Malate oxidase

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malate oxidase
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EC no. 1.1.3.3
CAS no. 9028-73-3
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In enzymology, a malate oxidase (EC 1.1.3.3) is an enzyme that catalyzes the chemical reaction

Contents

(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

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 Vitamin K redox2.jpg
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

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. S(Malate)tooxaloacetate.jpg
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

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]

Related Research Articles

<span class="mw-page-title-main">Citric acid cycle</span> Chemical reactions to release energy in cells

The citric acid cycle —also known as the Krebs cycle, Szent-Györgyi-Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a 'cycle', it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.

A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as forward reactions, and in some cases this has physiological significance: for example, alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde in animals, but in yeast it catalyzes the production of ethanol from acetaldehyde.

<span class="mw-page-title-main">Glucose oxidase</span> Class of enzymes

The glucose oxidase enzyme also known as notatin is an oxidoreductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. This enzyme is produced by certain species of fungi and insects and displays antibacterial activity when oxygen and glucose are present.

<span class="mw-page-title-main">Nicotinamide adenine dinucleotide phosphate</span> Chemical compound

Nicotinamide adenine dinucleotide phosphate, abbreviated NADP+ or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form of NADP+, the oxidized form. NADP+ is used by all forms of cellular life.

<span class="mw-page-title-main">Oxaloacetic acid</span> Organic compound

Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes that occur in animals. It takes part in gluconeogenesis, the urea cycle, the glyoxylate cycle, amino acid synthesis, fatty acid synthesis and the citric acid cycle.

<span class="mw-page-title-main">Malate dehydrogenase</span> Class of enzymes

Malate dehydrogenase (EC 1.1.1.37) (MDH) is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate using the reduction of NAD+ to NADH. This reaction is part of many metabolic pathways, including the citric acid cycle. Other malate dehydrogenases, which have other EC numbers and catalyze other reactions oxidizing malate, have qualified names like malate dehydrogenase (NADP+).

<span class="mw-page-title-main">Isocitrate dehydrogenase</span> Class of enzymes

Isocitrate dehydrogenase (IDH) (EC 1.1.1.42) and (EC 1.1.1.41) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha-ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and use NADP+ as a cofactor instead of NAD+. They localize to the cytosol as well as the mitochondrion and peroxisome.

<span class="mw-page-title-main">Mitochondrial matrix</span> Space within the inner membrane of the mitochondrion

In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.

<span class="mw-page-title-main">Flavin adenine dinucleotide</span> Redox-active coenzyme

In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which may be in the form of FAD or flavin mononucleotide (FMN). Many flavoproteins are known: components of the succinate dehydrogenase complex, α-ketoglutarate dehydrogenase, and a component of the pyruvate dehydrogenase complex.

<span class="mw-page-title-main">Mixed acid fermentation</span> Biochemical conversion of six-carbon sugars into acids in bacteria

In biochemistry, mixed acid fermentation is the metabolic process by which a six-carbon sugar is converted into a complex and variable mixture of acids. It is an anaerobic (non-oxygen-requiring) fermentation reaction that is common in bacteria. It is characteristic for members of the Enterobacteriaceae, a large family of Gram-negative bacteria that includes E. coli.

<span class="mw-page-title-main">Methanol dehydrogenase</span>

In enzymology, a methanol dehydrogenase (MDH) is an enzyme that catalyzes the chemical reaction:

<span class="mw-page-title-main">Alcohol oxidase</span>

In enzymology, an alcohol oxidase (EC 1.1.3.13) is an enzyme that catalyzes the chemical reaction

In enzymology, a malate dehydrogenase (quinone) (EC 1.1.5.4), formerly malate dehydrogenase (acceptor) (EC 1.1.99.16), is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">NADH peroxidase</span>

In enzymology, a NADH peroxidase (EC 1.11.1.1) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Amine oxidase (copper-containing)</span>

Amine oxidase (copper-containing) (AOC) (EC 1.4.3.21 and EC 1.4.3.22; formerly EC 1.4.3.6) is a family of amine oxidase enzymes which includes both primary-amine oxidase and diamine oxidase; these enzymes catalyze the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. They act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor:

In enzymology, a L-aspartate oxidase (EC 1.4.3.16) is an enzyme that catalyzes the chemical reaction

A polyamine oxidase (PAO) is an enzymatic flavoprotein that oxidizes a carbon-nitrogen bond in a secondary amino group of a polyamine donor, using molecular oxygen as an acceptor. The generalized PAO reaction converts three substrates into three products. Different PAOs with varying substrate specificities exist in different organisms. Phylogenetic analyses suggest that PAOs likely evolved once in eukaryotes and diversified by divergent evolution and gene duplication events, though some prokaryotes have acquired PAOs through horizontal gene transfer.

<span class="mw-page-title-main">Malate dehydrogenase 2</span> Enzyme that oxidizes malate to oxaloacetate in Krebs cycle

Malate dehydrogenase, mitochondrial also known as malate dehydrogenase 2 is an enzyme that in humans is encoded by the MDH2 gene.

<span class="mw-page-title-main">Renalase</span> Mammalian protein found in Homo sapiens

Renalase, FAD-dependent amine oxidase is an enzyme that in humans is encoded by the RNLS gene. Renalase is a flavin adenine dinucleotide-dependent amine oxidase that is secreted into the blood from the kidney.

Oxidation response is stimulated by a disturbance in the balance between the production of reactive oxygen species and antioxidant responses, known as oxidative stress. Active species of oxygen naturally occur in aerobic cells and have both intracellular and extracellular sources. These species, if not controlled, damage all components of the cell, including proteins, lipids and DNA. Hence cells need to maintain a strong defense against the damage. The following table gives an idea of the antioxidant defense system in bacterial system.

References

  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. 1 2 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.
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