Pyrophosphate groups

Isopentenyl pyrophosphate and dimethylallyl pyrophosphate are structurally sim liar—both contain a double bond and a pyrophosphate ester unit—but the chemical reactivity expressed by each is different The principal site of reaction m dimethylallyl pyrophosphate is the carbon that bears the pyrophosphate group Pyrophosphate is a reasonably good leaving group m nucleophilic substitution reactions especially when as in dimethylallyl pyrophosphate it is located at an allylic carbon Isopentenyl pyrophosphate on the other hand does not have its leaving group attached to an allylic carbon and is far less reactive than dimethylallyl pyrophosphate toward nucleophilic reagents The principal site of reaction m isopentenyl pyrophosphate is the carbon-carbon double bond which like the double bonds of simple alkenes is reactive toward electrophiles... 

In E. coli GTP cyclohydrolase catalyzes the conversion of GTP (33) into 7,8-dihydroneoptetin triphosphate (34) via a three-step sequence. Hydrolysis of the triphosphate group of (34) is achieved by a nonspecific pyrophosphatase to afford dihydroneopterin (35) (65). The free alcohol (36) is obtained by the removal of residual phosphate by an unknown phosphomonoesterase. The dihydroneoptetin undergoes a retro-aldol reaction with the elimination of a hydroxy acetaldehyde moiety. Addition of a pyrophosphate group affords hydroxymethyl-7,8-dihydroptetin pyrophosphate (37). Dihydropteroate synthase catalyzes the condensation of hydroxymethyl-7,8-dihydropteroate pyrophosphate with PABA to furnish 7,8-dihydropteroate (38). Finally, L-glutamic acid is condensed with 7,8-dihydropteroate in the presence of dihydrofolate synthetase. 

A guanosine tetraphosphate with pyrophosphate groups in the 3 - and 5 -positions was synthesized by double phosphorylation of the corresponding guanosine 3, 5 -dipho-sphate.1501... 

Hager and Szostak used an RNA library in which each member was capped by an adenosine-5 -5 -pyrophosphate group at the 5 -end to isolate ribozymes that catalyze the ligation of an oligoribonucleotide to this activated group. This reaction results in the formation of a 3 -5 -ligation and the release of AMP [82]. 

The thiamine molecule is the stuff that is in your multivitamin pills. The active form in human physiology is thiamine pyrophosphate, in which a pyrophosphate group is added from ATP. 

In these derivatives, nucleophilic attack at the anomeric carbon atom should be greatly facilitated if the negative charges on oxygen atoms of the pyrophosphate group are removed. In consequence, intermediates such as 121, where R1 = nucleoside, and R2 = hydrogen atoms or electrophilic enzyme groups, are probable intermediates in these reactions. 

Attack at the /3 phosphate of ATP displaces AMP and transfers a pyrophosphoiyl (not pyrophosphate) group to the attacking nucleophile (Pig. 13-10b). For example, the formation of 5 -phosphoribosyl-1-pyrophosphate (p. XXX), a key intermediate in nucleotide synthesis, results from attack of an —OH of the ribose on the /3 phosphate. 

Stage (J) Condensation of Six Activated Isoprene Units to Form Squalene Isopentenyl pyrophosphate and dimethylallyl pyrophosphate now undergo a head-to-tail condensation, in which one pyrophosphate group is displaced and a 10-carbon chain, geranyl pyrophosphate, is formed (Fig. 21-36). (The head is the end to which pyrophosphate is joined.) Geranyl pyrophosphate undergoes another head-to-tail condensation with isopentenyl pyro-... 

Thiamine pyrophosphate (TPP) is the biologically active form of fre vitamin, formed by the transfer of a pyrophosphate group from ATP to thiamine (Figure 28.11). Thiamine pyrophosphate serves as a coen zyme in the formation or degradation of a-ketols by transketolase (Figure 28.12A), and in the oxidative decarboxylation of a-keto adds i (Figure 28.12B). 

Thiamine pyrophosphate (TPP) (37), a derivative of vitamin Bi (38), contains two substituted heterocycles, the pyrimidine and thiazolium rings, connected by a methylene bridge. The reactive portion of this coenzyme is the thiazolium ring, the pyrimidine portion (as well as the pyrophosphate group) being important in binding interactions with proteins... 

Chain elongation during polymerization of prenyl units can be terminated in one of a number of ways. The pyrophosphate group may be hydrolyzed to a monophosphate or to a free alcohol. Alternatively, two polyprenyl compounds may join "head to head" to form a symmetric dimer. The C30 terpene squalene, the precursor to cholesterol, arises in this way from two molecules of famesyl diphosphate as does phy-toene, precursor of the Qo carotenoids, from E,E,E geranylgeranyl diphosphate. The phytanyl groups of archaebacterial lipids (p. 385) arise rather directly from geranylgeranyl diphosphate by transfer of the poly-... 

The trinucleotide ZTP also accumulates, not only in bacteria but also in many eukaryotic cells. Bochner and Ames suggested it may be an alarmone signaling a deficit of folate coenzymes in the cell and causing a shutdown of protein synthesis. ZTP is synthesized by an unusual reaction, transfer of a pyrophosphate group from PRPP (phosphoribosyl pyrophosphate). 

Carboxymethylation. It was found by Vallee and Li that one cysteine residue per subunit may be selectively carboxymethylated with iodoacetate.1405 Since this reaction causes deactivation of the enzyme, this cysteine residue, later identified as Cys-46,1406 was suggested to be at the active site. The deactivated carboxymethylated enzyme still binds NAD+. The carboxymethylation of this residue is preceded by a reversible binding of iodoacetate to the enzyme.1407 This observation has helped to identify an anion-binding site in the coenzymebinding domain, where the pyrophosphate group of the coenzyme binds. 

Third, the products of the hydrolysis of ATP provide opportunities for coupling to a wide variety of chemical reactions. We saw how the phosphate group is incorporated into glucose-6-phosphate, and later chapters provide many illustrations of similar enzymatic processes. We also will see reactions in which the pyrophosphate group or the ade-nylyl group (AMP) is incorporated into the products. Such a broad array of reactions could not be driven by a molecule that decomposed to release an inert material such as N2. 

Synthesis of cyclic AMP. A catalytic site on adenylate cyclase ( B) removes a proton from the C-3 oxygen, which then attacks the a-phosphate and displaces the pyrophosphate group. This reaction occurs on the inner plasma membrane (see fig. 12.29). 

---