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At least 19 recordsLinked to original sources
PubMed2001

Final report on the safety assessment of Cocoyl Sarcosine, Lauroyl Sarcosine, Myristoyl Sarcosine, Oleoyl Sarcosine, Stearoyl Sarcosine, Sodium Cocoyl Sarcosinate, Sodium Lauroyl Sarcosinate, Sodium Myristoyl Sarcosinate, Ammonium Cocoyl Sarcosinate, and Ammonium Lauroyl Sarcosinate.

This safety assessment addresses cosmetic ingredients that are N-acyl derivatives of sarcosine and are generally referred to as acyl sarcosines, and those that are salts, known generally as acyl sarcosinates. Previous assessments have addressed the safety of each of the fatty acids that appear in these acyl sarcosines and sarcosinates (Coconut Acid, Oleic Acid, Lauric Acid, and Myristic Acid). In each case the fatty acid was either safe for use or safe as used in cosmetic formulations. Acyl sarcosines are considered modified fatty acids with greater solubility and increased acidity of the carboxylic acid group compared to the parent fatty acid. They are used in a large number of cosmetic formulations as hair-conditioning agents and surfactant-cleansing agents. In soaps, concentrations are reported to be as high as 12.9%. These ingredients have low oral toxicity in rats. Although cytotoxic to Chinese hamster cells in culture, acyl sarcosines and sarcosinates are not mutagenic in those cells, nor in bacterial cells in culture. Carcinogenicity data were not available. These ingredients are nonirritating and nonsensitizing to animal and human skin, although they can enhance the penetration of other ingredients through the skin. For that reason, caution should be exhibited in formulating cosmetic products that contain these ingredients in combination with other ingredients whose safety is based on their lack of absorption or where dermal absorption is a concern (e.g., HC Yellow No. 4, Disperse Yellow 3). Because sarcosine can be nitrosated to form N-nitrososarcosine, a known animal carcinogen, these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed. With the above caveat, and based on the available data, it was concluded that these acyl sarcosines and sarcosinates are safe as used in rinse-off products. They may be safely used in leave-on products at concentrations up to 5%, the highest concentration tested in clinical irritation and sensitization studies. Oleoyl Sarcosine is used as a corrosion inhibitor in some aerosol products, at extremely low concentrations. In this circumstance, the ingredient is not being used as a cosmetic ingredient and this report is not intended to limit that use. Because of the absence of data on inhalation toxicity, however, it was concluded that the available data were not sufficient to support the safety of acyl sarcosines and sarcosinates as cosmetic ingredients in products where they are likely to be inhaled.

Administration, Inhalation↗
PubMed1993

Preparation and properties of recombinant corynebacterial sarcosine oxidase: evidence for posttranslational modification during turnover with sarcosine.

The genes encoding the four subunits of sarcosine oxidase from Corynebacterium sp. P-1 were isolated and overexpressed in a single step by using indicator plates to screen a genomic library for colonies that generated hydrogen peroxide in a sarcosine-dependent reaction. The genomic library was constructed by inserting size-fractionated genomic DNA, previously subjected to partial digestion by Sau3AI, into pBluescript II SK (+). At least 1.0 kb, but less than 4.0 kb, can be deleted from the 3' end of the original cornyebacterial insert (7.3 kb) without affecting sarcosine oxidase expression, consistent with the estimated 5.0-kb operon size. Recombinant sarcosine oxidase is isolated as a heterotetramer containing equimolar amounts of covalent and noncovalent flavin, identical to that observed for enzyme isolated from Corynebacterium sp. P-1. Despite its similar flavin content, recombinant enzyme exhibits significantly different spectral properties than enzyme from Corynebacterium sp. P-1 (values shown in parentheses) [epsilon 450 = 9.7 (12.7) mM-1 cm-1; A368/A450 = 1.0 (0.83); A280/A450 = 16.9 (12.2)]. This difference is due to the fact that about half of the covalent flavin in recombinant enzyme forms a reversible covalent 4a-adduct with a cysteine residue (lambda max = 383 nm; epsilon 383 = 7.3 mM-1 cm-1). The equilibrium is shifted in favor of adduct dissociation by oxidizing the cysteine residue with hydrogen peroxide or by alkylation with methyl methanethiosulfonate in a reaction that is fully reversible upon addition of excess dithiothreitol. The cysteine residue is also oxidized during aerobic turnover with sarcosine. Reaction of the cysteine residue with hydrogen peroxide (or a precursor) formed during turnover partially competes with the release of hydrogen peroxide into solution, as judged by the effect of catalase on this reaction. Although the same specific activity is observed for recombinant enzyme and enzyme from Corynebacterium sp. P-1, the recombinant enzyme exhibits a pronounced lag in an NADH peroxidase-coupled assay. The lag is eliminated by prior disruption of the 4a-thiolate adduct via reaction with hydrogen peroxide or methyl methanethiosulfonate. The results show that the 4a-thiolate adduct is an inactive form of sarcosine oxidase that can be activated by reaction with sarcosine in what appears to be the first example of a posttranslational modification associated with turnover. Complete activation occurs in vivo when sarcosine oxidase is produced in Corynebacterium sp. P-1, where enzyme synthesis is induced by growth of the organism with sarcosine as the source of carbon and energy.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatography, Gel↗
PubMed2000

Monomeric sarcosine oxidase: 2. Kinetic studies with sarcosine, alternate substrates, and a substrate analogue.

Monomeric sarcosine oxidase (MSOX) is a flavoenzyme that catalyzes the oxidative demethylation of sarcosine (N-methylglycine) to yield glycine, formaldehyde, and hydrogen peroxide. MSOX can oxidize other secondary amino acids (N-methyl-L-alanine, N-ethylglycine, and L-proline), but N,N-dimethylglycine, a tertiary amine, is not a substrate. N-Methyl-L-alanine is a good alternate substrate, exhibiting a k(cat) value (8700 min(-)(1)) similar to sarcosine (7030 min(-)(1)). Turnover with L-proline (k(cat) = 25 min(-)(1)) at 25 degrees C occurs at less than 1% of the rate observed with sarcosine. MSOX is converted to a two-electron reduced form upon anaerobic reduction with sarcosine or L-proline. No evidence for a spectrally detectable intermediate was obtained in reductive half-reaction studies with L-proline. The reductive half-reaction with L-proline at 4 degrees C exhibited saturation kinetics (k(lim) = 6.0 min(-)(1), K(d) = 260 mM) and other features consistent with a mechanism in which a practically irreversible reduction step (E(ox). S --> E(red).P) with a rate constant, k(lim), is preceded by a rapidly attained equilibrium (K(d)) between free E and the E.S complex. Steady-state kinetic studies with sarcosine and N-methyl-L-alanine in the absence or presence of a dead-end inhibitor (pyrrole-2-carboxylate) indicate that catalysis proceeds via a "modified" ping pong mechanism in which oxygen reacts with E(red).P prior to the dissociation of the imino acid product. In this mechanism, double reciprocal plots will appear nearly parallel (as observed) if the reduction step is nearly irreversible. A polar mechanism, involving formation of a covalent 4a-flavin-substrate adduct is one of several plausible mechanisms for sarcosine oxidation. Thiols are known to form similar 4a-flavin adducts. MSOX does not form a 4a-adduct with thioglycolate but does form a charge-transfer complex that undergoes an unanticipated one-electron-transfer reaction to yield the anionic flavin radical.

Alanine↗
PubMed2002

Single crystal EPR studies on Mn(II)-doped sarcosine cadmium chloride and sarcosine cadmium bromide: study of zero-field splitting tensor in iso-structural complexes.

EPR spectra of single crystals of Mn(II)-doped sarcosine cadmium chloride and sarcosine cadmium bromide are studied in Q-band and in X-band at room temperature. Two magnetically inequivalent sites are observed in both the lattices in a distorted octahedral environment. The spin-Hamiltonian parameters are extracted and are found to have a rhombic symmetry. The angular variation of the zero-field transitions is simulated for one of the sites with an asymmetric zero-field tensor D = 480 x 10(-4) cm(-1), E = -115 x 10(-4) cm(-1) and a = 10 x 10(-4) cm(-1) for Mn(II) in sarcosine cadmium chloride and with D = 460 x 10(-4) cm(-1) E = -98 x 10(-4) cm(-1) and a = 10 x 10(-4) cm(-1) for Mn(II) in sarcosine cadmium bromide. The observed large value of zero-field tensor is due to the steric effects of the crystal packing caused by the ligands. Matumura's plot predicts an average covalency of 8.8 and 7.7% for the manganese-ligand bond in SCC and SCB lattices respectively.

Bromides↗
PubMed2001

Characterization of glycine sarcosine N-methyltransferase and sarcosine dimethylglycine N-methyltransferase.

Glycine betaine is accumulated in cells living in high salt concentrations to balance the osmotic pressure. Glycine sarcosine N-methyltransferase (GSMT) and sarcosine dimethylglycine N-methyltransferase (SDMT) of Ectothiorhodospira halochloris catalyze the threefold methylation of glycine to betaine, with S-adenosylmethionine acting as the methyl group donor. These methyltransferases were expressed in Escherichia coli and purified, and some of their enzymatic properties were characterized. Both enzymes had high substrate specificities and pH optima near the physiological pH. No evidence of cofactors was found. The enzymes showed Michaelis-Menten kinetics for their substrates. The apparent K(m) and V(max) values were determined for all substrates when the other substrate was present in saturating concentrations. Both enzymes were strongly inhibited by the reaction product S-adenosylhomocysteine. Betaine inhibited the methylation reactions only at high concentrations.

Bacterial Proteins↗
PubMed1991

Sarcosine kinetics in pigs by infusion of [1-14C]sarcosine: use for refining estimates of glycine and threonine kinetics.

To investigate in vivo the interconversion between glycine (Gly) and its N-methyl product sarcosine (Sar), [1-13C]Gly and [1-14C]Sar were infused into hourly fed pigs receiving diets with low- and high-threonine levels. An open two-pool model was developed to calculate Sar demethylation (DM) and Gly methylation (GM). During [1-14C]Sar infusion, intracellular Gly specific radioactivities (SA) in the liver and kidney were higher than plasma Gly SA, suggesting that demethylation of Sar occurred in those tissues. DM estimated by using hippuric acid (HA) as the production pool had a mean value of 1.55 mumol.kg-1.h-1, similar to the Sar production rate (mean 1.85 mumol.kg-1.h-1). GM was undetectable (less than 0.5 mumol.kg-1.h-1). These results suggest that, in fed pigs, Sar is produced mainly from choline catabolism and is degraded only to Gly in liver and kidney. On the assumption that Sar degradation gave rise only to Gly, the production rate of Gly (Gly PR) was calculated from [1-13C]Gly and [1-14C]Sar infusions using either the primary pools (plasma Gly and HA, respectively) or the secondary pools (HA and plasma Gly, respectively). The results were explained by a liver-plasma Gly exchange model. The whole body Gly irreversible loss, i.e., direct loss from plasma and liver, was calculated from this model to be 832 +/- 58 mumol.kg-1.h-1, showing that the estimation of Gly PR with [1-13C]Gly infusion and plasma Gly enrichment (599 +/- 56 mumol.kg-1.h-1) was a significant underestimate of the true value.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Folate utilization by monomeric versus heterotetrameric sarcosine oxidases.

There are two types of bacterial sarcosine oxidases. The heterotetrameric enzymes contain subunits ranging in size from about 10 to 100 kDa, noncovalently bound FAD and NAD+, and covalently bound FMN attached to the beta subunit (42-45 kDa). Monomeric sarcosine oxidases are similar in size to the beta subunit in the heterotetramers and contain covalently bound FAD. Formaldehyde formation during sarcosine oxidation by several heterotetrameric sarcosine oxidases was suppressed in the presence of 50 microM [6S]-tetrahydrofolate, accompanied by a 25-50% increase in the rate of sarcosine oxidation. In contrast, [6S]-tetrahydrofolate caused only a modest decrease in the rate of formaldehyde production with monomeric sarcosine oxidases (approximately 25%), an effect which was virtually entirely attributable to an accompanying decrease in the rate of sarcosine oxidation. In the presence of 100 microM [6R,S]-tetrahydropteroyltriglutamate [H4Pte(Glu)3], the heterotetrameric enzymes catalyzed the formation of 5,10-methylenetetrahydropteroyltriglutamate [5,10-CH2-H4Pte(Glu)3] at a rate which was 35-60% faster than the rate of sarcosine oxidation in the absence of folate. An apparent Km value of 3.1 microM was estimated for [6S]-H4Pte(Glu)3 with the heterotetrameric corynebacterial sarcosine oxidase. In contrast, slow formation of 5,10-CH2-H4Pte(glu)3 was detected during sarcosine oxidation with monomeric sarcosine oxidases, attributable to the nonenzymatic reaction of free formaldehyde with H4Pte(Glu)3. The results show that only the heterotetrameric sarcosine oxidases can use tetrahydrofolates as substrates and, in this regard, they resemble mammalian sarcosine and dimethylglycine dehydrogenases.

Corynebacterium↗
PubMed1971

Transport and metabolism of sarcosine in hypersarcosinemic and normal phenotypes.

An adolescent male proband with hypersarcosinemia was discovered incidentally in a French-Canadian family; no specific disease was associated with the trait. The hypersarcosinemia is not diminished by dietary folic acid even in pharmacologic doses (30 mg/day). The normal absence of sarcosine dehydrogenase in cultured human skin fibroblasts and in leukocytes was confirmed, thus eliminating these tissues as useful sources for further investigation of mutant sarcosinemic phenotypes and genotypes. The response in plasma of sarcosine and glycine, after sarcosine loading, distinguished the normal subject from the subjects who were presumably homozygous and heterozygous for the hypersarcosinemia allele. Sarcosine clearance from plasma was delayed greatly (t(1/2), 6.1 hr) in the presumed homozygote and slightly (t(1/2), 2.2 hr) in the presumed heterozygote, while plasma glycine remained constant in the former and rose in the latter. Normal subjects clear sarcosine from plasma rapidly (t(1/2), 1.6 hr) while their plasma glycine trend is downward. The phenotypic responses suggest that hypersarcosinemia is an autosomal recessive trait in this pedigree. Renal tubular transport of sarcosine was normal in the proband even though he presumably lacked the sarcosine oxidation which should normally occur in kidney. Sarcosine catabolism is thus not important for its own renal uptake. Sarcosine interacts with proline and glycine during its absorption in vivo. Studies in vitro in rat kidney showed that sarcosine transport is mediated, saturable, and energy dependent. Sarcosine has no apparent transport system of its own; it uses the low K(m) transport systems for L-proline and glycine to a minor extent and a high K(m) system shared by these substances for the major uptake at concentrations encountered in hypersarcosinemia. Intracellular sarcosine at high concentration will exchange with glycine on one of these systems, which may explain a paradoxical improvement in renal transport of glycine after sarcosine loading in the hypersarcosinemic proband.

Absorption↗
PubMed1985

Enzymatic properties of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver.

Dimethylglycine dehydrogenase (EC 1.5.99.2) and sarcosine dehydrogenase (EC 1.5.99.1) are flavoproteins which catalyze the oxidative demethylation of dimethylglycine to sarcosine and sarcosine to glycine, respectively. During these reactions tightly bound tetrahydropteroylpentaglutamate (H4PteGlu5) is converted to 5,10-methylene tetrahydropteroylpentaglutamate (5,10-CH2-H4PteGlu5), although in the absence of H4PteGlu5, formaldehyde is produced. Single turnover studies using substrate levels of the enzyme (2.3 microM) showed pseudo-first-order kinetics, with apparent first-order rate constants of 0.084 and 0.14 s-1 at 23 and 48.3 microM dimethylglycine, respectively, for dimethylglycine dehydrogenase and 0.065 s-1 at 47.3 microM sarcosine for sarcosine dehydrogenase. The rates were identical in the absence or presence of bound tetrahydropteroylglutamate (H4PteGlu). Titration of the enzymes with substrate under anaerobic conditions did not disclose the presence of an intermediate semiquinone. The effect of dimethylglycine concentration upon the rate of the dimethylglycine dehydrogenase reaction under aerobic conditions showed nonsaturable kinetics suggesting a second low-affinity site for the substrate which increases the enzymatic rate. The Km for the high-affinity active site was 0.05 mM while direct binding for the low-affinity site could not be measured. Sarcosine and dimethylthetin are poor substrates for dimethylglycine dehydrogenase and methoxyacetic acid is a competitive inhibitor at low substrate concentrations. At high dimethylglycine concentrations, increasing the concentration of methoxyacetic acid produces an initial activation and then inhibition of dimethylglycine dehydrogenase activity. When these compounds were added in varying concentrations to the enzyme in the presence of dimethylglycine, their effects upon the rate of the reaction were consistent with the presence of a second low-affinity binding site on the enzyme which enhances the reaction rate. When sarcosine is used as the substrate for sarcosine dehydrogenase the kinetics are Michaelis-Menten with a Km of 0.5 mM for sarcosine. Also, methoxyacetic acid is a competitive inhibitor of sarcosine dehydrogenase with a Ki of 0.26 mM. In the absence of folate, substrate and product determinations indicated that 1 mol of formaldehyde and of sarcosine or glycine were produced for each mole of dimethylglycine or sarcosine consumed with the concomitant reduction of 1 mol of bound FAD.

Anaerobiosis↗
PubMed1999

Cloning and mapping of the cDNA for human sarcosine dehydrogenase, a flavoenzyme defective in patients with sarcosinemia.

Sarcosine dehydrogenase is a liver mitochondrial matrix flavoenzyme that is defective in patients with sarcosinemia, a rare autosomal metabolic defect characterized by elevated levels of sarcosine in blood and urine. Some patients also exhibit mental retardation and growth failure. A full-length cDNA for human sarcosine dehydrogenase was isolated from an adult liver cDNA library. The first 22 residues in the deduced amino acid sequence exhibit features expected for a mitochondrial targeting sequence. The predicted mass of the mature human liver sarcosine dehydrogenase (99,505 Da) is in good agreement with that observed for rat liver sarcosine dehydrogenase ( approximately 100,000 Da). Human sarcosine dehydrogenase exhibits 89% identity with rat liver sarcosine dehydrogenase and strong homology ( approximately 35% identity) with rat liver dimethylglycine dehydrogenase, a sarcosine dehydrogenase-related protein from Rhodobacter capsulatus, and the regulatory subunit from bovine pyruvate dehydrogenase phosphatase. The human sarcosine dehydrogenase gene is at least 75.3 kb long and located on chromosome 9q34. The adult human liver clone is assembled from 21 exons (1-6, 7a, 8a, 9-21). Two smaller cDNA clones, isolated from adult liver and infant brain libraries, were assembled from the same sarcosine dehydrogenase gene by the use of alternate polyadenylation and splice sites. This is the first report of the genomic structure of the sarcosine dehydrogenase gene in any species. The observed chromosomal location is consistent with genetic studies with a mouse model for sarcosinemia that map the mouse gene to a region of mouse chromosome 2 syntenic with human 9q33-q34. The availability of the SDH gene sequence will enable characterization of the genotypes of sarcosinemia patients with different phenotypes.

Adult↗
PubMed2004

Characterization and metabolic function of a peroxisomal sarcosine and pipecolate oxidase from Arabidopsis.

Sarcosine oxidase (SOX) is known as a peroxisomal enzyme in mammals and as a sarcosine-inducible enzyme in soil bacteria. Its presence in plants was unsuspected until the Arabidopsis genome was found to encode a protein (AtSOX) with approximately 33% sequence identity to mammalian and bacterial SOXs. When overexpressed in Escherichia coli, AtSOX enhanced growth on sarcosine as sole nitrogen source, showing that it has SOX activity in vivo, and the recombinant protein catalyzed the oxidation of sarcosine to glycine, formaldehyde, and H(2) O(2) in vitro. AtSOX also attacked other N-methyl amino acids and, like mammalian SOXs, catalyzed the oxidation of l-pipecolate to Delta(1)-piperideine-6-carboxylate. Like bacterial monomeric SOXs, AtSOX was active as a monomer, contained FAD covalently bound to a cysteine residue near the C terminus, and was not stimulated by tetrahydrofolate. Although AtSOX lacks a typical peroxisome-targeting signal, in vitro assays established that it is imported into peroxisomes. Quantitation of mRNA showed that AtSOX is expressed at a low level throughout the plant and is not sarcosine-inducible. Consistent with a low level of AtSOX expression, Arabidopsis plantlets slowly metabolized supplied [(14)C]sarcosine to glycine and serine. Gas chromatography-mass spectrometry analysis revealed low levels of pipecolate but almost no sarcosine in wild type Arabidopsis and showed that pipecolate but not sarcosine accumulated 6-fold when AtSOX expression was suppressed by RNA interference. Moreover, the pipecolate catabolite alpha-aminoadipate decreased 30-fold in RNA interference plants. These data indicate that pipecolate is the endogenous substrate for SOX in plants and that plants can utilize exogenous sarcosine opportunistically, sarcosine being a common soil metabolite.

Amino Acid Sequence↗
PubMed1983

Variability in the phenotypic expression of abnormal sarcosine metabolism in a family.

A retarded child with hypersarcosinemia and his family were studied by loading tests to determine the probable site of his defect. On the basis of his response to folate treatment, a partially-reversible defect in the formation of activated formaldehyde in the reaction catalyzed by sarcosine dehydrogenase was considered to be the most likely site. During a glycine loading test, sarcosine levels in the plasma and urine increased, indicating that the direct transmethylation of glycine to sarcosine could occur in this patient. The father of the proband tolerated a load of sarcosine poorly, resembling the proband in his plasma sarcosine levels. No evidence that glycine could be transmethylated to sarcosine was found in the father, despite the fact that his peak glycine level was four times higher than the proband's. These findings provide indirect evidence that sarcosine formation may be affected by two additional components besides the apo moiety of sarcosine dehydrogenase, the availability of tetrahydrofolic acid as a one carbon unit carrier and the integrity of the transmethylase which catalyzes the direct transmethylation of glycine to sarcosine.

Adult↗
PubMed2006

Spectral and kinetic characterization of the michaelis charge transfer complex in monomeric sarcosine oxidase.

Monomeric sarcosine oxidase is a flavoenzyme that catalyzes the oxidation of the methyl group in sarcosine (N-methylglycine). Rapid reaction kinetic studies under anaerobic conditions at pH 8.0 show that the enzyme forms a charge transfer Michaelis complex with sarcosine (E-FAD(ox).sarcosine) that exhibits an intense long-wavelength absorption band (lambda(max) = 516 nm, epsilon(516) = 4800 M(-)(1) cm(-)(1)). Since charge transfer interaction with sarcosine as donor is possible only with the anionic form of the amino acid, the results indicate that the pK(a) of enzyme-bound sarcosine must be considerably lower than the free amino acid (pK(a) = 10.0). No redox intermediate is detectable during sarcosine oxidation, as judged by the isosbestic spectral course observed for conversion of E-FAD(ox).sarcosine to reduced enzyme at 25 or 5 degrees C. The limiting rate of the reductive half-reaction at 25 degrees C (140 +/- 3 s(-)(1)) is slightly faster than turnover (117 +/- 3 s(-)(1)). The kinetics of formation of the Michaelis charge transfer complex can be directly monitored at 5 degrees C where the reduction rate is 4.5-fold slower and complex stability is increased 2-fold. The observed rate of complex formation exhibits a hyperbolic dependence on sarcosine concentration with a finite Y-intercept, consistent with a mechanism involving formation of an initial complex followed by isomerization to yield a more stable complex. Similar results are obtained for charge transfer complex formation with methylthioacetate. The observed kinetics are consistent with structural studies which show that a conformational change occurs upon binding of methylthioacetate and other competitive inhibitors.

Kinetics↗
PubMed1997

Cloning and functional expression of a mammalian gene for a peroxisomal sarcosine oxidase.

Sarcosine oxidation in mammals occurs via a mitochondrial dehydrogenase closely linked to the electron transport chain. An additional H2O2-producing sarcosine oxidase has now been purified from rabbit kidney. A corresponding cDNA was cloned from rabbit liver and the gene designated sox. This rabbit sox gene encodes a protein of 390 amino acids and a molecular mass of 44 kDa identical to the molecular mass estimated for the purified enzyme. Sequence analysis revealed an N-terminal ADP-betaalphabeta-binding fold, a motif highly conserved in tightly bound flavoproteins, and a C-terminal peroxisomal targeting signal 1. Sarcosine oxidase from rabbit liver exhibits high sequence homology (25-28% identity) to monomeric bacterial sarcosine oxidases. Both purified sarcosine oxidase and a recombinant fusion protein synthesized in Escherichia coli contain a covalently bound flavin, metabolize sarcosine, L-pipecolic acid, and L-proline, and cross-react with antibodies raised against L-pipecolic acid oxidase from monkey liver. Subcellular fractionation demonstrated that sarcosine oxidase is a peroxisomal enzyme in rabbit kidney. Transfection of human fibroblast cell lines and CV-1 cells (monkey kidney epithelial cells) with the sox cDNA resulted in a peroxisomal localization of sarcosine oxidase and revealed that the import into the peroxisomes is mediated by the peroxisomal targeting signal 1 pathway.

Amino Acid Sequence↗
PubMed1987

Interaction of tetrahydrofolate and other folate derivatives with bacterial sarcosine oxidase.

Sarcosine oxidase from Corynebacterium sp. P-1 binds 2 mol of tetrahydrofolate/mol of enzyme (KD = 8.8 microM). The same stoichiometry is observed with tetrahydropteroyltetraglutamate (KD = 15.4 microM). Binding is also observed with pteroyltetraglutamate and with 5-formyltetrahydrofolate. In the case of the pteroylmonoglutamates, binding appears to be sensitive to changes in the pteridine ring since no binding is observed with 5-methyltetrahydrofolate or with folate. Sarcosine oxidase can be specifically adsorbed onto an affinity matrix prepared by coupling 5-formyltetrahydrofolate to AH-Sepharose. Tetrahydrofolate does not affect the rate of sarcosine oxidation but does block the formation of formaldehyde as a final product. In the presence of tetrahydrofolate, sarcosine oxidation is accompanied by the formation of 5,10-methylenetetrahydrofolate at a rate that exceeds the rate at which formaldehyde (or a precursor) can be released into solution and which is also considerably faster than the nonenzymic reaction of free formaldehyde with tetrahydrofolate. It is suggested that tetrahydrofolate may serve primarily to trap formaldehyde as it is formed at the active site during sarcosine oxidation. The existence of a catalytically significant binding site for tetrahydrofolate appears to be a general property of sarcosine oxidizing enzymes since similar results have previously been obtained with mammalian sarcosine dehydrogenase, an enzyme that is structurally and mechanistically very different from bacterial sarcosine oxidase.

Aldehyde Oxidoreductases↗
PubMed1965

Origin of the sarcosine molecules of actinomycins.

1. Streptomyces V-187 produces on minimal medium a mixture composed mainly of actinomycin C(1) (actinomycin D) and actinomycin A(1) (actinomycin I). If sarcosine is added to the medium, the micro-organism produces, in addition to actinomycins C(1) and A(1), actinomycin F(8) (actinomycin II) and actinomycin F(9) (actinomycin (III), characterized by the substitution by sarcosine of one or both the proline molecules present in actinomycin C(1). 2. Exogenous sarcosine seems to be incorporated as such by Streptomyces V-187 only in the sarcosine molecule(s) that replace proline in the actinomycins of the F group, whereas, for the synthesis of the other sarcosine molecules, the amino acid is first demethylated to glycine. 3. The incorporation of sarcosine and glycine into actinomycin by Streptomyces antibioticus appears to follow a similar pattern, except that a portion of the methyl group produced in the degradation of sarcosine is utilized as a source of the methyl groups of the antibiotic. This explains the previously reported lack of cross-dilution between glycine and sarcosine observed in the incorporation of these amino acids into actinomycin.

Chromatography, Thin Layer↗
PubMed2005

Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study.

CONTEXT: Agents that enhance N-methyl-D-aspartate (NMDA) function through the glycine modulatory site (D-serine, glycine, or D-cycloserine) or through glycine transporter 1 (sarcosine) improve the symptoms of patients with stable chronic schizophrenia. OBJECTIVE: To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor-enhancing agents have beneficial effects for acute exacerbation of schizophrenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient units of 2 major medical centers in Taiwan. Patients Sixty-five schizophrenic inpatients with acute exacerbation. INTERVENTIONS: Six weeks of treatment with sarcosine (2 g/d), D-serine (2 g/d), or placebo and concomitant optimal risperidone therapy. MAIN OUTCOME MEASURES: Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17 items) total scores. RESULTS: The sarcosine group revealed more reductions in PANSS total scores than the placebo (P = .04) and D-serine (P<.001) groups. Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20 (P = .007) and SANS-17 (P = .003) scores and to D-serine in decreasing SANS-20 (P = .006) and SANS-17 (P = .002) scores. The PANSS-general, PANSS-cognitive, and PANSS-depressive symptoms scores and SANS-alogia and SANS-blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients (P< or =.02 for all). Sarcosine adjunctive therapy also surpassed D-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and PANSS-depressive symptoms scores (P< or =.04 for all). D-serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains. CONCLUSIONS: This first short-term treatment study on NMDA receptor-enhancing agents suggests that sarcosine, superior to D-serine, can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia. This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia, at least during the acute phase. Further studies are needed.

Acute Disease↗