Geranyl geranylation

Seabra, M. C., Brown, M. S. and Goldstein, I. L. Retinal degeneration in choroideremia deficiency of rat geranyl-geranyl transferase. Science 259 377-381,1993. 

Proteins with an isoprenoid modification possess either a C15-famesyl residue or a C20-geranyl-geranyl residue. Both residues are bound via a thioester linkage to a cysteine residue. As with myristoylation, these are constitutive, stable modification performed by farnesyl or geranyl transferases. 

The prenyl transferases are a class of enzymes that is involved in post-translational modification of membrane-associated proteins. These enzymes catalyze the transfer of a farnesyl (FTase, EC 2.5.1.58, for structural information see References 55-65) or geranyl-geranyl group (GGTase I, EC 2.5.1.59 GGTase n, EC 2.5.1.60, for structural information... 

These results suggest that samples of this sponge differ in their enzymatic capabilities concerning the cyclization of geranyl-geranyl-pyrophosphate. 

Isoprenoid structures for carotenoids, phytol, and other terpenes start biosynthetically from acetyl coenzyme A (89) with successive additions giving mevalonate, isopentyl pyrophosphate, geranyl pyrophosphate, farnesyl pyrophosphate (from which squalene and steroids arise), with further build-up to geranyl geranyl pyrophosphate, ultimately to a- and /3-carotenes, lutein, and violaxanthin and related compounds. Aromatic hydrocarbon nuclei are biosynthesized in many instances by the shikimic acid pathway (90). More complex polycyclic aromatic compounds are synthesized by other pathways in which naphthalene dimerization is an important step (91). 

IV. Biosynthesis of cyclic dlterpenes from trans-geranyl-geranyl pyrophosphate." J. Biol. Chem., 19 % 2kh, 3200-3209. 

Moore, T.C., Coolbaugh, R.C. "Conversion of geranyl-geranyl pyrophosphate to ent-kaurene in enzyme extracts of sonicated chloroplasts." Phytochemistry, 1976, 15, 12kl 12k7. 

Membrane attachment of Ras requires covalent addition of lipids. Virtually all members of the Ras superfamily are prenylated.io Farnesylation is essential. Defects in lipid modification make Ras non-functional. A 15-carbon farnesyl or 20-carbon geranyl-geranyl chain is attached to a cysteine in the COOH-terminus of Ras. The linkage is by a thioether bond and irreversible, and therefore not a point of regulatory control, n ... 

Overhand, M., et al. (1998). Inhibitors of protein farnesyltransferase and protein geranyl-geranyl transferase I Synthesis of homologous diphosphonate analogues of isoprenylated pyrophosphate. Bioorg Chem 26 269-282. 

Fig. 2 (A) Structures of bacteriochlorophylls a and b. For BChl a, the substituents Rj and R2 are -H and either phytyl or geranyl-geranyl, respectively. For BChl b, R, is =C-CH, (with omission of the adjacent hydrogen on ring II) and R2 is either phytyl (Rhodopseudomoms viridis) or 2,10-phytadienyl (Ectothiorhodospira halochloris). (B) Structures of bacteriochlorophylls c, d and e. R, is mostly far-nesyl for green sulfur bacteria, mainly stearyl for Chloroflexus auraniiacus. R2-R5 are various substituents each BChl exists as a series of homologs.

Tocopherols eind tocotrienols are importeint constituents of chloroplast membranes in green plants, tmd are tilso found in large amounts in seeds. The aromatic ring arises from homogentisic acid, which is both a precursor of aromatic amino acids and also tm intermediate in the catabolism of tyrosine. The side chain is formed by the addition of geranyl-geranyl pyrophosphate to yield initially 5-tocotrienol. Successive methylation of the ring results in the formation of and a-tocotrienols the tocopherols are formed by reduc-... 

Prenylation also influences the balance between myocyte viability and apoptosis. Statin-induced apoptosis has been demonstrated in vitro, using myotubes [84], myoblasts [85], and differentiated primary human skeletal muscle cells [86], This effect can be reproduced by geranyl-geranyl-transferase inhibitors, and rescued by replacement of mevalonic acid [84], Compelling evidence suggests that statins cause apoptosis in skeletal muscle by disrupting the prenylation of small G proteins like Rho [85],... 

One might imagine that regioselectivity in the case of either geranyl geranyl acetate 154 (with four double bonds) or squalene 155 (with six double bonds - notice the symmetry here) would be a tricky business. 

The higher terpenes are formed not by successive addition of C5 units but by the coupling of simpler terpenes. Thus, the triterpenes (C30) are derived from two molecules of famesyl pyrophosphate, and the tetraterpenes (C40) from two molecules of geranyl-geranyl pyrophosphate. These carbon-carbon bond-forming processes involve tail-to-tail couplings and proceed by a more complicated mechanism than that just described. 

It is possible that an analogous intermediate is involved in phytoene (8) biosynthesis. However, instead of a reductive elimination of pyrophosphate, as in squalene biosynthesis, the 15(15 )-double bond must be derived by elimination. Goodwin and co-workers have shown that both protons of this double bond are labelled by [2- C,3R,5R- H]mevalonic acid. Porter and co-workers have studied the kinetics of an enzyme system from tomatoes for the conversion of geranyl geranyl pyrophosphate (6 n = 3) into phytoene. 

---