What is THF in purine synthesis?

Tetrahydrofolates (THF)2 serve as a family of cofactors that carry and activate one-carbons for the synthesis of purines and thymidylate and for the remethylation of homocysteine to methionine (Figs. 1 and 2) (1).

Is THF required for pyrimidine synthesis?

Because tetrahydrofolate is required for purine and pyrimidine synthesis, its deficiency can lead to inhibition of DNA, RNA, and protein synthesis, which are essential for the growth and survival of both normal cells and cancer cells.

How is purine synthesized?

Biosynthesis. Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ribose 5-phosphate. Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which is the first compound in the pathway to have a completely formed purine ring system.

How is GMP synthesized IMP?

The formation of GMP from IMP requires oxidation at C-2 of the purine ring, followed by a glutamine-dependent amidotransferase reaction that replaces the oxygen on C-2 with an amino group to yield 2-amino,6-oxy purine nucleoside monophosphate, or as this compound is commonly known, guanosine monophosphate.

What is the role of Tetrahydrofolate?

Tetrahydrofolate is the main active metabolite of dietary folate. It is vital as a coenzyme in reactions involving transfers of single carbon groups. Tetrahydrofolate has a role in nucleic and amino acid synthesis.

Why is THF important?

Tetrahydrofolic acid (THF) acts as the carrier for one-carbon groups, necessary for many biosynthetic pathways such as amino acid and nucleic acid metabolism. Notably, THF is an essential precursor in the thymidine synthesis pathway.

How is tetrahydrofolate important to purine synthesis?

In turn, tetrahydrofolate serves as the carrier of various one-carbon groups that are added to, or abstracted from, metabolites such as histidine, serine, methionine, purines, and thymidylate.

What is the role of THF?

THF is widely used as a solvent for special resins such as photosensitive resins, because even at room temperature it can dissolve various resins, and it is miscible with water and most organic solvents. In, addition, it is used as a solvent for Grignard and Wittig reactions.

Where are purines synthesized?

cytosol
Commitment Step. De novo purine nucleotide synthesis occurs actively in the cytosol of the liver where all of the necessary enzymes are present as a macro-molecular aggregate.

How many steps are in purine synthesis?

ten-step
Purine synthesis is a ten-step process that requires ribose-5-phosphate from the PPP, glycine and formate from the serine/glycine synthesis pathway, glutamine, and TCA cycle-derived aspartate.

How purines are synthesized in Denovo synthesis?

In the de novo purine synthesis pathway, the purine ring is sequentially constructed from small molecule donors on a ribose 5-phosphate backbone provided by 5-phosphoribosyl-1-pyrophosphate (PRPP) to form the first purine product, inosine monophosphate (IMP) (Figure 38.2).

What is the structural component of tetrahydrofolate?

Chemically folic acid consists of three structural components- para-aminobenzoic acid (PABA), a bicyclic pteridine ring, and glutamic acid.

What is purine synthesis?

Purine Synthesis: Synthesis of Purine RiboNucleotides Purines that result from the normal turnover of cellular nucleic acids or that is obtained from the diet and not degraded. It can be reconverted into Nucleoside triphosphate and used by the body. This is referred to as the “Salvage pathway” for Purines.

Does tetrahydrofolate interfere with purine synthesis?

Although not shown, tetrahydrofolate is involved in two reactions of de novo purine synthesis. Folic acid analogs, such as methotrexate, inhibit the formation of tetrahydrofolate and thus interfere with purine synthesis.

How is purine nucleotide synthesized from ribose 5-phosphate?

3.  Ribose 5-phosphate, of carbohydrate metabolism is the starting material for purine nucleotide synthesis.  It reacts with ATP to form phosphoribosyl pyrophosphate (PRPP).  Glutamine transfers its amide nitrogen to PRPP to replace pyrophosphate & produce 5- phosphoribosylamine.

What is the role of PRPP in purine biosynthesis?

(a) 5′-Phosphoribosyl 1′-pyrophosphate (PRPP), which provides the ribose moiety, reacts with glutamine to form phosphoribosylamine. This first step in purine biosynthesis produces N9 of the purine ring and is inhibited by AMP and GMP.