10-Formyltetrahydrofolate

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10-Formyltetrahydrofolate
10-formyl-tetrahydrofolic acid.svg
10-Formyltetrahydrofolate-3D-spacefill.png
Names
Preferred IUPAC name
(2S)-2-[4-(N-{[(6Ξ)-2-Amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}formamido)benzamido]pentanedioic acid
Other names
  • 10-CHO-THF
  • 10-FormylH4folate
  • N10-Formyltetrahydrofolate
Identifiers
3D model (JSmol)
ChemSpider
KEGG
MeSH 10-formyl-tetrahydrofolate
PubChem CID
  • InChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)23-11(7-22-16)8-27(9-28)12-3-1-10(2-4-12)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,11,13,23H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,22,25,26,32)/t11?,13-/m0/s1 Yes check.svgY
    Key: AUFGTPPARQZWDO-YUZLPWPTSA-N Yes check.svgY
  • c1cc(ccc1C(=O)N[C@@H](CCC(=O)O)C(=O)O)N(CC2CNc3c(c(=O)nc([nH]3)N)N2)C=O
Properties
C20H23N7O7
Molar mass 473.44 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

10-Formyltetrahydrofolate (10-CHO-THF) is a form of tetrahydrofolate that acts as a donor of formyl groups in anabolism. In these reactions 10-CHO-THF is used as a substrate in formyltransferase reactions.

Contents


Functions

Two equivalents of 10-CHO-THF are required in purine biosynthesis through the pentose phosphate pathway, where 10-CHO-THF is a substrate for phosphoribosylaminoimidazolecarboxamide formyltransferase.

10-CHO-THF is required for the formylation of methionyl-tRNA formyltransferase to give fMet-tRNA. [1]

Formation from methenyltetrahydrofolate

10-CHO-THF is produced from methylenetetrahydrofolate (CH2H4F) via a two step process. The first step generates 5,10-methenyltetrahydrofolate: [2]

CH2H4F + NAD+ CH2H2F + NADH + H+

In the second step 5,10-methenyltetrahydrofolate undergoes hydrolysis:

CH2H2F + H2O CHO-H4F +

The latter is equivalently written:

5,10-methenyltetrahydrofolate + H2O 10-formyltetrahydrofolate

10-CHO-THF is also produced by the reaction

ATP + formate + tetrahydrofolate ADP + phosphate + 10-formyltetrahydrofolate

This reaction is catalyzed by formate-tetrahydrofolate ligase.

It can be converted back into tetrahydrofolate (THF) by formyltetrahydrofolate dehydrogenase or THF and formate by formyltetrahydrofolate deformylase.

Related Research Articles

Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP or GTP supported by the energy released from another high-energy bond that leads to phosphorylation of ADP or GDP to ATP or GTP (note that the reaction catalyzed by creatine kinase is not considered as "substrate-level phosphorylation"). This process uses some of the released chemical energy, the Gibbs free energy, to transfer a phosphoryl (PO3) group to ADP or GDP. Occurs in glycolysis and in the citric acid cycle.

<span class="mw-page-title-main">Formylation</span>

Formylation refers to any chemical processes in which a compound is functionalized with a formyl group (-CH=O). In organic chemistry, the term is most commonly used with regards to aromatic compounds. In biochemistry the reaction is catalysed by enzymes such as formyltransferases.

<span class="mw-page-title-main">Serine hydroxymethyltransferase</span>

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.

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

<span class="mw-page-title-main">5,10-Methylenetetrahydrofolate</span> Chemical compound

5,10-Methylenetetrahydrofolate (N5,N10-Methylenetetrahydrofolate; 5,10-CH2-THF) is cofactor in several biochemical reactions. It exists in nature as the diastereoisomer [6R]-5,10-methylene-THF.

In enzymology, a formyltetrahydrofolate dehydrogenase (EC 1.5.1.6) is an enzyme that catalyzes the chemical reaction

In enzymology, a methylenetetrahydrofolate dehydrogenase (NAD+) (EC 1.5.1.15) is an enzyme that catalyzes a chemical reaction.

<span class="mw-page-title-main">Methionyl-tRNA formyltransferase</span>

In enzymology, a methionyl-tRNA formyltransferase (EC 2.1.2.9) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">5-formyltetrahydrofolate cyclo-ligase</span> Class of enzymes

In enzymology, a 5-formyltetrahydrofolate cyclo-ligase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Formate–tetrahydrofolate ligase</span>

In enzymology, a formate—tetrahydrofolate ligase is an enzyme that catalyzes the chemical reaction

In enzymology, a formyltetrahydrofolate deformylase (EC 3.5.1.10) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Methenyltetrahydrofolate cyclohydrolase</span>

In enzymology, a methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">MTHFD1</span>

MTHFD1 is a gene located in humans on chromosome 14 that encodes for a protein with three distinct enzymatic activities. C-1-tetrahydrofolate synthase, cytoplasmic also known as C1-THF synthase is an enzyme that in humans is encoded by the MTHFD1 gene.

<span class="mw-page-title-main">MTHFD2</span> Protein-coding gene in the species Homo sapiens

Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial is an enzyme that in humans is encoded by the MTHFD2 gene.

<span class="mw-page-title-main">5,10-Methenyltetrahydrofolate</span> Chemical compound

5,10-Methenyltetrahydrofolate (5,10-CH=THF) is a form of tetrahydrofolate that is an intermediate in metabolism. 5,10-CH=THF is a coenzyme that accepts and donates methenyl (CH=) groups.

<span class="mw-page-title-main">Phosphoribosylglycinamide formyltransferase</span>

Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2, 2-amino-N-ribosylacetamide 5'-phosphate transformylase, GAR formyltransferase, GAR transformylase, glycinamide ribonucleotide transformylase, GAR TFase, 5,10-methenyltetrahydrofolate:2-amino-N-ribosylacetamide ribonucleotide transformylase) is an enzyme with systematic name 10-formyltetrahydrofolate:5'-phosphoribosylglycinamide N-formyltransferase. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">MTHFD1L</span> Protein-coding gene in the species Homo sapiens

Monofunctional C1-tetrahydrofolate synthase, mitochondrial also known as formyltetrahydrofolate synthetase, is an enzyme that in humans is encoded by the MTHFD1L gene.

<span class="mw-page-title-main">Cyclodeaminase domain</span>

In molecular biology, enzymes containing the cyclodeaminase domain function in channeling one-carbon units to the folate pool. In most cases, this domain acts as a formimidoyltetrahydrofolate cyclodeaminase, which catalyses the cyclisation of formimidoyltetrahydrofolate to methenyltetrahydrofolate as shown in reaction (1). In the methylotrophic bacterium Methylobacterium extorquens, however, it acts as a methenyltetrahydrofolate cyclohydrolase, which catalyses the interconversion of formyltetrahydrofolate and methylenetetrahydrofolate, as shown in reaction (2).

UDP-4-amino-4-deoxy-L-arabinose formyltransferase is an enzyme with systematic name 10-formyltetrahydrofolate:UDP-4-amino-4-deoxy-beta-L-arabinose N-formyltransferase. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">MTHFD2L</span> Protein-coding gene in the species Homo sapiens

NAD-dependent methylenetetrahydrofolate dehydrogenase 2-like protein (MTHFD2L), also known as bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, is an enzyme that in humans is encoded by the MTHFD2L gene on chromosome 4. This enzyme localizes to the inner mitochondrial membrane, where it performs the NADP+-dependent dehydrogenase/cyclohydrolase activity as part of the mitochondrial pathway to convert folate to formate. It is associated with fluctuations in cytokine secretion in response to viral infections and vaccines.

References

  1. Voet, Donald (2016). Fundamentals of Biochemistry: Life at the Molecular Level (5th ed.). Wiley. pp. 1006–1007. ISBN   978-1-118-91840-1.
  2. Peter D. Pawelek; Robert E. MacKenzie (1998). "Methenyltetrahydrofolate Cyclohydrolase Is Rate Limiting for the Enzymatic Conversion of 10-Formyltetrahydrofolate to 5,10-Methylenetetrahydrofolate in Bifunctional Dehydrogenase-Cyclohydrolase Enzymes". Biochemistry. 37 (4): 1109–1115. doi:10.1021/bi971906t. PMID   9454603.