Gene Association: SIRT4
UniProt Search:
SIRT4 (PROTEIN_CODING)
Function Description: sirtuin 4
found 21 associated metabolites with current gene based on the text mining result from the pubmed database.
Nα-Acetyl-L-lysine
N-epsilon-Acetyl-L-lysine also known as Nepsilon-Acetyllysine or N6-Acetyllysine, belongs to the class of organic compounds known as N-acyl-alpha amino acids. N-acyl-alpha amino acids are compounds containing an alpha amino acid which bears an acyl group at one of its nitrogen atoms. N-epsilon-Acetyl-L-lysine can also be classified as an alpha amino acid or a derivatized alpha amino acid. Technically, N-epsilon-Acetyl-L-lysine is a biologically available sidechain, N-capped form of the proteinogenic alpha amino acid L-lysine. Unlike L-lysine, acetylated lysine derivatives such as N-epsilon-Acetyl-L-lysine are zwitterionic compounds. These are molecules that contains an equal number of positively- and negatively-charged functional groups. N-epsilon-Acetyl-L-lysine is found naturally in eukaryotes ranging from yeast to plants to humans. N-acetyl amino acids can be produced either via direct synthesis of specific N-acetyltransferases or via the proteolytic degradation of N-acetylated proteins (often histones) by specific hydrolases. N-epsilon-Acetyl-L-lysine can be biosynthesized from L-lysine and acetyl-CoA via the enzyme known as Lysine N-acetyltransferase. Post-translational lysine-acetylation is one of two major modifications of lysine residues in various proteins – either N-terminal or N-alpha acetylation or N6 (sidechain) acetylation. Side-chain acetylation of specific lysine residues in the N-terminal domains of core histones is a biochemical marker of active genes. Acetylation is now known to play a major role in eukaryotic transcription. Specifically, acetyltransferase enzymes that act on particular lysine side chains of histones and other proteins are intimately involved in transcriptional activation. By modifying chromatin proteins and transcription-related factors, these acetylases are believed to regulate the transcription of many genes. The best-characterized mechanism is acetylation, catalyzed by histone acetyltransferase (HAT) enzymes. HATs function enzymatically by transferring an acetyl group from acetyl-coenzyme A (acetyl-CoA) to the amino group of certain lysine side chains within a histones basic N-terminal tail region. Within a histone octamer, these regions extend out from the associated globular domains, and in the context of a nucleosome, they are believed to bind the DNA through charge interactions (positively charged histone tails associated with negatively charged DNA) or mediate interactions between nucleosomes. Lysine acetylation, which neutralizes part of a tail regions positive charge, is postulated to weaken histone-DNA or nucleosome-nucleosome interactions and/or signal a conformational change, thereby destabilizing nucleosome structure or arrangement and giving other nuclear factors, such as the transcription complex, more access to a genetic locus. In agreement with this is the fact that acetylated chromatin has long been associated with states of transcriptional activation. Specific recognition of N6-acetyl-L-lysine is a conserved function of all bromodomains found in different proteins, recognized as an emerging intracellular signalling mechanism that plays critical roles in regulating gene transcription, cell-cycle progression, apoptosis, DNA repair, and cytoskeletal organization (PMID: 9169194 , 10827952 , 17340003 , 16247734 , 9478947 , 10839822 ). N-acetylated amino acids, such as N-epsilon-Acetyl-L-lysine can be released by an N-acylpeptide hydrolase from histones going through proteolytic degradation (PMID: 16465618). Many N-acetylamino acids are classified as uremic toxins if present in high abundance in the serum or plasma (PMID: 26317986; PMID: 20613759). Uremic toxins are a diverse group of endogenously produced molecules that, if not properly cleared or eliminated by the kidneys, can cause kidney damage, cardiovascular disease and neurological deficits (PMID: 18287557). Isolated from sugarbeet (Beta vulgaris) KEIO_ID A174 Nepsilon-Acetyl-L-lysine is a derivative of the amino acid lysine.
N8-Acetylspermidine
N8-Acetylspermidine is a polyamine. The polyamines, found in virtually all living organisms, are a ubiquitous group of compounds that appear to play a vital role in many cellular processes involving nucleic acids including cell growth and differentiation. The polyamines, found in virtually all living organisms, are a ubiquitous group of compounds that appear to play a vital role in many cellular processes involving nucleic acids including cell growth and differentiation. Acetylation on the terminal nitrogen adjacent to the 4-carbon chain produces N8-acetylspermidine. This reaction is catalyzed by spermidine N8-acetyltransferase and does not result in the conversion of spermidine to putrescine but, instead, the product undergoes deacetylation. This acetyltransferase appears to be associated with chromatin in the cell nucleus and has been reported to be the same as (or related to) the enzyme(s) responsible for histone acetylation. N8-Acetylspermidine does not accumulate in tissues but rather appears to be rapidly deacetylated back to spermidine by a relatively specific cytosolic deacetylase, N8-acetylspermidine deacetylase. The function of this N8-acetylation/deacetylation pathway in cellular processes is not understood clearly, but several observations have suggested a role in cell growth and differentiation. (PMID: 12093478) [HMDB] N8-Acetylspermidine is a polyamine. The polyamines, found in virtually all living organisms, are a ubiquitous group of compounds that appear to play a vital role in many cellular processes involving nucleic acids including cell growth and differentiation. Acetylation on the terminal nitrogen adjacent to the 4-carbon chain produces N8-acetylspermidine. This reaction is catalyzed by spermidine N8-acetyltransferase and does not result in the conversion of spermidine to putrescine. Instead, the product undergoes deacetylation. This acetyltransferase appears to be associated with chromatin in the cell nucleus and has been reported to be the same as (or related to) the enzyme(s) responsible for histone acetylation. N8-Acetylspermidine does not accumulate in tissues but rather appears to be rapidly deacetylated back to spermidine by a relatively specific cytosolic deacetylase, N8-acetylspermidine deacetylase. The function of this N8-acetylation/deacetylation pathway in cellular processes is not understood clearly, but several observations have suggested a role in cell growth and differentiation (PMID: 12093478). KEIO_ID A112
Dimethylbenzimidazole
Dimethylbenzimidazole is an intermediate in Riboflavin metabolism. Dimethylbenzimidazole is the second to last step for the synthesis of alpha-Ribazole. It is converted from Riboflavin then it is converted to N1-(5-Phospho-alpha-D-ribosyl)-5,6-dimethylbenzimidazole via the enzyme nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase (EC 2.4.2.21). Dimethylbenzimidazole is an intermediate in Riboflavin metabolism. KEIO_ID D087 5,6-Dimethyl-1H-benzo[d]imidazole is an endogenous metabolite.
Rhamnetin
Acquisition and generation of the data is financially supported in part by CREST/JST. Rhamnetin is a quercetin derivative found in Coriandrum sativum, inhibits secretory phospholipase A2, with antioxidant and anti-inflammatory activity[1]. Rhamnetin is a quercetin derivative found in Coriandrum sativum, inhibits secretory phospholipase A2, with antioxidant and anti-inflammatory activity[1]. Rhamnetin is a quercetin derivative found in Coriandrum sativum, inhibits secretory phospholipase A2, with antioxidant and anti-inflammatory activity[1].
Nadide
[Spectral] NAD+ (exact mass = 663.10912) and 3,4-Dihydroxy-L-phenylalanine (exact mass = 197.06881) and Cytidine (exact mass = 243.08552) were not completely separated on HPLC under the present analytical conditions as described in AC$XXX. Additionally some of the peaks in this data contains dimers and other unidentified ions. [Spectral] NAD+ (exact mass = 663.10912) and NADP+ (exact mass = 743.07545) were not completely separated on HPLC under the present analytical conditions as described in AC$XXX. Additionally some of the peaks in this data contains dimers and other unidentified ions. COVID info from COVID-19 Disease Map Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS
Paeonol
A polyphenol metabolite detected in biological fluids [PhenolExplorer] Paeonol is an active extraction from the root of Paeonia suffruticosa, Paeonol inhibits MAO-A and MAO-B with IC50 of 54.6 μM and 42.5 μM, respectively. Paeonol is an active extraction from the root of Paeonia suffruticosa, Paeonol inhibits MAO-A and MAO-B with IC50 of 54.6 μM and 42.5 μM, respectively.
3-Methylcrotonyl-CoA
3-Methylcrotonyl-CoA, also known as beta-methylcrotonyl-coenzyme A or dimethylacryloyl-CoA, belongs to the class of organic compounds known as acyl-CoAs. These are organic compounds containing a coenzyme A substructure linked to an acyl chain. Thus, 3-methylcrotonyl-CoA is considered to be a fatty ester lipid molecule. 3-Methylcrotonyl-CoA is a very hydrophobic molecule, practically insoluble (in water), and relatively neutral. 3-Methylcrotonyl-CoA is an essential metabolite for leucine metabolism, is a substrate of 3-methylcrotonyl-CoA carboxylase (EC 6.4.1.4), and is a biotin-dependent mitochondrial enzyme in the catabolism of leucine (OMIM: 609010). 3-Methylcrotonyl-CoA is an essential metabolite for leucine metabolism, a substrate of 3-methylcrotonyl-CoA carboxylase (EC 6.4.1.4), a biotin-dependent mitochondrial enzyme in the catabolism of leucine. (OMIM 609010) [HMDB]. 3-Methylcrotonyl-CoA is found in many foods, some of which are summer savory, lupine, blackcurrant, and soft-necked garlic.
N1-Acetylspermidine
N1-Acetylspermidine is a polyamine. In many organisms, polyamines originate from L-ornithine and methionine. Ornithine decarboxylase (EC 4.1.1.17), a key enzyme in polyamine metabolism, decarboxylates L-ornithine to yield putrescine which is then converted to higher polyamines spermidine and spermine by successive addition of aminopropyl groups derived from decarboxylated S-adenosylmethionine. Aliphatic polyamines occur ubiquitously in organisms and have important functions in the stabilization of cell membranes, biosynthesis of informing molecules, cell growth and differentiation, as well as adaptation to osmotic, ionic, pH and thermal stress. These cationic substances are implicated in multiple functions, therefore it is not surprising that intracellular levels of polyamines are regulated by different mechanisms. The inhibition of polyamine metabolism has important pharmacological and therapeutic implications for the control of physiological processes, reproduction, cancer and parasitic diseases. Recent reports have suggested the idea that parasites with an high turnover of Ornithine Decarboxilase (ODC) are resistant to Difluoromethyl ornithine (DFMO, the irreversible inhibitor of ornithine decarboxylase) because they always contain a fraction of newly synthesized and active enzyme, therefore not DFMO inhibited, sufficient to produce small amounts of putrescine rapidly converted into spermidine, which can support protozoan proliferation. DFMO has proved to be curative in trypanosomiasis, coccidiosis, and certain other protozoan infections. (PMID: 15490259). N1-Acetylspermidine is a polyamine. In many organisms, polyamines originate from L-ornithine and methionine. Ornithine decarboxylase (EC 4.1.1.17), a key enzyme in polyamine metabolism, decarboxylates L-ornithine to yield putrescine which is then converted to higher polyamines spermidine and spermine by successive addition of aminopropyl groups derived from decarboxylated S-adenosylmethionine.
3-Methylglutaconyl-CoA
3-Methylglutaconyl-CoA is a substrate for Methylglutaconyl-CoA hydratase (mitochondrial), Methylcrotonoyl-CoA carboxylase beta chain (mitochondrial) and Methylcrotonoyl-CoA carboxylase alpha chain (mitochondrial). [HMDB]. 3-Methylglutaconyl-CoA is found in many foods, some of which are cocoa bean, evening primrose, winter squash, and rocket salad (sspecies). 3-Methylglutaconyl-CoA is a substrate for Methylglutaconyl-CoA hydratase (mitochondrial), Methylcrotonoyl-CoA carboxylase beta chain (mitochondrial) and Methylcrotonoyl-CoA carboxylase alpha chain (mitochondrial). COVID info from COVID-19 Disease Map Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS
Tiglyl-CoA
Tiglyl-CoA is a metabolite in the degradation of isoleucine to propionic acid pathway. A defect in the conversion of tiglyl-CoA to alpha-methyl-beta-hydroxybutyryl-CoA, results in episodic abdominal pain and acidosis in patients with Tiglic acidemia (OMIM 275190). Tiglyl-CoA is a metabolite in the degradation of isoleucine to propionic acid pathway.
Paeonol
Paeonol is a member of phenols and a member of methoxybenzenes. It has a role as a metabolite. Paeonol is a natural product found in Vincetoxicum paniculatum, Vincetoxicum glaucescens, and other organisms with data available. See also: Paeonia lactiflora root (part of); Paeonia X suffruticosa root (part of). A natural product found in Paeonia rockii subspeciesrockii. Paeonol is an active extraction from the root of Paeonia suffruticosa, Paeonol inhibits MAO-A and MAO-B with IC50 of 54.6 μM and 42.5 μM, respectively. Paeonol is an active extraction from the root of Paeonia suffruticosa, Paeonol inhibits MAO-A and MAO-B with IC50 of 54.6 μM and 42.5 μM, respectively.
Rhamnetin
Rhamnetin is a monomethoxyflavone that is quercetin methylated at position 7. It has a role as a metabolite, an antioxidant and an anti-inflammatory agent. It is a monomethoxyflavone and a tetrahydroxyflavone. It is functionally related to a quercetin. It is a conjugate acid of a rhamnetin-3-olate. Rhamnetin is a natural product found in Ageratina altissima, Ammannia auriculata, and other organisms with data available. A monomethoxyflavone that is quercetin methylated at position 7. 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4h-chromen-4-one, also known as 7-methoxyquercetin or quercetin 7-methyl ether, is a member of the class of compounds known as flavonols. Flavonols are compounds that contain a flavone (2-phenyl-1-benzopyran-4-one) backbone carrying a hydroxyl group at the 3-position. Thus, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4h-chromen-4-one is considered to be a flavonoid lipid molecule. 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4h-chromen-4-one is practically insoluble (in water) and a very weakly acidic compound (based on its pKa). 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4h-chromen-4-one can be found in a number of food items such as tea, apple, sweet orange, and parsley, which makes 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4h-chromen-4-one a potential biomarker for the consumption of these food products. Rhamnetin is a quercetin derivative found in Coriandrum sativum, inhibits secretory phospholipase A2, with antioxidant and anti-inflammatory activity[1]. Rhamnetin is a quercetin derivative found in Coriandrum sativum, inhibits secretory phospholipase A2, with antioxidant and anti-inflammatory activity[1]. Rhamnetin is a quercetin derivative found in Coriandrum sativum, inhibits secretory phospholipase A2, with antioxidant and anti-inflammatory activity[1].
N6-acetyl-L-lysine
An N(6)-acyl-L-lysine where the N(6)-acyl group is specified as acetyl. MS2 deconvoluted using MS2Dec from all ion fragmentation data, MetaboLights identifier MTBLS1040; DTERQYGMUDWYAZ-ZETCQYMHSA-N_STSL_0232_N-epsilon-Acetyl-L-lysine (N6)_8000fmol_190114_S2_LC02MS02_018; Spectrum acquired as described in Naz et al 2017 PMID 28641411. Preparation and submission to MassBank of North America by Chaleckis R. and Tada I. MS2 deconvoluted using CorrDec from all ion fragmentation data, MetaboLights identifier MTBLS1040; Spectrum acquired as described in Naz et al 2017 PMID 28641411. Preparation and submission to MassBank of North America by Chaleckis R. and Tada I. Nepsilon-Acetyl-L-lysine is a derivative of the amino acid lysine.
5,6-Dimethylbenzimidazole
A dimethylbenzimidazole carrying methyl substituents at positions 5 and 6. 5,6-Dimethyl-1H-benzo[d]imidazole is an endogenous metabolite.
CoA 5:1
peonol
Paeonol is an active extraction from the root of Paeonia suffruticosa, Paeonol inhibits MAO-A and MAO-B with IC50 of 54.6 μM and 42.5 μM, respectively. Paeonol is an active extraction from the root of Paeonia suffruticosa, Paeonol inhibits MAO-A and MAO-B with IC50 of 54.6 μM and 42.5 μM, respectively.
NICOTINAMIDE-adenine-dinucleotide
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3-methylbut-2-enoyl-CoA
An unsaturated fatty acyl-CoA that results from the formal condensation of the thiol group of coenzyme A with the carboxy group of 3-methylbut-2-enoic acid.
