MiMeDB: Showing metabocard for 3-Methylhistidine (MMDBc0000349)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2020-12-10 18:35:53 UTC

Update Date

2022-08-31 06:02:31 UTC

Metabolite ID

MMDBc0000349

Metabolite Identification

Common Name

3-Methylhistidine

Description

3-Methylhistidine, also known as 3-MHis, 3MH, pi-methylhistidine or pros-methylhistidine, belongs to the class of organic compounds known as histidine and derivatives. 3MH is also classified as a methylamino acid. Methylamino acids are primarily proteogenic amino acids (found in proteins) which have been methylated (in situ) on their side chains by various methyltransferase enzymes. Histidine can be methylated at either the N1 or N3 position of its imidazole ring, yielding the isomers 1-methylhistidine (1MH; also referred to as tau-methylhistidine, according to IUPAC) or 3-methylhistidine (3MH; pi-methylhistidine, according to IUPAC), respectively. There is considerable confusion with regard to the nomenclature of the methylated nitrogen atoms on the imidazole ring of histidine in histidine-containing proteins (such as actin and myosin) as well as histidine-containing peptides (such as anserine and ophidine/balenine). In particular, older literature (mostly prior to the year 2000) as well as most biochemists and nutrition scientists incorrectly number the imidazole nitrogen atom most proximal to the side chain beta-carbon as 1 or N1, while organic chemists correctly designate it as 3 or N3. As a result, biochemists and nutrition scientists historically designated anserine (Npi-methylated) as beta-alanyl-N1-methylhistidine (or beta-alanyl-1-methylhistidine), whereas according to standard IUPAC nomenclature, anserine is correctly named as beta-alanyl-N3-methylhistidine. As a result, for several decades, many papers incorrectly identified 1MH as a specific marker for dietary consumption or various pathophysiological effects when they really are referring to 3MH – and vice versa (PMID: 24137022 ). To help resolve this issue the IUPAC commission (PMID: 6743224 and IUPAC Compendium of Chemical Terminology, 2nd ed. (the 'Gold Book'). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997)) revised the nomenclature for histidine and introduced the terms pi (for prox or pros – near) and tau (for tele – far) to label the imidazole nitrogens in histidine. Therefore, the pi nitrogen is the nitrogen closest to the side chain beta carbon (atom #3 or N3) while the tau nitrogen is most distant from the side chain beta carbon (atom #1 or N1). IUPAC’s goal is for the global community to refer to the molecule depicted here is as “pi-methylhistidine” with the hope that the archaic term, 3-methylhistidine will eventually disappear. Unfortunately, this has not happened and confusion still persists. Older versions of the HMDB (prior to 2022) as well as current versions of some databases, such as PubChem, KEGG, and UniProt, indicate that an acceptable synonym for 3MH is tau-methylhistidine or otherwise somehow equate 1MH and 3MH. This is incorrect and it continues to sow confusion. Indeed, a key paper that identified METTL9 as the enzyme responsible for pi-methylation of histidine in most vertebrates also incorrectly labeled the METTL9 product as 1MH (PMID: 33563959 ). Similarly, a key paper that identified METTL18 as the enzyme responsible for tau-methylation of histidine incorrectly labelled the METTL18 product as 3MH (PMID: 33693809 ). Likewise, many members of the biochemical/nutrition community still incorrectly refer to 1MH as pi-methlyhistidine and 3MH as tau-methylhistidine. This has led to even more confusion. To maintain consistency for this compound description, all papers cited herein that incorrectly refer to 3MH as 1MH and vice versa, will have their conclusions re-stated and the citation will be marked with the phrase “3MH/1MH switch”. 3MH is a free amino acid arising from the proteolysis of 3MH-containing proteins and peptides. It is not synthesized on its own, nor can it be incorporated into proteins as an amino acid. However, it can be incorporated into certain dipeptides through the action of the enzyme known as carnosine synthase I. 3MH can only be generated from histidine residues through the action of methyltransferases as a protein post-translational modification event. Histidine methylation on the 3- or pi site of histidine-containing proteins is mediated by only one known enzyme – METTL9. Recent discoveries have shown that 3MH is produced in essentially all vertebrates via the methyltransferase enzyme known as METTL9 (3MH/1MH switch - PMID: 33563959 ). METTL9 is a broad-specificity S-adenosylmethionine-mediated methyltransferase that mediates the formation of the majority of 3MH present in mammalian and other vertebrate proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where 'x' is a small amino acid consisting of A, N, G, S, or T. This H[ANGST]H or HxH motif is found in a number of abundant mammalian proteins such as ARMC6, S100A9, and NDUFB3 (3MH/1MH switch - PMID: 33563959 ). In addition to these pi-His-methylated proteins, a specialized dipeptide called anserine (called beta-alanyl-3-methyl-L-histidine) that consists of beta-alanine and 3MH is also known and particularly well studied (PMID: 24137022 ). This methylated analog of carnosine, which is naturally produced in the liver via the enzyme carnosine synthase I (PMID: 20097752 ), is especially abundant in the skeletal muscles and brains of mammals, birds, and fish (PMID: 24137022 ). Anserine, like its homologs ophidine and carnosine, is believed to act as a pH buffer (for lactic acid generated by muscles), an antiglycating agent, and an antioxidant. Neither ophidine nor anserine are produced in humans, with humans being the only vertebrate not producing (or producing very little) methylated histidine versions of carnosine (PMID: 24137022 ). Because of its abundance in some muscle-related proteins but especially because of the high abundance of anserine found in poultry and fish, 3MH has been found to be a good biomarker for the consumption of meat (PMID: 21527577 ). Dietary studies have shown that general poultry consumption (p-trend = 0.0006) and especially chicken consumption (p-trend = 0.0003) are associated with increased levels of 3MH in human plasma (PMID: 30018457 ). The consumption of fish, especially salmon and cod, has also been shown to increase the levels of 3MH in serum and urine (3MH/1MH switch PMID: 31401679 ). As a general rule, urinary 3MH is associated with white meat intake (p< 0.001), whereas urinary 1MH is associated with red meat intake (p< 0.001) (3MH/1MH switch - PMID: 34091671 ).

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

HEADER    PROTEIN                                 15-OCT-19   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   15-OCT-19         0                                  
HETATM    1  C   UNK     0      -1.651   1.651   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0       1.060   3.620   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0       2.306   1.175   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0       0.290  -0.290   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0       1.060   2.080   0.000  0.00  0.00           C+0
HETATM    6  C   UNK     0      -0.274   4.390   0.000  0.00  0.00           C+0
HETATM    7  C   UNK     0      -0.274   5.930   0.000  0.00  0.00           C+0
HETATM    8  N   UNK     0      -1.608   3.620   0.000  0.00  0.00           N+0
HETATM    9  N   UNK     0       1.830  -0.290   0.000  0.00  0.00           N+0
HETATM   10  N   UNK     0      -0.186   1.175   0.000  0.00  0.00           N+0
HETATM   11  O   UNK     0      -1.608   6.700   0.000  0.00  0.00           O+0
HETATM   12  O   UNK     0       1.060   6.700   0.000  0.00  0.00           O+0
HETATM   13  H   UNK     0       1.060   5.160   0.000  0.00  0.00           H+0
CONECT    1   10                                                            
CONECT    2    5    6                                                       
CONECT    3    5    9                                                       
CONECT    4    9   10                                                       
CONECT    5    2    3   10                                                  
CONECT    6    2    7    8   13                                             
CONECT    7    6   11   12                                                  
CONECT    8    6                                                            
CONECT    9    3    4                                                       
CONECT   10    1    4    5                                                  
CONECT   11    7                                                            
CONECT   12    7                                                            
CONECT   13    6                                                            
MASTER        0    0    0    0    0    0    0    0   13    0   26    0
END

Synonyms

Value	Source
(2S)-2-Amino-3-(1-methyl-1H-imidazol-5-yl)propanoic acid	ChEBI
3-Methyl-L-histidine	ChEBI
N-pros-Methyl-L-histidine	ChEBI
(2S)-2-Amino-3-(1-methyl-1H-imidazol-5-yl)propanoate	Generator
3-N-Methyl-L-histidine	HMDB
L-3-Methylhistidine	HMDB
N(pros)-Methyl-L-histidine	HMDB
N3-Methyl-L-histidine	HMDB
3-Methylhistidine hydride	HMDB
3-Methylhistidine dihydrochloride	HMDB
3-Methylhistidine	ChEBI
Pi methylhistidine	HMDB
N(Pi)-methylhistidine	HMDB
N Pi-methylhistidine	HMDB

Molecular Formula

C₇H₁₁N₃O₂

Average Mass

169.1811

Monoisotopic Mass

169.085126611

IUPAC Name

(2S)-2-amino-3-(1-methyl-1H-imidazol-5-yl)propanoic acid

Traditional Name

3,methylhistidine

CAS Registry Number

Not Available

SMILES

[H][C@](N)(CC1=CN=CN1C)C(O)=O

InChI Identifier

InChI=1S/C7H11N3O2/c1-10-4-9-3-5(10)2-6(8)7(11)12/h3-4,6H,2,8H2,1H3,(H,11,12)/t6-/m0/s1

InChI Key

JDHILDINMRGULE-LURJTMIESA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as histidine and derivatives. Histidine and derivatives are compounds containing cysteine or a derivative thereof resulting from reaction of cysteine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Histidine and derivatives

Alternative Parents

Substituents

Histidine or derivatives
Alpha-amino acid
L-alpha-amino acid
Imidazolyl carboxylic acid derivative
Aralkylamine
N-substituted imidazole
Azole
Imidazole
Heteroaromatic compound
Amino acid
Carboxylic acid
Azacycle
Organoheterocyclic compound
Monocarboxylic acid or derivatives
Organic nitrogen compound
Organonitrogen compound
Organooxygen compound
Primary amine
Primary aliphatic amine
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Carbonyl group
Organic oxygen compound
Amine
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

non-proteinogenic L-alpha-amino acid (CHEBI:27596 )
L-histidine derivative (CHEBI:27596 )

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

Predicted Properties

Property	Value	Source
Water Solubility	6.93 g/L	ALOGPS
logP	-2.9	ALOGPS
logP	-3.4	ChemAxon
logS	-1.4	ALOGPS
pKa (Strongest Acidic)	1.96	ChemAxon
pKa (Strongest Basic)	9.43	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	81.14 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	42.96 m³·mol⁻¹	ChemAxon
Polarizability	16.58 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00dm-9500000000-ab7d6324146b8775fe50	2016-09-22	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-00fr-9400000000-42443c78fdfca9db1926	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-11-05	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negative	splash10-014i-0900000000-3cbd02f5b6c4e6e64eb9	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT , negative	splash10-0udi-0900000000-e6ce7548fd6f09e2098f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , negative	splash10-014i-0900000000-3cbd02f5b6c4e6e64eb9	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-014i-2900000000-77f55ec21b9e637c0148	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-014i-0900000000-25e42ab3c1bd0832a7fe	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-0ab9-3900000000-fb4a45b41e8cb903c156	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-014i-0900000000-0a98679ff9db2f56925a	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-014i-1900000000-7b29b213a49dfa3c0f7d	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-00di-0900000000-5a4990ec47e6292c0f7f	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-014i-0900000000-993e2b71358969de5168	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Negative	splash10-00di-9500000000-1817d9d8adbfaf0595f9	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Negative	splash10-014i-9100000000-2e05be86f146c22455ce	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-014i-2900000000-15f0e43eb0d06e7f3ef3	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-0002-9200000000-5a1ab4d052e6ba4a76e4	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-0002-9000000000-c1951c88c84885804fb6	2012-07-24	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-00di-0900000000-4e0fea0fe9b1142db07b	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-0592-4900000000-ee1bce969d650e9fcfbe	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-0002-9200000000-1ad733cdcfa4db4fe3b9	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-0002-9000000000-a87ff5cc0642ea3af69c	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-0002-9000000000-28a73708493f968c2ac6	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positive	splash10-0002-9800000000-6565ccf96757ef3bc08f	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-00di-0900000000-2d351351f285b2188710	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0592-4900000000-ee1bce969d650e9fcfbe	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0002-9200000000-1ad733cdcfa4db4fe3b9	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0002-9000000000-2ed34e7b458d9f8c092f	2017-09-14	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 125 MHz, H₂O, experimental)		2012-12-04	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, H₂O, experimental)		2012-12-04	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)		2021-09-29	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, H₂O, experimental)		2021-10-10	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)		2012-12-05	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm

Biospecimen Locations

Blood
Cerebrospinal Fluid (CSF)
Feces
Saliva
Skeletal Muscle
Urine

Tissue Locations

Skeletal Muscle

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0192131	Beta-Ala-His dipeptidase	Unknown	Q96KN2	Homo sapiens
MMDBp0195610	Carnosine synthase 1	Unknown	A5YM72	Homo sapiens
MMDBp0196837	HemK methyltransferase family member 1	Unknown	Q9Y5R4
MMDBp0196881	Methyltransferase-like protein 2B	Unknown	Q6P1Q9
MMDBp0196882	Methyltransferase-like protein 6	Unknown	Q8TCB7
MMDBp0197020	Uncharacterized methyltransferase WBSCR22	Unknown	O43709
MMDBp0197076	Histidine protein methyltransferase 1 homolog	Enzyme	O95568	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reaction ID	Precursor	Product	Enzyme	Reaction Type	Data Source	Reference
MMDBr0005721	S-Adenosylmethionine	3-Methylhistidine	Not Available	Formation of Methyl-Histidine	VMH	30371894
MMDBr0005752	3-Methylhistidine	3-Methylhistidine	Not Available	Transport of Methyl-Histidine by System N Transport	VMH	30371894
MMDBr0005753	3-Methylhistidine	3-Methylhistidine	Not Available	Transport of Methyl-Histidine by System L Transport (Lat1)	VMH	30371894
MMDBr0005754	3-Methylhistidine	3-Methylhistidine	Not Available	Transport of Methyl-Histidine by System L Transport (Lat2)	VMH	30371894

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference
Alzheimer's disease	Slight Decrease	Association	Human Cerebrospinal Fluid (CSF)	HMDB	17031479
Alzheimer's disease	Increased	Association	Human Urine	HMDB	17031479
Alzheimer's disease		Association	Human Blood	HMDB	17031479
Diabetes mellitus type 2	Slight Decrease	Association	Human Urine	HMDB	15899597
Kidney disease	Slight Increase	Association	Human Blood	HMDB	10838467
Obesity	Slight Decrease	Association	Human Urine	HMDB	15899597
Propionic acidemia	Increased	Association	Human Urine	HMDB	19551947
Eosinophilic esophagitis		Association	Human Urine	HMDB	Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria	Bacteroidetes	1	Human stool; Human feces	Indirect association between microbiota composition and metabolites measured in host biospecimen
Bacteria	Firmicutes	4	Human ; Human feces; Human stool	Indirect association between microbiota composition and metabolites measured in host biospecimen
Eukaryota/Fungi	Ascomycota	1	Human feces; Human saliva	Unknown

Exposure Sources

Source Type	Source Sub-type	Species	Data Source	Reference

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified									HMDB
Human Cerebrospinal fluid (csf)	Detected and Quantified	2.48	1.58			uM	Adult (>18 years old)	Not Specified	Alzheimer's disease	HMDB	17031479
Human Urine	Detected and Quantified	24.0	1.7			umol/mmol creatinine	Adult (>18 years old)	Both	Alzheimer's disease	HMDB	17031479
Human Blood	Detected and Quantified	5.16	1.27			uM	Elderly (>65 years old)	Both	Alzheimer's disease	HMDB	17031479
Human Urine	Detected and Quantified	11.6	6.6			umol/mmol creatinine	Adult (>18 years old)	Not Specified	Diabetes mellitus	HMDB	15899597
Human Blood	Detected and Quantified	50.7	12.9			uM	Adult (>18 years old)	Female	Early preeclampsia	HMDB	22494326
Human Blood	Detected and Quantified	13.0	10.4			uM	Adult (>18 years old)	Both	Kidney disease	HMDB	10838467
Human Blood	Detected and Quantified	23.7	18.6			uM	Adult (>18 years old)	Both	Kidney disease	HMDB	10838467
Human Urine	Detected and Quantified	16.0	9.0			umol/mmol creatinine	Adult (>18 years old)	Not Specified	Obesity	HMDB	15899597
Human Blood	Detected and Quantified	50.0	14.6			uM	Adult (>18 years old)	Female	Pregnancy	HMDB	22494326
Human Urine	Detected and Quantified	44.5	1.3			umol/mmol creatinine	Adult (>18 years old)	Both	Propionic acidemia	HMDB	19551947
Human Urine	Detected and Quantified	5.26				umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	19309105
Human Urine	Detected and Quantified	12.5	4.2			umol/mmol creatinine	Adult (>18 years old)	Not Specified	Normal	HMDB	15899597
Human Urine	Detected and Quantified	13.556	2.487			umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	11052553
Human Urine	Detected and Quantified	15.806	5.404			umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	11052553
Human Urine	Detected and Quantified	16.0206	4.895			umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	11052553
Human Urine	Detected and Quantified	16.5		2.8	59.8	umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	24023812
Human Urine	Detected and Quantified	17.0268	1.572			umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	11052553
Human Urine	Detected and Quantified	17.705	6.00349			umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	11052553
Human Urine	Detected and Quantified	17.977	5.902			umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	11052553
Human Urine	Detected and Quantified	18.191	7.0323			umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	11052553
Human Urine	Detected and Quantified	18.203	6.512			umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	11052553
Human Blood	Detected and Quantified	3.0		2.7	5.9	uM	Adult (>18 years old)	Not Specified	Normal	HMDB	4017235
Human Cerebrospinal fluid (csf)	Detected and Quantified	3.82	2.43			uM	Adult (>18 years old)	Not Specified	Normal	HMDB	17031479
Human Urine	Detected and Quantified	32.79	20.35			umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	HMDB	19468821
Human Urine	Detected and Quantified	39.57	15.83			umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	HMDB	19468821
Human Urine	Detected and Quantified	39.57	23.74			umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	HMDB	19468821
Human Urine	Detected and Quantified	42.76	22.84			umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	HMDB	2026685
Human Urine	Detected and Quantified			5.4	35	umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	27012787
Human Urine	Detected and Quantified			5.8	50	umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	27012787
Human Urine	Detected and Quantified	57.778	73.153			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Eosinophilic esophagitis	HMDB	Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Human Blood	Detected and Quantified	2.7		0.0	5.9	uM	Adult (>18 years old)	Both	Normal	HMDB	Alan Wu, Tietz Clinical Guide to Laboratory Tests.
Human Urine	Detected and Quantified	44.944	41.318			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	HMDB	Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Human Urine	Detected and Quantified	69.27				umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	Shaykhutdinov RA, MacInnis GD, Dowlatabadi R, Weljie AM, Vogel HJ. Quantitative analysis of metabolite concentrations in human urine samples using 13C{1H} NMR spectroscopy. Metabolomics. 2009
Human Saliva	Detected and Quantified	0.00950	0.0494			uM	Adult (>18 years old)	Male	Normal	HMDB	Sugimoto et al. (2013) Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles.
Human Saliva	Detected and Quantified	0.0982	0.128			uM	Adult (>18 years old)	Female	Normal	HMDB	Sugimoto et al. (2013) Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles.
Human Saliva	Detected and Quantified	0.126	0.139			uM	Adult (>18 years old)	Female	Normal	HMDB	Sugimoto et al. (2013) Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles.
Human Saliva	Detected and Quantified	0.134	0.110			uM	Adult (>18 years old)	Female	Normal	HMDB	Sugimoto et al. (2013) Physiological and environmental parameters associated with mass spectrometry-based salivary metabolomic profiles.
Human Saliva	Detected and Quantified	27.68	28.12			uM	Adult (>18 years old)	Both	Normal	HMDB	Zerihun T. Dame, Farid Aziat, Rupasri Mandal, Ram Krishnamurthy, Souhaila Bouatra, Shima Borzouie, An Chi Guo, Tanvir Sajed, Lu Deng, Hong Lin, Philip Liu, Edison Dong, David S. Wishart "The human saliva metabolome" Metabolomics (2015) DOI 10.1007/s11306-015-0840-5
Human Urine	Detected and Quantified			5.32	29.64	umol/mmol creatinine	Adolescent (13-18 years old)	Not Specified	Normal	HMDB	Mayo Clinic (https://neurology.testcatalog.org/show/AAPD)
Human Urine	Detected and Quantified			6.33	35.75	umol/mmol creatinine	Children (1-13 years old)	Not Specified	Normal	HMDB	Mayo Clinic (https://neurology.testcatalog.org/show/AAPD)
Human Urine	Detected and Quantified			7.92	27.83	umol/mmol creatinine	Adult (>18 years old)	Not Specified	Normal	HMDB	Mayo Clinic (https://neurology.testcatalog.org/show/AAPD)
Human Urine	Detected and Quantified			8.71	29.41	umol/mmol creatinine	Children (1-13 years old)	Not Specified	Normal	HMDB	Mayo Clinic (https://neurology.testcatalog.org/show/AAPD)
Human Urine	Detected and Quantified			9.73	37.33	umol/mmol creatinine	Children (1-13 years old)	Not Specified	Normal	HMDB	Mayo Clinic (https://neurology.testcatalog.org/show/AAPD)
Human Urine	Detected and Quantified			9.95	39.59	umol/mmol creatinine	Infant (0-1 year old)	Not Specified	Normal	HMDB	Mayo Clinic (https://neurology.testcatalog.org/show/AAPD)
Human Skeletal muscle	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	24023812
Human Feces	Detected but not Quantified						Not Specified	Both	Normal	HMDB	25486321
Human Urine	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	17022649
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	21736852
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	23269817
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	27543620
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	25037050
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	29808030
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057

External Links

HMDB ID

HMDB0000479

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

FDB093613

KNApSAcK ID

Not Available

Chemspider ID

58494

KEGG Compound ID

C01152

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

3-Methylhistidine

METLIN ID

5466

PubChem Compound

64969

PDB ID

Not Available

ChEBI ID

27596

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

Young VR, Munro HN: Ntau-methylhistidine (3-methylhistidine) and muscle protein turnover: an overview. Fed Proc. 1978 Jul;37(9):2291-300. [PubMed:350635 ]
Tomas FM, Ballard FJ, Pope LM: Age-dependent changes in the rate of myofibrillar protein degradation in humans as assessed by 3-methylhistidine and creatinine excretion. Clin Sci (Lond). 1979 Apr;56(4):341-6. doi: 10.1042/cs0560341. [PubMed:477219 ]
McKeran RO, Halliday D, Purkiss P: Comparison of human myofibrillar protein catabolic rate derived from 3-methylhistidine excretion with synthetic rate from muscle biopsies during L-[alpha-15N]lysine infusion. Clin Sci Mol Med. 1978 May;54(5):471-5. doi: 10.1042/cs0540471. [PubMed:750147 ]
Teahon K, Rideout JM: A sensitive and specific high performance liquid chromatographic assay for imidazole dipeptides and 3-methylhistidine in human muscle biopsies, serum and urine. Biomed Chromatogr. 1992 Jan-Feb;6(1):16-9. doi: 10.1002/bmc.1130060106. [PubMed:1600369 ]
Sjolin J, Stjernstrom H, Henneberg S, Hambraeus L, Friman G: Evaluation of urinary 3-methylhistidine excretion in infection by measurements of 1-methylhistidine and the creatinine ratios. Am J Clin Nutr. 1989 Jan;49(1):62-70. doi: 10.1093/ajcn/49.1.62. [PubMed:2912013 ]
Adlerberth A, Jagenburg R, Lindstedt G, Stenstrom G, Hasselgren PO: Effects of thyroid hormone and beta-adrenoceptor blocking agents on urinary excretion of 3-methylhistidine and plasma amino acids in man. Eur J Clin Invest. 1986 Aug;16(4):316-20. doi: 10.1111/j.1365-2362.1986.tb01348.x. [PubMed:3093243 ]
Long CL, Dillard DR, Bodzin JH, Geiger JW, Blakemore WS: Validity of 3-methylhistidine excretion as an indicator of skeletal muscle protein breakdown in humans. Metabolism. 1988 Sep;37(9):844-9. doi: 10.1016/0026-0495(88)90118-7. [PubMed:3138511 ]
Lamisse F, May MA, Couet C, Constans T, Bacq Y, Delarue J, Lamagnere JP, Colombat P, Garrigue MA: [Changes in nutritional status at the initial phase of treatment of cancers and malignant hemopathies]. Rev Med Interne. 1987 May-Jun;8(3):257-61. doi: 10.1016/s0248-8663(87)80228-x. [PubMed:3616232 ]
Bucciante G, Mencini A, Boninsegna A, Branca D, Scutari A, Scutari G: 3-Methylhistidine urinary excretion as an index of skeletal muscle protein metabolism: reference values. G Clin Med. 1985 Nov-Dec;66(11-12):451-8. [PubMed:3835089 ]
Buchholz-Wimmer GB, Wimmer W, Herbertz L, Reinauer H: [3-Methylhistidine as a parameter for the determination of muscle proteolysis in the post-stress syndrome and in diabetes mellitus]. Infusionsther Klin Ernahr. 1984 Jun;11(3):168-74. [PubMed:6434416 ]
Schmitz JE: [Effect of metabolism-oriented substrate administration on energy and protein metabolism in polytraumatized artificial respiration patients]. Infusionsther Klin Ernahr. 1984 Aug;11(4):205-18. [PubMed:6434422 ]
Neuhauser M, Bergstrom J, Chao L, Holmstrom J, Nordlund L, Vinnars E, Furst P: Urinary excretion of 3-methylhistidine as an index of muscle protein catabolism in postoperative trauma: the effect of parenteral nutrition. Metabolism. 1980 Dec;29(12):1206-13. doi: 10.1016/0026-0495(80)90147-x. [PubMed:6779092 ]
Elia M, Carter A, Bacon S, Winearls CG, Smith R: Clinical usefulness of urinary 3-methylhistidine excretion in indicating muscle protein breakdown. Br Med J (Clin Res Ed). 1981 Jan 31;282(6261):351-4. doi: 10.1136/bmj.282.6261.351. [PubMed:6780020 ]
Lunyong VE, Friedman Z: Myofibrillar protein degradation in premature infants with respiratory distress as assessed by 3-methylhistidine and creatinine excretions. Am J Clin Nutr. 1982 Sep;36(3):485-91. doi: 10.1093/ajcn/36.3.485. [PubMed:7113954 ]
Emery PW, Rennie MJ: Elimination by formaldehyde of interference with 3-methylhistidine determination: application of the method to the study of muscle protein degradation. Anal Biochem. 1982 Oct;126(1):67-73. doi: 10.1016/0003-2697(82)90109-9. [PubMed:7181118 ]
Rathmacher JA, Flakoll PJ, Nissen SL: A compartmental model of 3-methylhistidine metabolism in humans. Am J Physiol. 1995 Jul;269(1 Pt 1):E193-8. doi: 10.1152/ajpendo.1995.269.1.E193. [PubMed:7631776 ]
Wang Z, Deurenberg P, Matthews DE, Heymsfield SB: Urinary 3-methylhistidine excretion: association with total body skeletal muscle mass by computerized axial tomography. JPEN J Parenter Enteral Nutr. 1998 Mar-Apr;22(2):82-6. doi: 10.1177/014860719802200282. [PubMed:9527964 ]
Nygren J, Thorell A, Brismar K, Essen P, Wernerman J, McNurlan MA, Garlick PJ, Ljungqvist O: Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged. Clin Sci (Lond). 2002 Apr;102(4):457-64. doi: 10.1042/cs1020457. [PubMed:11914108 ]
Vesali RF, Klaude M, Thunblad L, Rooyackers OE, Wernerman J: Contractile protein breakdown in human leg skeletal muscle as estimated by [2H3]-3-methylhistidine: a new method. Metabolism. 2004 Aug;53(8):1076-80. doi: 10.1016/j.metabol.2004.02.017. [PubMed:15281022 ]
Chinkes DL: Methods for measuring tissue protein breakdown rate in vivo. Curr Opin Clin Nutr Metab Care. 2005 Sep;8(5):534-7. doi: 10.1097/01.mco.0000170754.25372.37. [PubMed:16079625 ]
Bird SP, Tarpenning KM, Marino FE: Independent and combined effects of liquid carbohydrate/essential amino acid ingestion on hormonal and muscular adaptations following resistance training in untrained men. Eur J Appl Physiol. 2006 May;97(2):225-38. doi: 10.1007/s00421-005-0127-z. Epub 2006 Mar 24. [PubMed:16456674 ]
Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]
Boldyrev AA, Aldini G, Derave W: Physiology and pathophysiology of carnosine. Physiol Rev. 2013 Oct;93(4):1803-45. doi: 10.1152/physrev.00039.2012. [PubMed:24137022 ]
Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]
Holecek M: Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement. Nutrients. 2020 Mar 22;12(3). pii: nu12030848. doi: 10.3390/nu12030848. [PubMed:32235743 ]
Said MY, Rodriguez-Nino A, Post A, Schutten JC, Kieneker LM, Gomes-Neto AW, van Londen M, Oste MC, Borgonjen-van den Berg KJ, Nolte IM, van den Berg E, de Blaauw P, van der Krogt J, Heiner-Fokkema MR, Navis G, Yard BA, Bakker SJ: Meat intake and risk of mortality and graft failure in kidney transplant recipients. Am J Clin Nutr. 2021 Oct 4;114(4):1505-1517. doi: 10.1093/ajcn/nqab185. [PubMed:34091671 ]

Showing metabocard for 3-Methylhistidine (MMDBc0000349)

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