Mammalian D-amino Acid Oxidase Research Articles

Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota

The flavoenzyme d-amino acid oxidase (DAAO) is deputed to the degradation of d-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal d-amino acids to generate hydrogen peroxide (H2O2), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1–16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity.

Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access.

D-amino acid oxidase (DAAO) degrades D-amino acids to produce α-ketoacids, hydrogen peroxide and ammonia. DAAO has often been investigated and engineered for industrial and clinical applications. We combined information from literature with a detailed analysis of the structure to engineer mammalian DAAOs. The structural analysis was complemented with molecular dynamics simulations to characterize solvent accessibility and product release mechanisms. We identified non-obvious residues located on the loops on the border between the active site and the secondary binding pocket essential for pig and human DAAO substrate specificity and activity. We engineered DAAOs by mutating such critical residues and characterised the biochemical activity of the resulting variants. The results highlight the importance of the selected residues in modulating substrate specificity, product egress and enzyme activity, suggesting further steps of DAAO re-engineering towards desired clinical and industrial applications.

Quantitative in silico analysis of selective enzyme reaction of mammalian D-amino acid oxidase and acidic D-amino acid oxidase mutants

Quantitative in silico analysis of selective enzyme reaction of mammalian D-amino acid oxidase and acidic D-amino acid oxidase mutants

Competitive Inhibitors Unveil Structure/Function Relationships in Human D-Amino Acid Oxidase.

D-amino acid oxidase (DAAO) catalyzes the oxidative deamination of several neutral D-amino acids and is the enzyme mainly responsible (together with serine racemase) for degrading D-serine (D-Ser) in the central nervous system of mammals. This D-amino acid, which binds the coagonist site of the N-methyl-D-aspartate receptor, is thus a key neuromodulator of glutamatergic neurotransmission. Altered D-Ser metabolism results in several pathological conditions (e.g., amylotrophic lateral sclerosis or schizophrenia, SZ) for which effective “broad spectrum” pharmaceutical drugs are not yet available. In particular, the correlation between reduced D-Ser concentration and SZ led to a renaissance of biochemical interest in human DAAO (hDAAO). In the last 10 years, public and corporate research laboratories undertook huge efforts to study the structural, enzymatic, and physiological properties of the human flavoenzyme and to identify novel effective inhibitors which, acting as pharmaceutical drugs, could decrease hDAAO activity, thus restoring the physiological concentration of D-Ser. Although, none of the identified hDAAO inhibitors has reached the market yet, from a biochemical point of view, these compounds turned out to be invaluable for gaining a detailed understanding of the structure/function relationships at the molecular level in the mammalian DAAO, in particular of the interaction between ligand and the enzyme. This detailed knowledge, together with several recent studies concerning the interaction of the human enzyme with other protein regulative partners, its subcellular localization, and in vivo degradation, contributed to gaining comprehensive knowledge of the structure, function, and physiopathological role of this important human enzyme.

Brain d-amino acids: a novel class of neuromodulators

In Alice in Through the Looking-Glass, and What Alice Found There, Alice proposes to her kitten a looking-glass house, whereupon Lewis Carroll fantasizes a backwards world and raises the question of life’s chirality. Homochirality has been thought to be essential to biology— generating distinct enzymes/receptors to cope with multiple isomers which would pose energetic burdens incompatible with life. Hence, we have D-sugars and L-amino acids. D-Amino acids found in mammalian tissues were assumed to be the by-products of dietary consumption, since plants and bacteria do synthesize D-amino acids. A nagging brain-teaser, for over 40 years, has been the existence of mammalian D-amino acid oxidase and D-aspartate oxidase with particularly high levels in the brain. Like Alice, neurobiologists have now stepped through the looking-glass to characterize at least two D-amino acids, D-serine and D-aspartic acid, that may serve as the important signalling molecules in the nervous and endocrine systems. D-Aspartate was first found in the nervous system of marine mollusks and subsequently in nervous and endocrine tissues of many mammals, including humans. In 1992, Nishikawa and his colleagues developed a high performance liquid chromatography (HPLC) system to separate isomers in biological samples. They confirmed the presence of free D-aspartic acid in the brain of rodent, where they also identified free D-serine. Research by the authors and other groups identified the two enzymes, serine racemase and aspartate racemase, that synthesize D-serine and D-aspartate, respectively. Emerging unanticipated roles for these two amino acids challenge fundamental dogma about cell-to-cell signaling. Thus, D-serine fulfils the criteria of a major, if not the sole, ligand for the strychnineinsensitive glycine modulatory binding site of the N-methyl-D-aspartate receptor (NMDA) subtype of glutamate receptor, which mediates excitatory neurotransmission and cognitive function. D-Aspartate mediates diverse neuroendocrine functions. We are just beginning to understand the importance of this novel class of brain messengers that will soon include additional candidates. Indeed, recent studies suggest that other D-amino acids, such as D-glutamate, N-methyl-D-aspartate, D-alanine and D-glutamine, may also serve as messenger molecules. The expanded recognition of D-amino acids as signalling molecules, along with appreciation of gases as neuromodulators, further alters thinking about what should be a neurotransmitter. This special volume of Amino Acids provides an overview of the current status of our understanding on D-amino acid biology, incorporating contributions from leaders in the field. We have assembled eight review articles that convey recent achievements characterizing the metabolism, brain disposition and roles in synaptic plasticity of D-amino acids, including the recent development of biosensors. The issue also incorporates two orignal studies by Prof Wang and his coworkers who report the contribution of spinal D-amino acid oxidase to bone cancer pain, and by Prof. Hamase and colleagues who demonstrate the alteration in D-serine levels in mice lacking serine racemase and D-amino acid oxidase. J.-P. Mothet (&) Aix Marseille University, CRN2M UMR7286 CNRS, 51 Bd Pierre Dramard, 13344 Marseille Cedex 15, France e-mail: jean-pierre.mothet@univ-amu.fr

Development of an implantable d-serine biosensor for in vivo monitoring using mammalian d-amino acid oxidase on a poly ( o-phenylenediamine) and Nafion-modified platinum–iridium disk electrode

d-serine has been implicated as a brain messenger, promoting not only neuronal signalling but also synaptic plasticity. Thus, a sensitive tool for d-serine monitoring in brain is required to understand the mechanisms of d-serine release from glia cells. A biosensor for direct fixed potential amperometric monitoring of d-serine incorporating mammalian d-amino acid oxidase (DAAO) immobilized on a Nafion coated poly- ortho-phenylenediamine (PPD) modified Pt–Ir disk electrode was therefore developed. The combined layers of PPD and Nafion enhanced the enzyme activity and biosensor efficiency by ∼2-fold compared with each individual layer. A steady state response time ( t 90%) of 0.7 ± 0.1 s ( n = 8) and limit of detection 20 ± 1 nM ( n = 8) were obtained. Cylindrical geometry showed lower sensitivity compared to disk geometry (61 ± 7 μA cm −2 mM −1, ( n = 4), R 2 = 0.999). Interference by ascorbic acid (AA), the main interference species in the central nervous system and other neurochemical electroactive molecules was negligible. Implantation of the electrode and microinjection of d-serine into rat brain striatal extracellular fluid demonstrated that the electrode was capable of detecting d-serine in brain tissue in vivo.

D-Amino acid dehydrogenase from Helicobacter pylori NCTC 11637

Helicobacter pylori is a microaerophilic bacterium, associated with gastric inflammation and peptic ulcers. D-Amino acid dehydrogenase is a flavoenzyme that digests free neutral D-amino acids yielding corresponding 2-oxo acids and hydrogen. We sequenced the H. pylori NCTC 11637 D-amino acid dehydrogenase gene, dadA. The primary structure deduced from the gene showed low similarity with other bacterial D-amino acid dehydrogenases. We purified the enzyme to homogeneity from recombinant Escherichia coli cells by cloning dadA. The recombinant protein, DadA, with 44 kDa molecular mass, possessed FAD as cofactor, and showed the highest activity to D-proline. The enzyme mediated electron transport from D-proline to coenzyme Q(1), thus distinguishing it from D-amino acid oxidase. The apparent K(m) and V(max) values were 40.2 mM and 25.0 micromol min(-1) mg(-1), respectively, for dehydrogenation of D-proline, and were 8.2 microM and 12.3 micromol min(-1) mg(-1), respectively, for reduction of Q(1). The respective pH and temperature optima were 8.0 and 37 degrees C. Enzyme activity was inhibited markedly by benzoate, and moderately by SH reagents. DadA showed more similarity with mammalian D-amino acid oxidase than other bacterial D-amino acid dehydrogenases in some enzymatic characteristics. Electron transport from D-proline to a c-type cytochrome was suggested spectrophotometrically.

Kinetic mechanisms of glycine oxidase from Bacillus subtilis.

The kinetic properties of glycine oxidase from Bacillus subtilis were investigated using glycine, sarcosine, and d-proline as substrate. The turnover numbers at saturating substrate and oxygen concentrations were 4.0 s(-1), 4.2 s(-1), and 3.5 s(-1), respectively, with glycine, sarcosine, and D-proline as substrate. Glycine oxidase was converted to a two-electron reduced form upon anaerobic reduction with the individual substrates and its reductive half-reaction was demonstrated to be reversible. The rates of flavin reduction extrapolated to saturating substrate concentration, and under anaerobic conditions, were 166 s(-1), 170 s(-1), and 26 s(-1), respectively, with glycine, sarcosine, and D-proline as substrate. The rate of reoxidation of reduced glycine oxidase with oxygen in the absence of product (extrapolated rate approximately 3 x 10(4) M(-1) x s(-1)) was too slow to account for catalysis and thus reoxidation started from the reduced enzyme:imino acid complex. The kinetic data are compatible with a ternary complex sequential mechanism in which the rate of product dissociation from the reoxidized enzyme form represents the rate-limiting step. Although glycine oxidase and D-amino acid oxidase differ in substrate specificity and amino acid sequence, the kinetic mechanism of glycine oxidase is similar to that determined for mammalian D-amino acid oxidase on neutral D-amino acids, further supporting a close similarity between these two amine oxidases.

Yeast d-Amino Acid Oxidase: Structural Basis of its Catalytic Properties

The 3D structure of the flavoprotein d-amino acid oxidase (DAAO) from the yeast Rhodotorula gracilis (RgDAAO) in complex with the competitive inhibitor anthranilate was solved (resolution 1.9Å) and structural features relevant for the overall conformation and for catalytic activity are described. The FAD is bound in an elongated conformation in the core of the enzyme. Two anthranilate molecules are found within the active site cavity; one is located in a funnel forming the entrance, and the second is in contact with the flavin. The anchoring of the ligand carboxylate with Arg285 and Tyr223 is found for all complexes studied. However, while the active site group Tyr238-OH interacts with the carboxylate in the case of the substrate d-alanine, of d-CF3-alanine, or of l-lactate, in the anthranilate complex the phenol group rotates around the C2–C3 bond thus opening the entrance of the active site, and interacts there with the second bound anthranilate. This movement serves in channeling substrate to the bottom of the active site, the locus of chemical catalysis. The absence in RgDAAO of the “lid” covering the active site, as found in mammalian DAAO, is interpreted as being at the origin of the differences in kinetic mechanism between the two enzymes. This lid has been proposed to regulate product dissociation in the latter, while the side-chain of Tyr238 might exert a similar role in RgDAAO. The more open active site architecture of RgDAAO is the origin of its much broader substrate specificity. The RgDAAO enzyme forms a homodimer with C2 symmetry that is different from that reported for mammalian d-amino acid oxidase. This different mode of aggregation probably causes the differences in stability and tightness of FAD cofactor binding between the DAAOs from different sources.

The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site.

The structure of L-amino acid oxidase (LAAO) from Calloselasma rhodostoma has been determined to 2.0 A resolution in the presence of two ligands: citrate and o-aminobenzoate (AB). The protomer consists of three domains: an FAD-binding domain, a substrate-binding domain and a helical domain. The interface between the substrate-binding and helical domains forms a 25 A long funnel, which provides access to the active site. Three AB molecules are visible within the funnel of the LAAO-AB complex; their orientations suggest the trajectory of the substrate to the active site. The innermost AB molecule makes hydrogen bond contacts with the active site residues, Arg90 and Gly464, and the aromatic portion of the ligand is situated in a hydrophobic pocket. These contacts are proposed to mimic those of the natural substrate. Comparison of LAAO with the structure of mammalian D-amino acid oxidase reveals significant differences in their modes of substrate entry. Furthermore, a mirror-symmetrical relationship between the two substrate-binding sites is observed which facilitates enantiomeric selectivity while preserving a common arrangement of the atoms involved in catalysis.

Limited proteolysis and X-ray crystallography reveal the origin of substrate specificity and of the rate-limiting product release during oxidation of D-amino acids catalyzed by mammalian D-amino acid oxidase.

Limited proteolysis of D-amino acid oxidase holoenzyme with trypsin cleaves the protein at Arg 221 and near the C-terminus, producing stable 25, 13.4, and 2 kDa polypeptides [Torri-Tarelli, G., Vanoni, M. A., Negri, A., & Curti, B. (1990) J. Biol. Chem. 265, 21242-21246]. The 25 and 13.4 kDa polypeptides remain associated to form a nicked D-amino acid oxidase species. This nicked protein form maintains the ability to bind FAD, but exhibits altered catalytic efficiency toward the oxidation of various D-amino acids when compared to native DAAO. Changes in substrate specificity were first monitored by measuring the activity in the presence of different amino acid substrates at various times during proteolysis. Three amino acid substrates were then selected for further analysis of the properties of the nicked D-amino acid oxidase species produced by limited tryptic proteolysis: D-serine, D-arginine, and D-alanine. The three D-amino acids represented limiting cases of the observed changes of enzyme activity on nicking: loss of activity, increase of activity, and minor activity changes, respectively. D-serine was found to be no longer a substrate of D-amino acid oxidase. D-arginine exhibited a 2.5-fold increased apparent maximum velocity although its Km value increased 2-fold with the nicked enzyme in comparison to the native species. D-alanine was oxidized 1.5-fold faster by the nicked D-amino acid oxidase at infinite substrate concentration, and its Km value increased approximately 4-fold. The Kd for benzoate, which was determined kinetically with D-alanine as the enzyme substrate, increased 17-fold in the nicked species. Primary deuterium kinetic isotope effects on V and V/K during the oxidation of D-alanine were also measured. (D)V/K increased from 1.4 +/- 0.2 to 1.8 +/- 0.3 on nicking, while (D)V increased from 1.04 +/- 0.1 to 2.53 +/- 0.5. All the observed changes of the values of the kinetic parameters and of the observed isotope effects are consistent with the hypothesis that nicking of D-amino acid oxidase at position 221 decreases the strength of binding of both substrates and products to the enzyme active site. The information obtained by limited tryptic proteolysis nicely complements that gathered from the analysis of the three-dimensional structure of D-amino acid oxidase in complex with benzoate, which was recently determined [Mattevi, A., Vanoni, M. A., Todone, F., Rizzi, M., Teplyakov, A., Coda, A., Bolognesi, M., & Curti, B. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 7496-7501]. Arginine 221 is part of the 216-228 loop that covers the active site and contributes residues to substrate binding and catalysis. The limited proteolysis data support the hypothesis that this loop acts as a lid on the active site and controls both substrate specificity and the rate of turnover of D-amino acid oxidase.

CDNA cloning and expression of the flavoprotein D-aspartate oxidase from bovine kidney cortex.

The isolation and sequencing of the complete cDNA coding for a d-aspartate oxidase, as well as the overexpression of the recombinant active enzyme, are reported for the first time. This 2022 bp cDNA, beside the coding portion, comprises a 5' untranslated tract and the whole 3' region including the polyadenylation signal and the poly(A) tail. The encoded protein comprises 341 amino acids, with the last three residues (-Ser-Lys-Leu) representing a peroxisomal targeting signal 1 (PTS1), hitherto unknown for this protein. The overexpression of recombinant d-aspartate oxidase was achieved in a prokaryotic system, and a soluble and active enzyme was obtained which accounted for about 10% of total bacterial protein. Comparisons with the known cDNAs for mammalian d-amino acid oxidase, another peroxisomal enzyme, are also made. The close structural and functional similarities shared by these enzymes at the protein level are not reflected at the nucleic acid level.

Oxidation of anionic nitroalkanes by flavoenzymes, and participation of superoxide anion in the catalysis

The reactivities of anionic nitroalkanes with 2-nitropropane dioxygenase of Hansenula mrakii, glucose oxidase of Aspergillus niger, and mammalian d-amino acid oxidase have been compared kinetically. 2-Nitropropane dioxygenase is 1200 and 4800 times more active with anionic 2-nitropropane than d-amino acid oxidase and glucose oxidase, respectively. The apparent K m values for anionic 2-nitropropane are as follows: 2-nitropropane dioxygenase, 1.61 m m; glucose oxidase, 16.7 m m; and d-amino acid oxidase, 11.1 m m. Anionic 2-nitropropane undergoes an oxygenase reaction with 2-nitropropane dioxygenase and glucose oxidase, and an oxidase reaction with d-amino acid oxidase. In contrast, anionic nitroethane is oxidized through an oxygenase reaction by 2-nitropropane dioxygenase, and through an oxidase reaction by glucose oxidase. All nitroalkane oxidations by these three flavoenzymes are inhibited by Cu and Zn-superoxide dismutase of bovine blood, Mn-superoxide dismutases of bacilli, Fe-superoxide dismutase of Serratia marcescens, and other O 2 ⨪ scavengers such as cytochrome c and NADH, but are not affected by hydroxyl radical scavengers such as mannitol. None of the O 2 ⨪ scavengers tested affected the inherent substrate oxidation by glucose oxidase and d-amino acid oxidase. Furthermore, the generation of O 2 ⨪ in the oxidation of anionic 2-nitropropane by 2-nitropropane dioxygenase was revealed by ESR spectroscoy. The ESR spectrum of anionic 2-nitropropane plus 2-nitropropane dioxygenase shows signals at g 1 = 2.007 and g 11 = 2.051, which are characteristic of O 2 ⨪ . The O 2 ⨪ generated is a catalytically essential intermediate in the oxidation of anionic nitroalkanes by the enzymes.

The inhibition of mammalian d-amino acid oxidase by metabolites and drugs. Inferences concerning physiological function

The inhibition of d-amino acid oxidase (EC 1.4.3.3) by a large number of metabolites and drugs is reported. When the substrate is an adduct (thiazolidine-2-carboxylate) formed from cysteamine and glyoxylate, at least five different mechanisms of inhibition are possible, and examples of each are given. Effective inhibitors include (a) some adenosine containing nucleotides, in particular ADP, AMP, ADP ribose, NADH, NADPH and dephospho-CoA; (b) diuretics, especially furosemide, ethacrynic acid, and mersalyl; (c) anti-inflammatory agents, such as salicylate, indomethacin, phenylbutazone, acetylsalicylate, mefenamic, and flufenamic acids; (d) hypoglycemic, hypocalcemic, and hypolipidemic compounds, including 5-methylpyrazole-3-carboxylate, pyrrole-2-carboxylate, 5-methylthiophene-2-carboxylate, thiophene-2-carboxylate, benzoate, and nicotinate; (e) aldehydes, for example, formaldehyde, acetaldehyde, and succinate semialdehyde; (f) thiols, especially β-aminothiols such as cysteine and penicillamine; (g) tropolone, and (h) hydrogen peroxide. The rate of the reaction is also very sensitive to oxygen presure; at pH 7.4 and 25°C the K m for O 2 is 1.1 m M. These data, in conjunction with literature information concerning the biological affects of such compounds, are used to suggest possible physiological processes in which the d-amino acid oxidase reaction may be involved. Although such correlations based on circumstantial evidence are not conclusive, they suggest that d-amino acid oxidase may play a major role in the control of metabolism in animals. Some processes in which it may participate include maintenance of ion and water balance in the kidney, inflammatory response, transmission of nerve impulses, sensing of O 2 concentration, control of cell growth, and as part of an intracellular messenger system for some hormones, especially insulin.

Reactions of cysteamine and other amine metabolites with glyoxylate and oxygen catalyzed by mammalian D-amino acid oxidase.

Pig kidney D-amino acid oxidase [D-amino-acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3] catalyzes a rapid uptake of oxygen when high concentrations (50-100 mM) of glyoxylate and the following amines are present under usual assay conditions (pH 8.3): cysteamine, 2-aminoethanol, putrescine, D,L-1-amino-2-propanol, D,L-2-amino-1-propanol, 3-amino-1-propanol, D,L-octopamine, ethylenediamine, and L-cysteine ethyl ester. Notable physiological amines that do not support a rapid O2 reaction under the above conditions include histamine, serotonin, epinephrine, norepinephrine, spermidine, spermine, and cadaverine. A more detailed kinetic investigation of the reactions involving the first four reactive amines listed above indicated that the cysteamine reaction proceeds at a rapid rate even when cysteamine and glyoxylate are present at less than millimolar concentrations, but greater than millimolar concentrations are needed in the other amine reactions in order to observe a reasonable rate. At low concentrations and pH 7.4, the cysteamine-glyoxylate substrate (presumably thiazolidine-2-carboxylic acid) reacts an order of magnitude faster than any other known D-amino acid oxidase substrate. Considerable circumstantial evidence suggests that the reaction involving cysteamine is occurring physiologically, but the reactions of other amines would be occurring in the cell at a very low rate, if at all. It is proposed that the product of the enzymic reaction may be a metabolic effector that can modify the reactivity of proteins or nucleic acids by covalent attachment.

Effects of metal ions and sulfhydryl inhibitors on glucose metabolism by adipose tissue.

ARTICLESEffects of metal ions and sulfhydryl inhibitors on glucose metabolism by adipose tissuePK Dixit, and A LazarowPK Dixit, and A LazarowPublished Online:01 Oct 1967https://doi.org/10.1152/ajplegacy.1967.213.4.849MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByPeroxisomal Oxidases and Suggestions for the Mechanism of Action of Insulin and Other Hormones22 November 2006Arsenic Exposure and Type 2 Diabetes: A Systematic Review of the Experimental and Epidemiologic EvidenceEnvironmental Health Perspectives, Vol. 114, No. 5Boron, Manganese, Molybdenum, Nickel, Silicon and Vanadium14 December 2009Enzymatic and cellular level effects of chromium∗Toxicological & Environmental Chemistry, Vol. 19, No. 3-4Enzymatic and cellular level effects of cadmiumToxicological & Environmental Chemistry, Vol. 19, No. 3-4The inhibition of mammalian d-amino acid oxidase by metabolites and drugs. Inferences concerning physiological functionBioorganic Chemistry, Vol. 11, No. 3Multiple effects of sulphydryl reagents on sugar transport by rat soleus muscleBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 689, No. 2Serum enzyme changes due to trace amounts of some transition metal ions on the induction of experimental diabetes1 June 1980 | Zeitschrift für Ernährungswissenschaft, Vol. 19, No. 2Serum mineral changes due to exogenous ATP and certain trace elements in experimental diabetes1 March 1979 | Zeitschrift für Ernährungswissenschaft, Vol. 18, No. 1Endogenous hydrogen peroxide and peroxidative metabolism in adipocytes in response to insulin and sulfhydryl reagentsBiochemical Pharmacology, Vol. 27, No. 22Reduced nicotinamide adenine dinucleotide phosphate oxidase in adipocyte plasma membrane and its activation by insulinArchives of Biochemistry and Biophysics, Vol. 184, No. 1The effect of ATP and certain trace elements on the induction of experimental diabetes1 September 1977 | Zeitschrift für Ernährungswissenschaft, Vol. 16, No. 3Trace Metals in EndocrinologyMedical Clinics of North America, Vol. 60, No. 4Effects of sulfhydryl inhibition on the regulation of basal lipolysis and glucose uptake in human adipose tissueBiochemical Pharmacology, Vol. 24, No. 9Sensitization of adipose tissue to insulin by rat serumNaunyn-Schmiedeberg's Archives of Pharmacology, Vol. 283, No. 1The non-involvement of cysteine or cystine in the membrane receptor site of insulinActa Diabetologica Latina, Vol. 9, No. 1Glucose Transport in Plasma Membrane Vesicles from Rat Adipose TissueJournal of Biological Chemistry, Vol. 247, No. 9Transport of Carbohydrates by Animal CellsRegulation of Pyrimidine Ribonucleoside Incorporation in Isolated Bone CellsJournal of Biological Chemistry, Vol. 246, No. 14Non-suppressible insulin-like activity of human serumBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 230, No. 1Sulfhydryl Groups in Membrane Structure and FunctionStudies of the Insulin-like Actions of Thiols upon Isolated Fat CellsJournal of Biological Chemistry, Vol. 245, No. 1Methodology of Zinc Determinations and The Role of Zinc in Biochemical ProcessesInsulin-Receptor Interaction in Isolated Fat CellsJournal of Biological Chemistry, Vol. 244, No. 19The effect of sulfhydryl blockade on insulin action and glucose transport in isolated adipose tissue cellsBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 177, No. 3The effect of zinc on the uptake of glucose by adipose tissueBiochimica et Biophysica Acta (BBA) - General Subjects, Vol. 177, No. 3Incorporation and utilization of radioglucose in the fish embryoOryzias latipes during teratogenesisTeratology, Vol. 1, No. 4 More from this issue > Volume 213Issue 4October 1967Pages 849-856 Copyright & PermissionsCopyright © 1967 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1967.213.4.849PubMed6051180History Published online 1 October 1967 Published in print 1 October 1967 Metrics

Competitive inhibitive action of normal fatty acids on mammalian D-amino acid oxidase.

Some of the short chain normal fatty acids are shown to be competitive inhibitors of the D-amino acid oxidase of rat kidney. In contrast to benzoate, which is a competitive inhibitor of this enzyme and of the ophio-L-amino acid oxidase of cobra venom, sodium pentanoate inhibits only the kidney enzyme.