A-----pyrophosphate

Ligases (syniheiases). Enzymes catalysing the joining together of two molecules coupled with the hydrolysis of a pyrophosphate bond in ADP or a similar triphosphate. They include some carboxylases and many enzymes known as synthetases. 

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 keeping with its biogenetic origin m three molecules of acetic acid mevalonic acid has six carbon atoms The conversion of mevalonate to isopentenyl pyrophosphate involves loss of the extra carbon as carbon dioxide First the alcohol hydroxyl groups of mevalonate are converted to phosphate ester functions—they are enzymatically phosphorylated with introduction of a simple phosphate at the tertiary site and a pyrophosphate at the primary site Decarboxylation m concert with loss of the terti ary phosphate introduces a carbon-carbon double bond and gives isopentenyl pyrophos phate the fundamental building block for formation of isoprenoid natural products... 

Section 26 9 Carbon-carbon bond formation between isoprene units can be understood on the basis of nucleophilic attack of the tt electrons of a double bond on a carbocation or an allyhc carbon that bears a pyrophosphate leaving group... 

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. 

Ligases (synthetases) - catalyzing the condensation of 2 molecules coupled with the cleavage of a pyrophosphate bond of ATP or similar triphosphate. 

The condensation reactions are preferentially carried out in pyridine. As reactive species for phosphorylation of the nucleoside R OH (synthesis of a phosphortriester), the phosphoric acid azolide has been assumed. The mixed phosphoric sulfonic anhydride and a pyrophosphate tetraester have been suggested as intermediates leading to the phosphoric acid azolide. 

Such enzymes catalyse the condensation of specific compounds, accompanied by the breakdown of a pyrophosphate bond in adenosine triphosphate (10.64). Adenosine is the condensation product of a pentose (D-ribofuranose) and a purine (adenine). Scheme 10.15 shows the action of glutamine synthetase on a mixture of L-glutamic acid (10.65) and... 

Figure 5.4. Schematic illustration of the cyclodextrin catalysed fission of a pyrophosphate derivative (Hennrich Cramer, 1965). 

Additional steps occur in the case of eubacteria, namely syntheses of various dinucleotide forms of the cofactor, in which the pyranopterin is linked to a second nucleotide via a pyrophosphate linkage [34]. 

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. 

PRPP 5-Phosphoribosyl-a-pyrophosphate Tris Tris(hydroxymethyl)aminomethane... 

Reactions in the second stage occur when precursor units move along the cytoplasmic membrane. In the first reaction, the M-acetylmuramylpentapeptide region binds (through a pyrophosphate bridge) to a carrier phospholipid that is bound to the cytoplasmic membrane. M-acetylglucosamine is then bound, forming a disaccharide-pentapeptide-P-P-phospholipid. 

Antibodies against the virus but also amantadine and derivatives, interfere with host cell penetration. There are nucleoside analogues such as aciclovir and ganciclovir, which interfere with DNA synthesis, especially of herpes viruses. Others like zidovudine and didanosine, inhibit reverse transcriptase of retroviruses. Recently a number of non-nucleoside reverse transcriptase inhibitors was developed for the treatment of HIV infections. Foscarnet, a pyrophosphate analogue, inhibits both reverse transcriptase and DNA synthesis. Protease inhibitors, also developed for the treatment of HIV infections, are active during the fifth step of virus replication. They prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new vi-rons. 

L D. The conversion of penciclovir to its active form requires initial monophosphorylation by viral thymidine kinases, then conversion to its active triphosphate form by cellular enzymes. Thus, the concentration of penciclovir triphosphate is particularly high in cells infected with its target viruses (e.g., HSV, VZV, HBV). Foscarnet is a pyrophosphate analogue that does not require activation. Oseltamivir is a neuraminidase inhibitor that is con-... 

Rubber is synthesized and sequestered on cytsolic vesicles known as rubber particles. Rubber transferase is localized to the surface of the rubber particles, and biosynthesis is initiated through the binding of an allylic pyrophosphate (APP, a pyrophosphate, produced by soluble trans- rtnyl transferases) primer. Progressive additions of IPP molecules ultimately result in the formation of high molecular weight cjT-l,4-polyisoprene. The rubber transferase also requires a divalent cation, such as Mg + or Mn +, as cofactor. 

Bone contains at least two different acid phosphatases and the more abundant enzyme may function as a pyrophosphate. The physiological substrate for the latter enzyme may be pyrophosphate or another oligophosphate ester. The first enzyme may utilize only monophosphate esters. 

If we consider the urea cycle in isolation, we see that the synthesis of one molecule of urea requires four high-energy phosphate groups (Fig. 18-10). Two ATP molecules are required to make carbamoyl phosphate, and one ATP to make argininosuccinate—the latter ATP undergoing a pyrophosphate cleavage to AMP and PPj, which is hydrolyzed to two Pj. The overall equation of the urea cycle is... 

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). 

Lack of a pyrophosphate ion pump in cartilage cells may cause a deficit in pyrophosphate in the surroundings of the forming bone. In mice with a defect in this pump bony spurs, similar to those in human osteoarthritis, are formed.7113 Over half of the world s population of persons over 65 years of age are afflicted by arthritis, over 100 types being known.711b... 

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