Degradation Of Biogenic Amines Research Articles

Biogenic Amines Degradation by Lactobacillus plantarum: Toward a Potential Application in Wine

Biogenic amines (BA) in wine represent a toxicological risk for the health of the consumer, with several trade implications. In this study 26 strains of Lactobacillus plantarum were analyzed for their ability to degrade BA commonly found during wine fermentation. Two strains of L. plantarum were selected in reason of their ability to degrade putrescine and tyramine. The degradation was assessed in vitro, both in presence of the BA and in presence of the specific chemical precursor and of producer bacteria. The two L. plantarum biotypes were found capable to work synergically. In addition, the survival in wine-like medium and the aptitude to degrade malic acid after alcoholic fermentation of the selected L. plantarum strains was analyzed. Our results suggest the potential application of wine L. plantarum strains to design malolactic starter cultures able to degrade BA in wine.

Potential of wine-associated lactic acid bacteria to degrade biogenic amines

Some lactic acid bacteria (LAB) isolated from fermented foods have been proven to degrade biogenic amines through the production of amine oxidase enzymes. Since little is known about this in relation to wine micro-organisms, this work examined the ability of LAB strains (n=85) isolated from wines and other related enological sources, as well as commercial malolactic starter cultures (n=3) and type strains (n=2), to degrade histamine, tyramine and putrescine. The biogenic amine-degrading ability of the strains was evaluated by RP-HPLC in culture media and wine malolactic fermentation laboratory experiments. Although at different extent, 25% of the LAB isolates were able to degrade histamine, 18% tyramine and 18% putrescine, whereas none of the commercial malolactic starter cultures or type strains were able to degrade any of the tested amines. The greatest biogenic amine-degrading ability was exhibited by 9 strains belonging to the Lactobacillus and Pediococcus groups, and most of them were able to simultaneously degrade at least two of the three studied biogenic amines. Further experiments with one of the strains that showed high biogenic amine-degrading ability (L. casei IFI-CA 52) revealed that cell-free extracts maintained this ability in comparison to the cell suspensions at pH 4.6, indicating that amine-degrading enzymes were effectively extracted from the cells and their action was optimal in the degradation of biogenic amines. In addition, it was confirmed that wine components such as ethanol (12%) and polyphenols (75 mg/L), and wine additives such as SO(2) (30 mg/L), reduced the histamine-degrading ability of L. casei IFI-CA 52 at pH 4.6 by 80%, 85% and 11%, respectively, in cell suspensions, whereas the reduction was 91%, 67% and 50%, respectively, in cell-free extracts. In spite of this adverse influence of the wine matrix, our results proved the potential of wine-associated LAB as a promising strategy to reduce biogenic amines in wine.

THE ACIDOGENIC METABOLISM OF LACTOBACILLUS PLANTARUM CRL 681 IMPROVES SARCOPLASMIC PROTEIN HYDROLYSIS DURING MEAT FERMENTATION

ABSTRACT The hydrolysis of sarcoplasmic proteins during the growth of Lactobacillus plantarum CRL 681 isolated from fermented sausage was evaluated. Fermentation was carried out in a meat model system under controlled pH conditions (pH 4.0 and 6.0) at 30C for 96 h. The ability of this strain to grow and degrade soluble meat proteins at both assayed pHs was demonstrated. Results showed that sarcoplasmic protein hydrolysis at pH 4.0, as occurring during sausage fermentation, can be attributed to the combined action of acidic meat endogenous proteases, L. plantarum CRL 681 proteolytic activity and acid‐induced changes arising from the bacterial fermentative metabolism. On the other hand, bacterial proteolysis was mainly involved on the hydrolytic changes observed at pH 6.0.PRACTICAL APPLICATIONS Lactobacillus plantarum CRL 681 isolated from Argentinean sausages showed to display technological metabolic traits such as high acidification rate, proteolytic and peptidase activity, biogenic amines degradation and absence of amino acid decarboxylase activity which can beneficially affect the quality and safety of fermented sausages. In addition, from the results of this study, L. plantarum CRL 681 acidogenic metabolism not only would assure hygienic quality of fermented sausages but would increase free amino acids and peptides release from meat proteins. As a whole, this strain has the potential to be successfully used as starter culture to improve final product quality.

국내 참치 부산물 내 히스타민 생성 주요 세균의 특성 구명

Biogenic amines은 발효제품과 같이 어류 속의 미생물에서 분비된 decarboxylase의 free amino acid의 decarboxylation에 의해 형성된다. 본 연구는 국내 어분 제조원료로 이용되고 있는 참치 부산물의 항영양인자로 작용하는 biogenic amines (histamine, tyramine, tryptamine, putrescine, cadaverine)의 분해조절을 위해 참치 부산물의 특성 구명을 위한 연구로 실시하였다. 참치 부산물의 pH 및 염도 농도는 6.51과 3.35%이었으며, 참치 어분의 pH 및 염도 농도는 5.58과 5.83% 이었다. 참치 부산물 내 존재하고 있는 균주 및 주요 미생물을 확인한 결과 Total bacteria, aerobic plate count (APC), Total coliform (TC), Lactobacillus spp. 및 Bacillus spp.는 각각 9.20, 9.29, 5.67, 7.82 및 7.58(Log CFU/g)이었다. 참치 부산물 내 히스타민 주요 생성균을 확인하기 위해 TLC 방법을 이용하였으며 히스타민 선택배지에서 추출한 미생물 중 총 7종의 히스타민 생성 균주를 선발하였다. 선발된 균주는 HPLC 분석을 통하여 히스타민 농도를 측정하여 아민 생성 미생물을 재확인하였다. Trypicase soy broth에 1% L-histidine (TSBH)을 첨가한 배지에서 분리한 7종의 히스타민 생성 균주를 16SrRNA 염기서열 분석 방법을 통해 분석한 결과, 참치 부산물내 주요 우점 아민 생성 미생물은 L. lactis subsp. lactis, K.pneummonlae, L. garvieae, V. olivaceus, H. alvei, L. garvieae 및 Morganella morganii가 주요 균주로 분석되었다. 16S rRNA 분석결과로 만들어진 phylogenetic tree는 다른 계통임을 보여주며 이는 biogenic amine을 생성하는 그람 양성 및 음성균으로 분류될 수 있다. Biogenic amines are generally formed through the decarboxylation of specific free amino acids by exogenous decarboxylases released by microbial species associated with the fish products and fermented feeds. This study was conducted to investigate the properties of e tuna waste regarding the control of degradation of biogenic amines (histamine, tyramine, tryptamine, putrescine, and cadaverine) that might be related with the anti-nutritional factor of the tuna waste that is used for manufacturing domestic fish meal. The values of pH and the salt content were 6.51, 3.35% in tuna waste and 5.58 and 5.83% in tuna fish meal, respectively. The strains and dominant bacteria tested in the tuna waste sample were 9.20, 9.29, 5.67, 7.82 and 7.58 log CFU/g of total bacteria, aerobic plate count (APC), total coliform (TC), Lactobacillus spp. and Bacillus spp., respectively. The main histamine forming-bacteria (HFB) in tuna waste were detected by silica gel thin-layer chromatography (TLC) and 7 histamine-forming bacterial species were isolated among microbes grown in selective medium. The histamine concentration was determined by detection of fluorescence of ο-phthaldialdehyde (OPA) derivatives using HPLC and the date were used to reconfirm the identities of the amine-producing bacteria. The 15 histamine- forming bacteria strains grown in trypicase soy broth (TSB) supplemented with 1% L-histidine (TSBH) were identified as Lactococcus(L.) lactis subsp. lactis, Klebsiella pneummonlae, L. garvieae 36, Vibrio olivaceus, Hafnia alvei and L. garvieae which were main dominant amine - producing strains, and Morganella morganii identified by 16S ribosomal RNA (rRNA) sequencing with PCR amplification. A Phylogenetic tree generated from the 16S rRNA sequencing data showed different phyletic lines that could be readily classified as biogenic amine forming gram-positive and negative bacteria.

MAO-A-induced mitogenic signaling is mediated by reactive oxygen species, MMP-2, and the sphingolipid pathway

The degradation of biogenic amines by monoamine oxidase A (MAO-A) generates reactive oxygen species (ROS) which participate in serotonin and tyramine signaling. This study aimed to investigate the role of ROS in the mitogenic signaling activated during tyramine and serotonin oxidation by MAO-A in smooth muscle cells (SMC). Incubation of SMC with serotonin or tyramine induced intracellular ROS generation, and a signaling cascade involving metalloproteases and the neutral sphingomyelinase-2 (nSMase2, the initial step of the sphingolipid pathway), ERK1/2 phosphorylation, and DNA synthesis. Silencing MAO-A by siRNA, pharmacological MAO-A inhibitors (pargyline and Ro41-1049), and the antioxidant/ROS scavenger butylated hydroxytoluene (BHT) inhibited the signaling cascade, suggesting that ROS generated during tyramine oxidation by MAO-A are required. The MMP inhibitor Batimastat, MMP2-specific siRNA, and MMP2 deletion (MMP2 −/− fibroblasts) blocked nSMase activation and SMC proliferation, suggesting a role for MMP2 in this signaling pathway. Silencing nSMase2 by siRNA did not inhibit ROS generation and MMP2 activation, but blocked SMC proliferation induced by tyramine, suggesting that nSMase2 is downstream MMP2. These findings demonstrate that H 2O 2-generated during tyramine oxidation by MAO-A triggers a stress-induced mitogenic signaling via the MMP2/sphingolipid pathway, which could participate in excessive remodeling and alteration of the vascular wall.

Association Study of a Monoamine Oxidase A Gene Promoter Polymorphism with Major Depressive Disorder and Antidepressant Response

Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of biogenic amines, may be implicated in the pathogenesis of major depressive disorder (MDD) and be related to the therapeutic effects of antidepressants. To elucidate a genetic predisposition of MDD, we studied a variable-number-tandem-repeat (VNTR) polymorphism in the promoter region of the MAOA gene in a Chinese population of 230 MDD patients and 217 controls. We also examined the association of this polymorphism and antidepressant therapeutic response in the MDD patients who underwent a 4-week fluoxetine treatment. Our results showed a significantly increased frequency of 4-repeat (4R) allele in MDD patients, especially in the female population. Furthermore, MDD female patients who were 3R homozygotes had a significantly better response to 4-week fluoxetine treatment when compared to 4R carriers (p=0.024), but there was a nonsignificant difference found in male patients (p=0.081). Since the 4R allele transcribed 2-10 times more efficiently than those with 3R allele, our findings suggest that the MAOA-uVNTR may be involved in the pathogenesis of MDD and the antidepressant therapeutic mechanisms in Chinese population, and that there may be a gender effect in this association.

Tyramine degradation and tyramine/histamine production by lactic acid bacteria and Kocuria strains

Of 53 strains of lactic acid bacteria and Kocuria, screened for production or degradation of biogenic amines, 29 Kocuria varians and four strains of Enterococcusfaecalisproduced tyramine and, at lower concentrations, histamine. In contrast, Lactobacillus strains that did not possess amino acid decarboxylase activity degraded tyramine. The greatest tyramine oxidase activity was present in the strains L. casei CRL705 (98% degradation) and CRL678 (93%) as well as in L. plantarum CRL681 (69%) and CRL682 (60%).

Analysis of the monoamine oxidase A (MAOA) gene in bipolar affective disorder by association studies, meta-analyses, and sequencing of the promoter

Monoamine oxidases catalyse the oxidative degradation of biogenic amines including neurotransmitters such as noradrenaline, dopamine, and 5-hydroxytryptamine (5-HT). Three groups have reported positive associations of the monoamine oxidase A (MAOA) gene with bipolar affective disorder although other studies have been negative. In an extension of a previous study [Rubinsztein et al., 1996: Human Molec Genet 5:779-782] we report association studies of MAOA polymorphic markers and affective disorders. The polymorphisms comprised a CA-repeat microsatellite in intron 2 and a Fnu4HI G/T silent polymorphism at position 941 of the cDNA sequence. No significant differences were found when the control allele frequencies were compared with those in bipolar, unipolar, or combined bipolar + unipolar groups. Meta-analyses were then performed to include the data of all published studies using the MAOA microsatellite and Fnu4HI polymorphisms. Separate meta-analyses were performed for Caucasian and Japanese studies, as allele frequencies of the microsatellite in these populations were markedly different. Associations of bipolar affective disorder in pooled male and female groups were found with the MAOA microsatellite in both the Caucasian (P < 0.02) and the Japanese (P < 0.02) meta-analyses. In view of these positive associations, and as previous results have shown that coding variants do not account for the normal population variation in MAOA activity, over 1,300 bp of the promoter were sequenced in 22 bipolar cases and 1 control. A novel polymorphic promoter variable number of tandem repeats (VNTR) located approximately 1,200 bp upstream from the translation start site was demonstrated. However, there was no association of this promoter VNTR with affective disorder. These results suggest that there may be functional variants in other regions of the MAOA gene or neighbouring genes that affect bipolar affective disorder risk.

Analysis of the monoamine oxidase A (MAOA) gene in bipolar affective disorder by association studies, meta‐analyses, and sequencing of the promoter

Monoamine oxidases catalyse the oxidative degradation of biogenic amines including neurotransmitters such as noradrenaline, dopamine, and 5-hydroxytryptamine (5-HT). Three groups have reported positive associations of the monoamine oxidase A (MAOA) gene with bipolar affective disorder although other studies have been negative. In an extension of a previous study [Rubinsztein et al., 1996: Human Molec Genet 5:779–782] we report association studies of MAOA polymorphic markers and affective disorders. The polymorphisms comprised a CA-repeat microsatellite in intron 2 and a Fnu4HI G/T silent polymorphism at position 941 of the cDNA sequence. No significant differences were found when the control allele frequencies were compared with those in bipolar, unipolar, or combined bipolar + unipolar groups. Meta-analyses were then performed to include the data of all published studies using the MAOA microsatellite and Fnu4HI polymorphisms. Separate meta-analyses were performed for Caucasian and Japanese studies, as allele frequencies of the microsatellite in these populations were markedly different. Associations of bipolar affective disorder in pooled male and female groups were found with the MAOA microsatellite in both the Caucasian (P < 0.02) and the Japanese (P < 0.02) meta-analyses. In view of these positive associations, and as previous results have shown that coding variants do not account for the normal population variation in MAOA activity, over 1,300 bp of the promoter were sequenced in 22 bipolar cases and 1 control. A novel polymorphic promoter variable number of tandem repeats (VNTR) located approximately 1,200 bp upstream from the translation start site was demonstrated. However, there was no association of this promoter VNTR with affective disorder. These results suggest that there may be functional variants in other regions of the MAOA gene or neighbouring genes that affect bipolar affective disorder risk. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:398–406, 1999. © 1999 Wiley-Liss, Inc.

Structure of the human gene for monoamine oxidase type A

Monoamine oxidases, type A and type B, are principal enzymes for the degradation of biogenic amines, including catecholamines and serotonin. These isozymes have been implicated in neuropsychiatric disorders. Previously, cDNA clones for both MAO-A and MAO-B have been sequenced and the genes encoding them have been localized to human chromosome Xp11.23-Xp11.4. In this work, we isolated human genomic clones spanning almost all the MAOA gene from cosmid and phage libraries using a cDNA probe for MAO-A. Restriction mapping and sequencing show that the human MAOA gene extends over 70 kb and is composed of 15 exons. The exon structure of human MAOA is similar to that described by others for human MAOB. Exon 12 (bearing the codon for cysteine, which carries the covalently bound FAD cofactor) and exon 13 are highly conserved between human MAOA and MAOB genes (92% at the amino acid level). Earlier work revealed two species of MAO-A mRNA, 2.1 kb and 4.5-5.5 kb. We now report on further cDNA isolation and sequencing, which demonstrates that the longer message has an extension of 2.2 kb in the 3' noncoding region. This extended region is contained entirely within exon 15. The two messages therefore appear to be generated by the use of two alternative polyadenylation sites. Results from the present work should facilitate the mutational analysis of functional domains of MAO-A and MAO-B. Knowledge of the gene structure will also help in evaluating the role of genetic variations in MAO-A in human disease through the use of genomic DNA, which is more accessible than the RNA, as a template for PCR-amplification and sequencing.

Synthesis, Function, and Degradation of Catecholamine Neurotransmitters

Publisher Summary This chapter discusses some of the recent findings on the function and regulation of neurotransmitters. The chapter focuses on the intracellular synthesis and degradation of biogenic amines. A few specific examples illustrate the growing knowledge of the role of neurotransmitter-synthesizing and -degrading enzymes in disease processes. Neurotransmitter synthesizing and degrading enzymes play crucial roles in neuronal activity and normal physiological function by contributing to regulation of neurotransmitter levels. They also are important determinants in pathological conditions, as exemplified by the deficiency of dihydropteridine reductase (DHPR) in phenylketonuria variants and by the MAO B-catalyzed activation of a neurotoxin that causes Parkinson's disease in humans and primates. DHPR deficiency appears to be a typical genetic disorder, in which a missing enzyme leads to aberrations in the brain metabolism, although the precise nature of these abnormalities has not yet been identified. MAOs contribution to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-toxicity is particularly intriguing because the disease symptoms result from the interaction of an environmentally derived chemical with a genetically controlled amine-degrading enzyme.

Immunological uniqueness of human monoamine oxidases A and B: new evidence from studies with monoclonal antibodies to human monoamine oxidase A

Monoamine oxidase (EC 1.4.3.4; MAO) is the primary enzyme responsible for the intraneuronal degradation of biogenic amines in the central nervous system. An understanding of the physiological significance of the functional and regulatory differences between the two forms of the enzyme, MAOs A and B, would be facilitated by the availability of antibodies specific for the two forms of the enzyme. We previously isolated and characterized a monoclonal antibody (MAO B-1C2, previously designated MAO-1C2) which binds human MAO B but not A. We describe here four new monoclonal antibodies (designated MAO A-3C9, A-4F10, A-7B10, and A-7E10) which were elicited to highly purified MAO A from human placenta and which, in the presence of antimouse IgG and Staphylococcus aureus, immunoprecipitate greater than 90% of the catalytically active purified MAO A. MAO A-3C9 appears to have a lower affinity for purified MAO A than the other three antibodies and does not immunoprecipitate either MAO A or MAO B from human platelets or from Triton X-100 extracts of human placental and liver mitochondria. MAO A-4F10, A-7B10, and A-7E10 immunoprecipitate catalytically active MAO A from Triton X-100 extracts of human placental and liver mitochondria, but not catalytically active MAO B from either pletelets or from Triton X-100 extracts of human liver mitochondria. Collectively, these anti-MAO monoclonal antibodies reveal unique epitopes on human MAO A not shared by MAO B, and at least one epitope on MAO B not shared by MAO A. These immunochemical differences support the hypothesis that MAO A and MAO B are different proteins, presumably isozymes.

Effects of tricyclic antidepressants on platelet monoamine oxidase activity.

The eight subjects in this study were diagnosed as having primary or secondary depression and were treated with amitriptyline, 100 to 300 mg/day. Activity of platelet monoamine oxidase (MAO), an enzyme responsible for the degradation of biogenic amines, was determined before and after treatment with amitriptyline. Pretreatment values for MAO activity ranged from 17.94 to 44.89 U. After amitriptyline the values ranged from 0.66 to 41.94 U, a mean decrease of 50.2%. These results are consistent with the hypothesis that the tricyclic antidepressants act, at least in part, by inhibition of MAO.

Is kernicterus due to inhibition of brain hexose-monophosphate shunt activity by bilirubin?

Degradation of biogenic amines in the central nervous system is accomplished by the monoamine oxidase system. The by-products of this reaction, hydrogen peroxide and amino aldehydes, are toxic to neurones. Detoxification of these by-products is normally mediated by generation of NADPH via the hexosemono-phosphate (HMP) shunt. It is proposed that inhibition of the HMP shunt by unconjugated bilirubin leads to the toxic accumulation of hydrogen peroxide and aldehydes.