section 27.2

Formation of

5

-PhosphoribosyI-

1

-Pyrophosphate

619

Folic acid (F)

FH,

- NADPH + H

•NADP+

•NADPH + H

■NADP+

FIGURE 27-5

One-carbon transfer reactions involving folate-derived carriers. Dashed arrows indicate multiple-step reaction pathways;

solid arrows represent direct, single-step reactions.

reactions are shown in Figure 27-5. Serine, a nonessential

amino acid, is the major source of one-carbon frag-

ments. Some key processes that utilize folate-mediated

one-carbon transfer reactions are as follows:

1. Synthesis of purine nucleotides (N10-formyl FH

4

);

2. Méthylation of deoxyuridylate to thymidylate

(N

5

,N10-methylene FH4) (an essential step in the

biosynthesis of DNA; impairment of this reaction is

responsible for the main clinical manifestations of

folate deficiency);

3. Synthesis of formylmethionyl-tRNA

(N10-formyl FH4) required for initiation of protein

synthesis in prokaryotes (Chapter 25) and in

mitochondria; and

4. Conversion of homocysteine to methionine

(N5-methyl FH4) (Chapter 17).

Inherited disorders of folate transport and metabolism

include defects in folate carrier (hereditary folate mal-

absorption, previously discussed), deficiency of N

5

,N10-

methylene FH

4

reductase (Chapter 17), or functional defi-

ciency of N5-methyl FH

4

methyltransferase due to defects

of vitamin B

12

metabolism (Chapter 38) or formimino-

transferase (previously discussed).

Several observational studies have shown that dietary

supplementation of folate in women of childbearing age

who might become pregnant can reduce the risk of fetal

neural tube defects (e.g., spina bifida).

27.2 Formation of

5-Phosphoribosyl-1-Pyrophosphate

5-Phosphoribosyl-l-pyrophosphate (PRPP) is a key in-

termediate in nucleotide biosynthesis. It is required

for

de novo

synthesis of purine and pyrimidine nu-

cleotides and the salvage pathways, in which purines

are converted to their respective nucleotides via trans-

fer of ribose 1-phosphate group from PRPP to the base;

that is,

Purine + P-ribose-P-P

purine-ribose-P + PP;

(PRPP)

PRPP is synthesized from ribose 5-phosphate by the

following reaction: