Glutaric acid: A product of tryptophan metabolism

Gholson, R.K.; Sanders, Donald C.; Henderson, L.M.

doi:10.1016/0006-291x(59)90071-3

Cited by 26 publications

(7 citation statements)

References 7 publications

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“…Interestingly, the increase of glutaric acid in feces was also observed in humans consuming red wine rich in polyphenols [31]. Since tryptophan and lysine have been identified as the precursors of glutaric acid in bacterial metabolism [55,56], whether the increase of glutaric acid in the current study was associated with altered microbial metabolism of amino acids or other specific metabolic pathways requires further studies.…”

Section: Discussionmentioning

confidence: 64%

Inhibitory Effects of Green Tea Polyphenols on Microbial Metabolism of Aromatic Amino Acids in Humans Revealed by Metabolomic Analysis

et al. 2019

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The bioactivities and potential health benefits of green tea polyphenols (GTP) have been extensively investigated, but the metabolic impact of chronic GTP intake on humans is not well defined. In this study, fecal and urine samples from postmenopausal female subjects taking a GTP supplement or placebo for 12 months were compared by liquid chromatography-mass spectrometry-based metabolomic analysis. The GTP-derived and GTP-responsive metabolites were identified and characterized by structural elucidation and quantitative analysis of the metabolites contributing to the separation of control and treatment samples in the multivariate models. Major GTP and their direct sulfate and glucuronide metabolites were absent in feces and urine. In contrast, GTP-derived phenyl-γ-valerlactone and phenylvaleric acid metabolites were identified as the most abundant GTP-derived metabolites in feces and urine, suggesting extensive microbial biotransformation of GTP in humans. Interestingly, GTP decreased the levels of microbial metabolites of aromatic amino acids (AAA), including indoxyl sulfate, phenylacetylglutamine, and hippuric acid, in urine. However, it did not affect the levels of AAA, as well as other microbial metabolites, including short-chain fatty acids and secondary bile acids, in feces. 16S rRNA gene sequencing indicated that the fecal microbiome was not significantly affected by chronic consumption of GTP. Overall, microbial metabolism is responsible for the formation of GTP metabolites while GTP metabolism may inhibit the formation of AAA metabolites from microbial metabolism. Because these GTP-derived and GTP-responsive metabolites have diverse bioactivities, microbial metabolism of GTP and AAA may play important roles in the beneficial health effects of green tea consumption in humans.

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Section: Discussionmentioning

confidence: 64%

Inhibitory Effects of Green Tea Polyphenols on Microbial Metabolism of Aromatic Amino Acids in Humans Revealed by Metabolomic Analysis

et al. 2019

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“…Glutarate, in its coenzyme A (CoA) form, is an intermediate of both tryptophan and lysine catabolism (Borsook et al ., 1948; Gholson et al ., 1959) (Figure 2A). Glutaryl-CoA can either be further broken down to crotonyl-CoA by the enzyme glutaryl-CoA dehydrogenase (GCDH), or form glutarate (Figure 2A) (Dwyer et al ., 2000).…”

Section: Resultsmentioning

confidence: 99%

Glutarate regulates T cell function and metabolism

Minogue

Cunha

Quaranta

et al. 2022

Preprint

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T cell function is influenced by several metabolites; some acting through enzymatic inhibition of α-KG-dependent dioxygenases (αKGDDs), others, through post-translational modification of lysines in important targets. We show here that glutarate, a product of amino acid catabolism, has the capacity to do both, with effects on T cell function and differentiation. Glutarate exerts those effects through αKGDD inhibition and through direct regulation of T cell metabolism via post-translational modification of the pyruvate dehydrogenase E2 subunit. Diethyl-glutarate, a cell-permeable form of glutarate, alters CD8+T cell differentiation and increases cytotoxicity against target cells.In vivoadministration of the compound reduces tumor growth and is correlated with increased levels of both peripheral and intratumoral cytotoxic CD8+T cells. These results demonstrate that glutarate regulates both T cell metabolism and differentiation, with a potential role in the improvement of T cell immunotherapy.

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“…Of the 1-tryptophane entering the blood stream, a certain proportion will be incorporated into tissue proteins. In adults in nitrogen balance, about 1% of the residue (Udenfriend, Weissbach and Sjoerdsma, 1956) is metabolized via serotonin to 5-hydroxyindoleacetic acid, a further small amount is excreted directly as tryptophane and the greater part of the lemainder is broken down to 3-hydroxyanthranilic acid and then via glutarate and acetate to CO2 (Gholson, Sanders and Henderson, 1959 to nicotinic acid appearing in the urine as N1methylnicotinamide and N-methyl-2-pyridone-5carboxamide.…”

Section: Discussionmentioning

confidence: 99%

The Abnormality of Tryptophane Metabolism in Children with Mongolism

OʼBrien¹,

Groshek²

1962

Archives of Disease in Childhood

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There is evidence (Gershoff, Hegsted and Trulson, 1958; Jer6me, Lejeune and Turpin, 1960;O'Brien, Groshek and Streamer, 1960) that children with mongolism have a defect in tryptophane metabolism which is characterized primarily by a diminished urinary excretion of xanthurenic acid.The purpose of this study was to confirm this observation using more exact techniques and to attempt to specify the alteration in metabolism more precisely by comparing the effects of 1-tryptophane loading on the urinary excretion coefficients (,umols/ kg./7 hours) of both 5-hydroxy-3-indoleacetic acid and the kynurenine pathway metabolites of tryptophane in a group of children with mongolism and in a control group of non-mongoloid mentally retarded children.Methods Twenty-one children with mongolism, aged 9 to 16 years, and 19 non-mongoloid mental defectives of comparable age, sex and intelligence were studied. All the children were active, able to feed themselves and keep themselves clean. Both groups were in the same institution and received an identical diet. At the commencement of the test, fasting subjects voided and then drank 300 ml. of flavoured milk in which was suspended 100 ml./kg. body weight of 1-tryptophane. All urine was collected for seven hours after the tryptophane load, and, to ensure completeness, individual voidings were supervised by one or other of the investigators. This seven-hour collection period was chosen as being the longest period that could be properly monitored.A measured aliquot of urine was assayed for 5-hydroxy-3-indoleacetic acid (Udenfriend, Titus and Weissbach, 1955), N'-methylnicotinamide (Huff and Perlzweig, 1947;Asami, 1957), and 4-pyridoxic acid (Reddy, Reynolds and Price, 1958). Other metabolites of the kynurenine pathway were separated by two-dimensional paper chromatography and identified under ultraviolet light. These were then eluted and estimated either directly by their absorbance in the ultraviolet, or as azo compounds coupled with pyridine or naphthylethylenediamine (Coppini, Benassi and Montorsi, 1959;O'Brien and Ibbott, 1962a). The chromatographic methods were linear within the experimental range and recoveries for kynurenine, acetylkynurenine, kynurenic acid, hydroxykynurenine, xanthurenic acid and hydroxyanthranilic acid gave a mean value of 97-6% (82-5-104-7%) with a mean coefficient of variation of 7 9% (4-6-12 6%). Reproducibility, expressed also as a coefficient of variation, averaged 4-7% for standards and 5 9% for urine samples. These figures were shown to be slightly, but not significantly, better than those for column chromatography techniques (Satoh and Price, 1958) in the cases of kynurenic and xanthurenic acids.Because intravenous tryptophane loading was not permitted, fasting, one-and two-hour serum samples were obtained for estimation of the tryptophane levels. These were determined as the enol-borate complex after adsorption and elution from a Dowex 50 column (O'Brien and lbbott, 1962b).

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Glutaric acid: A product of tryptophan metabolism

Cited by 26 publications

References 7 publications

Inhibitory Effects of Green Tea Polyphenols on Microbial Metabolism of Aromatic Amino Acids in Humans Revealed by Metabolomic Analysis

Inhibitory Effects of Green Tea Polyphenols on Microbial Metabolism of Aromatic Amino Acids in Humans Revealed by Metabolomic Analysis

Glutarate regulates T cell function and metabolism

The Abnormality of Tryptophane Metabolism in Children with Mongolism

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