# Threonine aldolase

Last updated
threonine aldolase
Identifiers
EC number 4.1.2.5
CAS number 62213-23-4
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures
Gene Ontology
threonine aldolase 1 pseudogene
Identifiers
SymbolTHA1P
NCBI gene 390816
HGNC 18004
RefSeq XM_372682
Other data
Locus Chr. 17 q25.3

In enzymology, a threonine aldolase (EC 4.1.2.5) is an enzyme that catalyzes the chemical reaction

The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme.

Catalysis is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst, which is not consumed in the catalyzed reaction and can continue to act repeatedly. Because of this, only very small amounts of catalyst are required to alter the reaction rate in principle.

A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking of chemical bonds between atoms, with no change to the nuclei, and can often be described by a chemical equation. Nuclear chemistry is a sub-discipline of chemistry that involves the chemical reactions of unstable and radioactive elements where both electronic and nuclear changes can occur.

## Contents

L-threonine ${\displaystyle \rightleftharpoons }$ glycine + acetaldehyde

Hence, this enzyme has one substrate, L-threonine, and two products, glycine and acetaldehyde.

Products are the species formed from chemical reactions. During a chemical reaction reactants are transformed into products after passing through a high energy transition state. This process results in the consumption of the reactants. It can be a spontaneous reaction or mediated by catalysts which lower the energy of the transition state, and by solvents which provide the chemical environment necessary for the reaction to take place. When represented in chemical equations products are by convention drawn on the right-hand side, even in the case of reversible reactions. The properties of products such as their energies help determine several characteristics of a chemical reaction such as whether the reaction is exergonic or endergonic. Additionally the properties of a product can make it easier to extract and purify following a chemical reaction, especially if the product has a different state of matter than the reactants. Reactants are molecular materials used to create chemical reactions. The atoms aren't created or destroyed. The materials are reactive and reactants are rearranging during a chemical reaction. Here is an example of reactants: CH4 + O2. A non-example is CO2 + H2O or "energy".

Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest amino acid (since carbamic acid is unstable), with the chemical formula NH2CH2‐COOH. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is integral to the formation of alpha-helices in secondary protein structure due to its compact form. For the same reason, it is most abundant amino acid in collagen triple-helices. Glycine is also an inhibitory neurotransmitter - interference with its release within the spinal cord (such as during a Clostridium tetani infection) can cause spastic paralysis due to uninhibited muscle contraction.

Acetaldehyde (systematic name ethanal) is an organic chemical compound with the formula CH3CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.

This enzyme belongs to the family of lyases, specifically the aldehyde-lyases, which cleave carbon-carbon bonds. The systematic name of this enzyme class is L-threonine acetaldehyde-lyase (glycine-forming). This enzyme is also called L-threonine acetaldehyde-lyase. This enzyme participates in glycine, serine and threonine metabolism. It employs one cofactor, pyridoxal phosphate.

In biochemistry, a lyase is an enzyme that catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure. The reverse reaction is also possible. For example, an enzyme that catalyzed this reaction would be a lyase:

Serine is an ɑ-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, a carboxyl group, and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC.

Metabolism is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of food to energy to run cellular processes; the conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of nitrogenous wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments..

## Structural studies

As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes 1JG8, 1LW4, 1LW5, 1M6S, and 1SVV.

The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cryo-electron microscopy, and submitted by biologists and biochemists from around the world, are freely accessible on the Internet via the websites of its member organisations. The PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB.

## Presence in human and mouse

The enzyme is synthesized and functional in mice. [1]

Humans also have the remnants of the gene, coding this enzyme (GLY1), however it is damaged by past mutations and inactive. [1] Human gene contains two single nucleotide deletions causing frameshifts and premature stop codons. Also, the encoded protein would not be active anyway due mutations in other highly conserved regions. Human gene is no longer transcribed into RNA.

## Related Research Articles

Acetaldehyde dehydrogenases are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid. The oxidation of acetaldehyde to acetate can be summarized as follows:

Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can only synthesize 11 of the 20 standard amino acids, and in time of accelerated growth, histidine, can be considered an essential amino acid.

Aldolase B also known as fructose-bisphosphate aldolase B or liver-type aldolase is one of three isoenzymes of the class I fructose 1,6-bisphosphate aldolase enzyme, and plays a key role in both glycolysis and gluconeogenesis. The generic fructose 1,6-bisphosphate aldolase enzyme catalyzes the reversible cleavage of fructose 1,6-bisphosphate (FBP) into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP) as well as the reversible cleavage of fructose 1-phosphate (F1P) into glyceraldehyde and dihydroxyacetone phosphate. In mammals, aldolase B is preferentially expressed in the liver, while aldolase A is expressed in muscle and erythrocytes and aldolase C is expressed in the brain. Slight differences in isozyme structure result in different activities for the two substrate molecules: FBP and fructose 1-phosphate. Aldolase B exhibits no preference and thus catalyzes both reactions, while aldolases A and C prefer FBP.

Serine hydroxymethyltransferase (SHMT) is a Pyridoxal phosphate (PLP) (Vitamin B6) dependent enzyme (EC 2.1.2.1) which plays an important role in cellular one-carbon pathways by catalyzing the reversible, simultaneous conversions of L-serine to glycine and tetrahydrofolate (THF) to 5,10-methylenetetrahydrofolate (5,10-CH2-THF). This reaction provides the largest part of the one-carbon units available to the cell.

Cystathionine-β-synthase, also known as CBS, is an enzyme (EC 4.2.1.22) that in humans is encoded by the CBS gene. It catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine:

Serine dehydratase or L-serine ammonia lyase (SDH) is in the β-family of pyridoxal phosphate-dependent (PLP) enzymes. SDH is found widely in nature, but its structural and chemical properties vary greatly among species. SDH is found in yeast, bacteria, and the cytoplasm of mammalian hepatocytes. The reaction it catalyzes is the deamination of L-serine to yield pyruvate, with the release of ammonia.

In enzymology, a glycine N-methyltransferase is an enzyme that catalyzes the chemical reaction

Glycine decarboxylase also known as glycine cleavage system P protein or glycine dehydrogenase is an enzyme that in humans is encoded by the GLDC gene.

In enzymology, a L-serine ammonia-lyase (EC 4.3.1.17) is an enzyme that catalyzes the chemical reaction

Threonine ammonia-lyase, also commonly referred to as threonine deaminase or threonine dehydratase, is an enzyme responsible for catalyzing the conversion of L-threonine into alpha-ketobutyrate and ammonia. Alpha-ketobutyrate can be converted into L-isoleucine, so threonine ammonia-lyase functions as a key enzyme in BCAA synthesis. It employs a pyridoxal-5'-phosphate cofactor, similar to many enzymes involved in amino acid metabolism. It is found in bacteria, yeast, and plants, though most research to date has focused on forms of the enzyme in bacteria. This enzyme was one of the first in which negative feedback inhibition by the end product of a metabolic pathway was directly observed and studied. The enzyme serves as an excellent example of the regulatory strategies used in amino acid homeostasis.

In enzymology, a 4-hydroxy-2-oxovalerate aldolase is an enzyme that catalyzes the chemical reaction

In enzymology, a deoxyribose-phosphate aldolase is an enzyme that catalyzes the chemical reaction

In enzymology, a phosphatidylserine decarboxylase (EC 4.1.1.65) is an enzyme that catalyzes the chemical reaction

Glycine—tRNA ligase also known as glycyl-tRNA synthetase is an enzyme that in humans is encoded by the GARS gene.

In enzymology, an ectoine synthase (EC 4.2.1.108) is an enzyme that catalyzes the chemical reaction

In enzymology, a threonine synthase (EC 4.2.3.1) is an enzyme that catalyzes the chemical reaction

Glycine cleavage system H protein, mitochondrial is a protein that in humans is encoded by the GCSH gene. Degradation of glycine is brought about by the glycine cleavage system (GCS), which is composed of 4 protein components: P protein, H protein, T protein, and L protein. The H protein shuttles the methylamine group of glycine from the P protein to the T protein. The protein encoded by GCSH gene is the H protein, which transfers the methylamine group of glycine from the P protein to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH). Two transcript variants, one protein-coding and the other probably not protein-coding,have been found for this gene. Also, several transcribed and non-transcribed pseudogenes of this gene exist throughout the genome.

L-allo-threonine aldolase is an enzyme catalyzing the conversion between L-allothreonine on one side and glycine plus acetaldehyde on another side. Artificial disabling (knockout) of this enzyme in wild bacteria has no significant effect. However such disabling suppresses the growth of mutants that already lack other enzyme, serine hydroxymethyltransferase. Hence L-allo-threonine aldolase provides the alternative pathway for cellular glycine when serine hydroxymethyltransferase is inert. E.coli L-allo-threonine aldolase is a highly termostable enzyme, this can be used for purification.

D-threonine aldolase is an enzyme with systematic name D-threonine acetaldehyde-lyase (glycine-forming). This enzyme catalyses the following chemical reaction

Low-specificity L-threonine aldolase is an enzyme with systematic name L-threonine/L-allo-threonine acetaldehyde-lyase (glycine-forming). This enzyme catalyses the following chemical reaction

## References

1. Alasdair J Edgar (2005) Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene. BMC Genomics March 2005, 6:32. pdf
• Bell SC; Turner JM (1973). "Bacterial threonine aldolase and serine hydroxymethyltransferase enzyme". Biochem. Soc. Trans. 1: 678–681.
• KARASEK MA, GREENBERG DM (1957). "Studies on the properties of threonine aldolases". J. Biol. Chem. 227 (1): 191–205. PMID   13449064.
• Kumagai H, Nagate T, Yoshida H, Yamada H (1972). "Threonine aldolase from Candida humicola. II. Purification, crystallization and properties". Biochim. Biophys. Acta. 258 (3): 779–90. doi:10.1016/0005-2744(72)90179-9. PMID   5017702.