Isopentenyl diphosphate pyrophosphate

Isopentenyl diphosphate (pyrophosphate) (5.5) provides the isoprene unit of the terpenoids and steroids. There are two major routes by which it is formed (Scheme 5.1). The first involves mevalonic acid (5.4) and the second, quite... 

The terpenoid precursor isopentenyl diphosphate, formerly called isopentenyl pyrophosphate and abbreviated IPP, is biosynthesized by two different pathways depending on the organism and the structure of the final product. In animals and higher plants, sesquiterpenoids and triterpenoids arise primarily from the mevalonate pathway, whereas monoterpenoids, diterpenoids, and tetraterpenoids are biosynthesized by the 1-deoxyxylulose 5-phosphate (DXP) pathway. In bacteria,... 

The conversion of isopentenyl diphosphate (IPP) to terpenoids begins with its isomerization to dimethylallyl diphosphate, abbreviated DMAPP and formerly called dimethylallyl pyrophosphate. These two C5 building blocks then combine to give the C10 unit geranyl diphosphate (GPP). The corresponding alcohol, geraniol, is itself a fragrant terpenoid that occurs in rose oil. 

Isopentenyl diphosphate is isomerized by a shift of the double bond to form dimethylallyl diphosphate, then condensed with another molecule of isopentenyl diphosphate to form the ten-carbon intermediate ger-anyl diphosphate (Figure 26-2). A further condensation with isopentenyl diphosphate forms farnesyl diphosphate. Two molecules of farnesyl diphosphate condense at the diphosphate end to form squalene. Initially, inorganic pyrophosphate is eliminated, forming presqualene diphosphate, which is then reduced by NADPH with elimination of a further inorganic pyrophosphate molecule. 

This enzyme [EC 2.5.1.27], also called 2-isopentenyl-diphosphate AMP A -isopentenyltransferase and cyto-kinin synthase, catalyzes the reaction of AMP with A -isopentenyl diphosphate to yield pyrophosphate and A -(A -isopentenyl)adenosine 5 -monophosphate. 

This enzyme [EC 4.1.1.33], also known as mevalonate pyrophosphate decarboxylase, catalyzes the reaction of ATP with (i )-5-diphosphomevalonate to produce ADP, orthophosphate, carbon dioxide, and isopentenyl diphosphate. 

This enzyme [EC 2.5.1.29], also known as geranylgera-nyl-diphosphate synthase, catalyzes the condensation of transqrans-famesyl diphosphate and isopentenyl diphosphate to yield geranylgeranyl diphosphate and pyrophosphate. 

This enzyme [EC 2.5.1.10], also known as farnesyl-di-phosphate synthase, catalyzes the reaction of geranyl diphosphate with isopentenyl diphosphate to produce trans,trans-farnesyl diphosphate and pyrophosphate (or, diphosphate). Some forms of this enzyme will also utilize dimethylallyl diphosphate as a substrate. However, the enzyme will not accept larger prenyl diphosphates as an efficient substitute for geranyl diphosphate. 

Phytoene synthase [EC 2.5.1.32] (also known as gera-nylgeranyl-diphosphate geranylgeranyltransferase and prephytoene-diphosphate synthase) catalyzes the reaction of two geranylgeranyl diphosphate to produce pyrophosphate (or, diphosphate) and prephytoene diphosphate. Isopentenyl pyrophosphate isomerase [EC 5.3.3.2] catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate. See also Geranylgeranyl Diphosphate Geranylgeranyltransferase... 

Isopentenyl diphosphate (prenyl pyrophosphate) 527, 689, 690s, 712s Isopentenyladenosine 234s Isopeptidases 525 Isopeptide linkage in proteins 80 to ubiquitin 524... 

Figure 11 Biosynthesis of isoprenoid type cofactors. 18, Heme a 39, pyridoxal 5 -phosphate 43, 1-deoxy-D-xylulose 5-phosphate 46, thiamine pyrophosphate 83, acetyl-CoA 84, (S)-3-hydroxy-3-methylglutaryl-CoA 85, mevalonate 86, isopentenyl diphosphate (IPP) 87, dimethylallyl diphosphate (DMAPP) 88, pyruvate 89, D-glyceraldehyde 3-phosphate 90, 2C-methyl-D-erythritol 4-phosphate 91, 2C-methyl-erythritol 2,4-cyclodiphosphate 92, 1-hydroxy-2-methyl-2-( )-butenyl 4-diphosphate 93, polyprenyl diphosphate 94, cholecalciferol 95, fS-carotene 96, retinol 97, ubiquinone 98, menaquinone 99, a-tocopherol.

Tetraterpenes or carotenoids are synthesized from mevalo-nate precursors. Those involved in photosynthesis are synthesized in the chloroplast, but the enzymes specific for carotenoid biosynthesis are encoded in the nucleus, synthesized in cytoplasmic ribosomes, and transported into the chloroplast (Britton, 1993). Chloroplasts at different stages in development seem to differ in their ability to synthesize carotenoids autonomously from CO2 or by importation of isopentenyl pyrophosphate (isopentenyl diphosphate) (Britton, 1993). 

The isomerization of isopentenyl diphosphate to dimethylallyl diphosphate is catalyzed by the enzyme isopentenyl pyrophosphate isomerase. In this process, the 2R hydrogen is lost and another hydrogen is picked up on the opposite face. Thus, the original methyl group is now cis or (Z)- to the methylene bearing the diphosphate group, that is. 

As mentioned above, terpenoids can be seen as built up by isoprene units. In vivo, these units are the interconvertible isomers isopentenyl diphosphate IPP (isopentenyl pyrophosphate) and dimethylallyl diphosphate (DMAPP) (dimethylallyl pyrophosphate). 

Diterpenes are formed by head (isopropylidene end) to tail (alcohol end) of four isoprene (CsHg) building blocks. The isoprene unit itself originates by the decomposition of natural cyclic hydrocarbons giving rise to the biochemically active isoprene units, identified as the pyrophosphate esters dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) (Scheme 102.1). 

Terpenes are synthesised in organisms by complex mechanisms from isoprene units, isopentenyl phosphate and dimethy-lallyl diphosphate (pyrophosphate). The first product is geranyl diphosphate, which is the universal precursor of monoterpenoids. The reaction of geranyl diphosphate with another molecule of isopentenyl diphosphate yields famesyl diphosphate, which is the precursor of sesquiterpenoids. Further reaction with isopentenyl diphosphate gives geranylgeranyl diphosphate, the precursor of diterpenoids (see Figure 3.10). 

Figure 16.2). Dimethylallyl pyrophosphate (DMAPP), the common consohdated metabolite of both pathways, is converted to isoprene by isoprene synthase (IspS). DMAPP and its isomer isopentenyl diphosphate (IPP) are also the building units of terpenes and higher isoprenoids (see Section 16.5) in all living organisms [12]. 

Biosynthetically, all terpenoids are traced back to a common synthon of biochemically active isoprene unit found in the forms of pyrophosphate esters either as dimeth-ylallyl diphosphate (DMAPP) or isopentenyl diphosphate (IPP) (Fig. 5.1). In turn, DMAPP and IPP are derived by two distinct biosynthetic pathways, the mevalonate pathway (MVA pathway) and the mevalonate-independent pathway or pathway of deoxyxylulose phosphate (DXP pathway), which are considered to be the major natural synthetic routes for the synthesis of terpenoids (Fig. 5.2). 

Isopentenyl pyrophosphate is potentially a bifunctional molecule. Its terminal vinyl group gives a nucleophilic character whereas when it isomerizes to 3,3-dimethylallyl diphosphate, the latter is electrophilic. Thus, longer-chain polyprenyls are formed by a favourable condensation of isopentenyl pyrophosphate first with dimethylallyl pyrophosphate and later with other allylic diphosphates. The initial interconversion of isopentenyl diphosphate and dimethylallyl diphosphate is promoted by an isomerase. The successive condensations yield the Cio compound geranyl diphosphate and then the C15 farnesyl diphosphate. The two molecules of famesyl diphosphate condense to form presqualene pyrophosphate which is reduced by NADPH to give the C30 open chain terpenoid squalene. The condensation reactions with IPP are a rather novel method of C-C bond formation since in the formation of other types of natural products (peptides, sugars, fatty acids, etc.) the reactions involve Claisen- or aldol-type condensations. 

Nicotinamide adenine dinucleotide (NAD) Fructose 1,6-diphosphate Glucose-6-phosphate Isopentenyl pyrophosphate Ribose-6-phosphate-l-pyrophosphate... 

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