Serine hydroxymethyltransferase
Encyclopedia
Serine hydroxymethyltransferase (SHMT) is an enzyme which plays an important role in cellular one-carbon pathways by catalyzing the reversible, simultaneous conversions of L-serine
to glycine
(retro-aldol cleavage) and tetrahydrofolate to 5,10-methylenetetrahydrofolate
(hydrolysis). This reaction provides the largest part of the one-carbon units available to the cell.
and Bacillus stearothermophilus
have versions of this enzyme and there appear to be two isoforms of SHMT in mammals, one in the cytoplasm
(cSHMT) and another in the mitochondria (mSHMT). Plants may have an additional SHMT isoform within chloroplast
s.
In mammals, the enzyme is a tetramer
of four identical subunits of approximately 50,000 Daltons each. The intact holoenzyme
has a molecular weight of approximately 200,000 Daltons and incorporates four molecules of pyridoxal phosphate (Vitamin B6)
as a coenzyme
.
(SMS) is a rare disorder that manifests as a complex set of traits including facial abnormalities, unusual behaviors, and developmental delay. It results from an interstital deletion within chromosome 17p11.2, including the cSHMT gene and a small study showed SHMT activity in SMS patients was ~50% of normal. Reduced SHMT would result in less glycine which could affect the nervous system by acting as an agonist to the NMDA receptor and this could be a mechanism behind SMS.
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
to glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
(retro-aldol cleavage) and tetrahydrofolate to 5,10-methylenetetrahydrofolate
5,10-Methylenetetrahydrofolate
5,10-Methylenetetrahydrofolate is the substrate used by the enzyme methylenetetrahydrofolate reductase to generate 5-methyltetrahydrofolate ....
(hydrolysis). This reaction provides the largest part of the one-carbon units available to the cell.
Isoforms
Bacteria such as Escherichia coliEscherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
and Bacillus stearothermophilus
Bacillus stearothermophilus
Bacillus stearothermophilus is a rod-shaped, Gram-positive bacterium and a member of the division Firmicutes. The bacteria is a thermophile and is widely distributed in soil, hot springs, ocean sediment, and is a cause of spoilage in food products. It will grow within a temperature range of 30-75...
have versions of this enzyme and there appear to be two isoforms of SHMT in mammals, one in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
(cSHMT) and another in the mitochondria (mSHMT). Plants may have an additional SHMT isoform within chloroplast
Chloroplast
Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...
s.
In mammals, the enzyme is a tetramer
Tetramer
A tetramer is a protein with four subunits . There are homotetramers such as glutathione S-transferase or single-strand binding protein, dimers of hetero-dimers such as hemoglobin , and heterotetramers, where each subunit is different.-Subunit interactions in tetramers:The interactions between...
of four identical subunits of approximately 50,000 Daltons each. The intact holoenzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
has a molecular weight of approximately 200,000 Daltons and incorporates four molecules of pyridoxal phosphate (Vitamin B6)
Vitamin B6
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
as a coenzyme
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
.
Other reactions
As well as its primary role in folate metabolism, SHMT also catalyzes other reactions that may be biologically significant, including the conversion of 5,10-methenyltetrahydrofolate to 10-formyltetrahydrofolate. When coupled with C1-tetrahydrofolate synthase and tetrahydropteroate, cSHMT also catalyzes the conversion of formate to serine.Role in Smith-Magenis syndrome
Smith-Magenis syndromeSmith-Magenis syndrome
Smith–Magenis Syndrome is a developmental disorder that affects many parts of the body. The major features of this condition include mild to moderate mental retardation, distinctive facial features, sleep disturbances, and behavioral problems...
(SMS) is a rare disorder that manifests as a complex set of traits including facial abnormalities, unusual behaviors, and developmental delay. It results from an interstital deletion within chromosome 17p11.2, including the cSHMT gene and a small study showed SHMT activity in SMS patients was ~50% of normal. Reduced SHMT would result in less glycine which could affect the nervous system by acting as an agonist to the NMDA receptor and this could be a mechanism behind SMS.