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Malate oxidase

In enzymology, a malate oxidase (EC 1.1.3.3) is an enzyme that catalyzes the chemical reaction

malate oxidase
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EC no.1.1.3.3
CAS no.9028-73-3
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(S)-malate + O2 oxaloacetate + H2O2

Thus, the two substrates of this enzyme are (S)-malate and O2, whereas its two products are oxaloacetate and H2O2.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with oxygen as acceptor. The systematic name of this enzyme class is (S)-malate:oxygen oxidoreductase. Other names in common use include FAD-dependent malate oxidase, malic oxidase, and malic dehydrogenase II. This enzyme participates in pyruvate metabolism. It employs one cofactor, FAD. The enzyme is commonly localized on the inner surface of the cytoplasmic membrane although another family member (malate dehydrogenase 2 (NAD)) is found in the mitochondrial matrix.

Mechanisms

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Malate oxidase belongs to the family of malate dehydrogenases (EC 1.1.1.37) (MDH) that reversibly catalyze the oxidation of malate to oxaloacetate by means of the reduction of a cofactor. The most common isozymes of malate dehydrogenase use NAD+ or NADP+ as a cofactor to accept electrons and protons.[1]

 
Reduction of Vitamin K by the addition of hydrogen to the quinone ring and reverse oxidation reaction with subsequent formation of H2O2 from oxygen

However, the main difference of malate oxidase is that it normally employs FAD as redox partner as alternative.[2][3][4] Contrary to pyridine based NAD+/NADP+, FAD comprises a quinone moiety, which is reduced by the forward reaction. FAD is thereby converted to FADH2. In this case, malate oxidase is qualified as malate dehydrogenase (quinone).

In mutant strains of Escherichia coli lacking the activity of NAD-dependent malate dehydrogenase, malate oxidase is expressed. It is suggested that products of malate dehydrogenase could be responsible for repression of malate oxidase.[5][6] This would confirm the existence of a family of structurally different malate dehydrogenases. Malate oxidase is induced only in cells, which completely lack the activity of NAD-specific malate dehydrogenase.[7][8]

Irradiation of cytoplasm membranes of Mycobacterium smegmatis with ultraviolet light (360 nm) for 10 minutes resulted in about a 50% loss of malate oxidase activity. The addition of vitamin K, containing a functional naphthoquinone ring, restores the oxidation activity of malate oxidase.[9] The quinone functionality of vitamin K can hence act as an alternative for FAD.[10]

Biological Reference

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However, instead of using NAD+, NADP+ or FAD as cofactors, malate oxidase can also shift to oxygen as oxidant and proton acceptor.[11]

(S)-malate + O2 ⇌ oxaloacetate + H2O2

 
Reversible reaction of (S)-malate to oxaloactetate with oxygen as the proton acceptor (oxidant), catalyzed by malate oxidase.

Although seemingly unlikely because of its reactive oxidative character, hydrogen peroxide is found in biological systems including the human body.[12] It signals oxidative stress from wounds to the immune system to recruit white blood cells for the healing process.

A study in Nature suggested that asthma sufferers have higher levels of hydrogen peroxide in their lungs than healthy people, which would explain why these patients also have inappropriate levels of white blood cells in their lungs.[13][14] Asthma sufferers might have certain variations in cellular levels of NAD+/NADP+ or FAD, which causes malate oxidase to shift to oxygen as its oxidant, due to its high abundancy in the lungs. This could be a possible explanation for the elevated levels of hydrogen peroxide in their lungs.

Uses

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Topical compositions of malate oxidase combined with suitable disease-detecting biomarkers and a chemiluminescent dye are used in disease detecting systems.[12] The biomarker activates the malate oxidase to generate hydrogen peroxide that excites the light-emitting dye, which exhibits chemiluminescence in the presence of the peroxide. Such contemporary compositions are thus used as a diagnostic tool for detecting diseases.

In a similar method, malate oxidase is used in the transcutaneous measurement of the amount of a substrate in blood.[15] The method is conducted by contacting the skin with the enzyme, reacting the substrate with the enzyme and directly detecting the amount of H2O2 produced as a measure of the amount of substrate in the blood, with use of a hydrogen peroxide electrode. Further dermatological applications are in drugs or cosmetic agents, comprising a suitable substrate and malate oxidase as hydrogen peroxide producing enzyme for skin lightening and age spots or freckles.[16][17]

Other illustrative uses that employ the capacity of malate oxidase to yield hydrogen peroxide in the presence of a suitable substrate, including malate, are found in toothpaste to remove bacterial plaque,[18] cleaning compositions for removing blood stains and the like,[19] and in the removal of chewing gum lumps stuck on surfaces by enzymatic degradation.[20]

Malate oxidase is also employed in the inhibition of corrosion by dissolved oxygen in water by converting it to hydrogen peroxide, which is subsequently broken down into water and oxygen by catalase.[21]

References

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  1. ^ McKeehan, W. L.; McKeehan, K. A. (1982-02-01). "Changes in NAD(P)+-dependent malic enzyme and malate dehydrogenase activities during fibroblast proliferation". Journal of Cellular Physiology. 110 (2): 142–148. doi:10.1002/jcp.1041100206. ISSN 0021-9541. PMID 7068771.
  2. ^ Hebeler, B. H.; Morse, S. A. (1976-10-01). "Physiology and metabolism of pathogenic neisseria: tricarboxylic acid cycle activity in Neisseria gonorrhoeae". Journal of Bacteriology. 128 (1): 192–201. doi:10.1128/JB.128.1.192-201.1976. ISSN 0021-9193. PMC 232843. PMID 824268.
  3. ^ Prasada Reddy, T. L.; Suryanarayana Murthy, P.; Venkitasubramanian, T. A. (1975-02-17). "Variations in the pathways of malate oxidation and phosphorylation in different species of Mycobacteria". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 376 (2): 210–218. doi:10.1016/0005-2728(75)90012-2. ISSN 0006-3002. PMID 234747.
  4. ^ Cohn, D. V. (1958-08-01). "The enzymatic formation of oxalacetic acid by nonpyridine nucleotide malic dehydrogenase of Micrococcus lysodeikticus". The Journal of Biological Chemistry. 233 (2): 299–304. ISSN 0021-9258. PMID 13563491.
  5. ^ Narindrasorasak, S.; Goldie, A. H.; Sanwal, B. D. (1979-03-10). "Characteristics and regulation of a phospholipid-activated malate oxidase from Escherichia coli". The Journal of Biological Chemistry. 254 (5): 1540–1545. ISSN 0021-9258. PMID 368072.
  6. ^ Kollöffel, C. (1970-12-01). "Oxidative and phosphorylative activity of mitochondria from pea cotyledons during maturation of the seed". Planta. 91 (4): 321–328. doi:10.1007/BF00387505. ISSN 0032-0935. PMID 24500096.
  7. ^ Goldie, A. H.; Narindrasorasak, S.; Sanwal, B. D. (1978-07-28). "An unusual type of regulation of malate oxidase synthesis in Escherichia coli". Biochemical and Biophysical Research Communications. 83 (2): 421–426. doi:10.1016/0006-291x(78)91007-0. ISSN 0006-291X. PMID 358983.
  8. ^ Sanwal, B. D. (1969-04-10). "Regulatory mechanisms involving nicotinamide adenine nucleotides as allosteric effectors. I. Control characteristics of malate dehydrogenase". The Journal of Biological Chemistry. 244 (7): 1831–1837. ISSN 0021-9258. PMID 4305466.
  9. ^ Prasada Reddy, T. L.; Suryanarayana Murthy, P.; Venkitasubramanian, T. A. (1975-09-01). "Respiratory chains of Mycobacterium smegmatis". Indian Journal of Biochemistry & Biophysics. 12 (3): 255–259. ISSN 0301-1208. PMID 1221028.
  10. ^ Benziman, M., Perez, L. (1965).”The participation of vitamin K in malate oxidation by Acetobacter xylinum”. Biochemical and Biophysical Research Communications, 19(1), 127-32.
  11. ^ EP application 0118750, Hopkins, Thomas R. “Regeneration of NAD(P) cofactor”, published 1984-09-19, assigned to Phillips Petroleum Co.
  12. ^ a b US application 2013/0022685 A1, Sample, Jennifer L. et al. “Topical compositions and methods of detection and treatment”, published 2013-01-24, assigned to The Johns Hopkins University.
  13. ^ "Natural bleach 'key to healing'". BBC News. 6 June 2009. Retrieved 8 March 2017.
  14. ^ Niethammer, Philipp; Grabher, Clemens; Look, A. Thomas; Mitchison, Timothy J. (2009-06-18). "A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish". Nature. 459 (7249): 996–999. doi:10.1038/nature08119. ISSN 1476-4687. PMC 2803098. PMID 19494811.
  15. ^ US patent 4,458,686, Clark, Leland C. “Cutaneous methods of measuring body substances”, issued 1984-07-10, assigned to Children’s Hospital Medical Center.
  16. ^ DE application 10 2009 045 798 A1, Janßen, Frank, et al. “Enzymatische Hautaufhellung”, published 2010-08-05, assigned to Henkel Ag & Co. KGaA.
  17. ^ JP application H07165553, Deguchi, Tetsuya, et al., “Agent for preventing and treating disease caused by melamin”, published 1995-06-27, assigned to Kobe Steel Ltd.
  18. ^ GB patent 1 309 282, “Enzymatic dentifrices”, published 1973-03-07, assigned to Telec S.A.
  19. ^ US application 2008/0051310 A1, De Dominicis, Mattia, et al. “Enzymes as active oxygen generators in cleaning compositions”, published 2008-02-28, assigned to Reckitt Benckiser N.V.
  20. ^ US application 2009/0203564 A1, Wittorff, Helle, et al. “Method of cleaning surface attached with at least one chewing gum lump”, published 2009-08-13.
  21. ^ US application 2008/0020439 A1, De Dominicis, Mattia, et al. “Enzymes as corrosion inhibitors by removal of oxygen dissolved in water”, published 2008-01-24, assigned to Reckitt Benckiser N.V.
  • COHN DV (1958). "The enzymatic formation of oxalacetic acid by nonpyridine nucleotide malic dehydrogenase of Micrococcus lysodeikticus". J. Biol. Chem. 233 (2): 299–304. PMID 13563491.
  • Narindrasorasak S, Goldie AH, Sanwal BD (1979). "Characteristics and regulation of a phospholipid-activated malate oxidase from Escherichia coli". J. Biol. Chem. 254 (5): 1540–5. PMID 368072.
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