1742-4658.2008.06779.x
PMID: 19049516
