Lac-Phe

Last updated
Lac-Phe
Lac-Phe.svg
Names
IUPAC name
(2S)-2-[[(2S)-2-hydroxypropanoyl]amino]-3-phenylpropanoic acid
Other names
N-[(S)-lactoyl]-L-phenylalaninate
N-Lactoyl-phenylalanine
N-Lactoylphenylalanine
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
PubChem CID
  • InChI=1S/C12H15NO4/c1-8(14)11(15)13-10(12(16)17)7-9-5-3-2-4-6-9/h2-6,8,10,14H,7H2,1H3,(H,13,15)(H,16,17)/t8-,10-/m0/s1
    Key: IIRJJZHHNGABMQ-WPRPVWTQSA-N
  • C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)O
Properties
C12H15NO4
Molar mass 237.255 g·mol−1
Related compounds
Related N-acyl-alpha-amino acids
 N-Acetylaspartic acid
N-acetylcysteine
N-Acetylglutamic acid
N-Acetylglutamine
N-Acetylleucine
N-formylmethionine
Related compounds
 Lactamide
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Lactoylphenylalanine, or Lac-Phe, is an N-lactoyl-amino acid metabolite produced by mammals and microorganisms [1] [2] [3] [4] [5] . In humans, levels are increased by intense exercise and in the inborn error of metabolism phenylketonuria. [6] [7] [8] [1] [9] In mice, high levels of Lac-Phe in the blood cause a decrease of food intake [6] and in humans, its production has been shown to correlate with adipose tissue loss during an endurance exercise intervention. [10] In mammals it is created from (S)-lactate and L-phenylalanine by the cytosol nonspecific dipeptidase (CNDP2) protein. [1] It is classified as N-acyl-alpha-amino acid and pseudodipeptide. [11]

Contents

It has also been reported that as an additive, N-L-lactoyl phenylalanine improves the taste of food, conferring an umami flavor [12] . It is found naturally in significant amounts in some traditional Chinese fermented foods such as preserved pickles and soy sauce [13] , and in Parmigiano-Reggiano cheese [14] . Oral intake of Lac-Phe does not have anti-obesity effects in mice, though intraperitoneal injection does reduce food intake and weight gain. [6] Activity dependent cell labeling indicates Lac-Phe activated neural populations in the hypothalamus and brainstem. [15]

See also

Related Research Articles

<span class="mw-page-title-main">Amino acid</span> Organic compounds containing amine and carboxylic groups

Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 appear in the genetic code of life.

<span class="mw-page-title-main">Phenylketonuria</span> Amino acid metabolic disorder

Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.

<span class="mw-page-title-main">Tyrosine</span> Amino acid

L-Tyrosine or tyrosine or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is from the Greek tyrós, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine. It is encoded by the codons UAC and UAU in messenger RNA.

<span class="mw-page-title-main">Phenylalanine</span> Type of α-amino acid

Phenylalanine is an essential α-amino acid with the formula C
9H
11NO
2. It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino acid is classified as neutral, and nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The L-isomer is used to biochemically form proteins coded for by DNA. Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and the biological pigment melanin. It is encoded by the messenger RNA codons UUU and UUC.

<span class="mw-page-title-main">Phenylalanine hydroxylase</span> Mammalian protein found in Homo sapiens

Phenylalanine hydroxylase (PAH) (EC 1.14.16.1) is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PAH is one of three members of the biopterin-dependent aromatic amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin (BH4, a pteridine cofactor) and a non-heme iron for catalysis. During the reaction, molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate. In humans, mutations in its encoding gene, PAH, can lead to the metabolic disorder phenylketonuria.

<span class="mw-page-title-main">Aminoacyl tRNA synthetase</span> Class of enzymes

An aminoacyl-tRNA synthetase, also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA. It does so by catalyzing the transesterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code.

<span class="mw-page-title-main">Branched-chain amino acid</span> Amino acid with a branched carbon chain

A branched-chain amino acid (BCAA) is an amino acid having an aliphatic side-chain with a branch. Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid and alloisoleucine.

<span class="mw-page-title-main">Aminoacyl-tRNA</span> Molecule that delivers the amino acid to the ribosome during translation

Aminoacyl-tRNA is tRNA to which its cognate amino acid is chemically bonded (charged). The aa-tRNA, along with particular elongation factors, deliver the amino acid to the ribosome for incorporation into the polypeptide chain that is being produced during translation.

<span class="mw-page-title-main">Aromatic amino acid</span> Amino acid having an aromatic ring

An aromatic amino acid is an amino acid that includes an aromatic ring.

The discovery of an orally inactive peptide from snake venom established the important role of angiotensin converting enzyme (ACE) inhibitors in regulating blood pressure. This led to the development of captopril, the first ACE inhibitor. When the adverse effects of captopril became apparent new derivates were designed. Then after the discovery of two active sites of ACE: N-domain and C-domain, the development of domain-specific ACE inhibitors began.

In enzymology, a leucine—tRNA ligase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Phenylalanine—tRNA ligase</span> Protein domain

In enzymology, a phenylalanine—tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, an aminoacylase (EC 3.5.1.14) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">ACOT11</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 11 also known as StAR-related lipid transfer protein 14 (STARD14) is an enzyme that in humans is encoded by the ACOT11 gene. This gene encodes a protein with acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates which relies on its StAR-related lipid transfer domain. Expression of a similar murine protein in brown adipose tissue is induced by cold exposure and repressed by warmth. Expression of the mouse protein has been associated with obesity, with higher expression found in obesity-resistant mice compared with obesity-prone mice. Alternative splicing results in two transcript variants encoding different isoforms.

<span class="mw-page-title-main">FARS2</span> Protein-coding gene in the species Homo sapiens

Phenylalanyl-tRNA synthetase, mitochondrial (FARS2) is an enzyme that in humans is encoded by the FARS2 gene. This protein encoded by FARS2 localizes to the mitochondrion and plays a role in mitochondrial protein translation. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 14, also known as Alpers encephalopathy, as well as spastic paraplegia 77 and infantile-onset epilepsy and cytochrome c oxidase deficiency.

<span class="mw-page-title-main">Cytosol nonspecific dipeptidase</span>

Cytosolic non-specific dipeptidase also known as carnosine dipeptidase 2 is an enzyme that in humans is encoded by the CNDP2 gene. This enzyme catalyses the hydrolysis of dipeptides, preferentially those containing hydrophobic amino acids. The human enzyme uses manganese ions as a cofactor. In addition to its function as a peptidase, the enzyme also functions to generate N-lactoyl amino acids, such as N-lactoyl-phenylalanine, via the process of "reverse proteolysis". A similar pathway conjugates amino acids to Beta-hydroxybutyric acid.

<i>N</i>-Acylamides Class of endogenous fatty acid compounds

N-acyl amides are a general class of endogenous fatty acid compounds characterized by a fatty acyl group linked to a primary amine metabolite by an amide bond. Broadly speaking, N-acyl amides fall into several categories: amino acid conjugates, neurotransmitter conjugates, ethanolamine conjugates, and taurine conjugates. N-acyl amides have pleiotropic signaling functions in physiology, including in cardiovascular function, metabolic homeostasis, memory, cognition, pain, motor control and others. Initial attention focused on N-acyl amides present in mammalian organisms, however recently lipid signaling systems consisting of N-acyl amides have also been found to be present in invertebrates, such as Drosophila melanogaster. N-acyl amides play important roles in many biochemical pathways involved in a variety of physiological and pathological processes, as well as the metabolic enzymes, transporters, and receptors that regulate their signaling.

Brian Selby Hartley FRS was a British biochemist. He was Professor of Biochemistry at Imperial College London from 1974 to 1991.

Andrimid is an antibiotic natural product that is produced by the marine bacterium Vibrio coralliilyticus. Andrimid is an inhibitor of fatty acid biosynthesis by blocking the carboxyl transfer reaction of acetyl-CoA carboxylase (ACC).

α-Methylphenylalanine Monoamine metabolism inhibitor

α-Methylphenylalanine is an artificial amino acid and a phenethylamine and amphetamine derivative. It is the α-methylated analogue of phenylalanine, the precursor of the catecholamine neurotransmitters, and the amino acid analogue of amphetamine (α-methylphenethylamine), a psychostimulant and monoamine releasing agent.

References

  1. 1 2 3 Jansen RS, Addie R, Merkx R, Fish A, Mahakena S, Bleijerveld OB, et al. (May 2015). "N-lactoyl-amino acids are ubiquitous metabolites that originate from CNDP2-mediated reverse proteolysis of lactate and amino acids". Proceedings of the National Academy of Sciences of the United States of America. 112 (21): 6601–6606. Bibcode:2015PNAS..112.6601J. doi: 10.1073/pnas.1424638112 . PMC   4450436 . PMID   25964343.
  2. ↑ Sgarbi, Elisa; Lazzi, Camilla; Iacopino, Luca; Bottesini, Chiara; Lambertini, Francesca; Sforza, Stefano; Gatti, Monica (2013-09-01). "Microbial origin of non proteolytic aminoacyl derivatives in long ripened cheeses". Food Microbiology. 35 (2): 116–120. doi:10.1016/j.fm.2013.02.013. ISSN   0740-0020.
  3. ↑ Bottesini, Chiara; Tedeschi, Tullia; Dossena, Arnaldo; Sforza, Stefano (2014-02-01). "Enzymatic production and degradation of cheese-derived non-proteolytic aminoacyl derivatives". Amino Acids. 46 (2): 441–447. doi:10.1007/s00726-013-1637-3. ISSN   1438-2199.
  4. ↑ Feng, Junwei; Huang, Zikun; Huang, Mingtao; Cui, Chun; Zhao, Mouming; Feng, Yunzi (2024-11-30). "Revealing the Microbial Origins of N-Lactoyl Amino Acids in Soy Sauce: Synthesis Conditions, Potential Enzymes, and Utilization Preference". Journal of Agricultural and Food Chemistry. doi:10.1021/acs.jafc.4c04907. ISSN   0021-8561.
  5. ↑ Xiao, Shuke; Li, Veronica L.; Long, Jonathan Z. (2024-08-01). "Lac-Phe (N-lactoyl-phenylalanine)". Trends in Endocrinology & Metabolism. 35 (8): 758–759. doi: 10.1016/j.tem.2024.05.007 . ISSN   1043-2760. PMID   39137723.
  6. 1 2 3 Li VL, He Y, Contrepois K, Liu H, Kim JT, Wiggenhorn AL, et al. (June 2022). "An exercise-inducible metabolite that suppresses feeding and obesity". Nature. 606 (7915): 785–790. Bibcode:2022Natur.606..785L. doi:10.1038/s41586-022-04828-5. PMC   9767481 . PMID   35705806. S2CID   249710767.
  7. ↑ Wong C (15 June 2022). "Appetite-suppressing molecule helps obese mice lose weight". New Scientist. Retrieved 18 June 2022.
  8. ↑ Reynolds G (15 June 2022). "Why Does a Hard Workout Make You Less Hungry?". The New York Times. Retrieved 18 June 2022.
  9. ↑ Václavík, Jan; Coene, Karlien L. M.; Vrobel, Ivo; Najdekr, Lukáš; Friedecký, David; Karlíková, Radana; Mádrová, Lucie; Petsalo, Aleksanteri; Engelke, Udo F. H.; van Wegberg, Annemiek; Kluijtmans, Leo A. J.; Adam, Tomáš; Wevers, Ron A. (2018). "Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra". Journal of Inherited Metabolic Disease. 41 (3): 407–414. doi:10.1007/s10545-017-0109-4. ISSN   1573-2665.
  10. ↑ Hoene M, Zhao X, Machann J, Birkenfeld AL, Heni M, Peter A, et al. (January 2023). "Exercise-Induced N-Lactoylphenylalanine Predicts Adipose Tissue Loss during Endurance Training in Overweight and Obese Humans". Metabolites. 13 (1): 15. doi: 10.3390/metabo13010015 . PMC   9863672 . PMID   36676940. S2CID   255077184.
  11. ↑ "Metabocard for N-Lactoylphenylalanine". The Human Metabolome Database (HMDB). The Metabolomics Innovation Centre (TIMC). HMDB0062175.
  12. ↑ Feng, Junwei; Huang, Zikun; Cui, Chun; Zhao, Mouming; Feng, Yunzi (2024-10-01). "Synthesis, taste characteristics and taste mechanism of N-lactoyl leucine from soy sauce using sensory analysis and UPLC-MS/MS". Food Chemistry. 454: 139670. doi:10.1016/j.foodchem.2024.139670. ISSN   0308-8146.
  13. ↑ Wu J, Gao J, Lin J, Cui C, Li L, He S, Brennan C (May 2022). "Preparation and Taste Characteristics of Kokumi N-Lactoyl Phenylalanine in the Presence of Phenylalanine and Lactate". Journal of Agricultural and Food Chemistry. 70 (17): 5396–5407. doi:10.1021/acs.jafc.2c00530. PMID   35452224. S2CID   248345604.
  14. ↑ Sforza, Stefano; Cavatorta, Valeria; Galaverna, Gianni; Dossena, Arnaldo; Marchelli, Rosangela (2009-10-01). "Accumulation of non-proteolytic aminoacyl derivatives in Parmigiano-Reggiano cheese during ripening". International Dairy Journal. 19 (10): 582–587. doi:10.1016/j.idairyj.2009.04.009. ISSN   0958-6946.
  15. ↑ Moya-Garzon MD, Wang M, Li VL, Lyu X, Wei W, Tung AS; et al. (2024). "A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites". Cell. doi: 10.1016/j.cell.2024.10.032 . PMID   39536746.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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