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Geranylgeranyl pyrophosphate

Geranylgeranyl pyrophosphate (GGPP), also known as geranylgeranyl diphosphate, is a C₂₀ isoprenoid intermediate in the mevalonate pathway of isoprenoid biosynthesis, characterized by a linear chain of four isoprene units in an all-trans configuration linked to a pyrophosphate moiety (chemical formula C₂₀H₃₆O₇P₂). It is synthesized by geranylgeranyl diphosphate synthase (GGDPS or GGPPS) through the head-to-tail condensation of farnesyl diphosphate (FPP, C₁₅) with isopentenyl pyrophosphate (IPP, C₅), a key step in producing longer-chain prenyl donors essential for diverse cellular processes.^[1] In biological systems, GGPP plays a central role as a lipid donor in the post-translational prenylation of proteins, particularly the geranylgeranylation of cysteine residues in small GTPases such as those in the Ras, Rho, and Rab families, which anchors these proteins to cellular membranes and facilitates their involvement in signal transduction, cytoskeletal dynamics, vesicular trafficking, and cell proliferation.^[1] Beyond protein modification, GGPP serves as a precursor for the synthesis of various terpenoids, including diterpenes (e.g., gibberellins in plants), carotenoids, and ubiquinones, contributing to pigmentation, hormone regulation, and antioxidant defense across organisms.^[1] Dysregulation of GGPP levels, often linked to altered GGDPS activity, is implicated in human diseases such as cancers (e.g., multiple myeloma and pancreatic adenocarcinoma), type 2 diabetes, Alzheimer's disease, and bone disorders, where it affects protein function and cellular homeostasis.^[1] Therapeutically, GGPP biosynthesis has emerged as a target for intervention; inhibitors of GGDPS or upstream mevalonate pathway enzymes (e.g., statins and bisphosphonates) disrupt prenylation, showing preclinical efficacy in reducing tumor growth, enhancing autophagy in cancer cells, and modulating osteoclast activity in bone diseases, with ongoing research exploring selective GGDPS inhibitors for improved specificity and reduced side effects.^[1]

Chemical characteristics

Molecular structure

Geranylgeranyl pyrophosphate (GGPP) is a C20 isoprenoid lipid with the molecular formula C_{20}H_{36}O_7P_2.^[2] It consists of a linear hydrocarbon chain composed of four isoprene units, totaling 20 carbon atoms, attached at one terminus to a pyrophosphate group via an ester linkage.^[3] The carbon skeleton features a polyene structure with four double bonds, specifically at positions 2-3, 6-7, 10-11, and 14-15, along with methyl branches at carbons 3, 7, 11, and 15, giving it the systematic IUPAC name (2E,6E,10E,14E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-yl trihydrogen diphosphate.^[2] The pyrophosphate moiety is formed by two phosphate groups linked by an oxygen bridge, with the first phosphate esterified to the primary alcohol at carbon 1 of the geranylgeranyl chain (CH_2OPO_3H_2-OPO_3H_2).^[2] Textually, the structure can be represented as a tail-to-head condensation product: the geranylgeranyl alcohol chain is (CH_3)_2C=CH-CH_2-[CH_2-C(CH_3)=CH-]_3CH_2OH, where the brackets denote repeating isoprenoid motifs, and the terminal OH is phosphorylated to yield the diphosphate. In biological contexts, GGPP predominantly adopts the all-E (trans) configuration at all four double bonds, conferring rigidity and hydrophobicity to the molecule essential for its interactions.^[3] This stereochemistry is specified as (2E,6E,10E,14E), distinguishing it from cis isomers that are less common in nature.^[2]

Physical and chemical properties

Geranylgeranyl pyrophosphate (GGPP) has a molar mass of 450.44 g/mol.^[4] It is a solid.^[5] Due to the polar pyrophosphate head group contrasted with the lipophilic C20 isoprenoid tail, GGPP exhibits amphiphilic character; it is practically insoluble in water (predicted solubility ~0.0046 g/L) but soluble in polar organic solvents such as methanol and ethanol, and insoluble in nonpolar hydrocarbons.^[5]^[6] GGPP is hydrolytically unstable, particularly under acidic or basic conditions, where it undergoes dephosphorylation to form geranylgeraniol or inorganic phosphate.^[7] This instability necessitates storage at -20°C in buffered solutions to minimize degradation.^[4] Chemically, GGPP serves as an allylic electrophile in prenyl transfer reactions, where the pyrophosphate acts as a good leaving group, facilitating the attachment of the geranylgeranyl moiety to nucleophilic substrates like proteins or other acceptors in enzymatic processes.^[8] The pyrophosphate linkage is particularly susceptible to nucleophilic attack, contributing to its role in biosynthetic pathways.^[9] Spectroscopically, GGPP displays UV absorption around 202-210 nm attributable to its double bonds in the isoprenoid chain.^[10] In NMR, the proton spectrum features characteristic signals for the trans-alkene protons (δ ~5.0-5.2 ppm) and the methylene groups adjacent to the pyrophosphate (δ ~4.6 ppm), while the carbon spectrum shows peaks for the olefinic carbons (δ ~120-140 ppm) and phosphate-bearing carbon.^[5]

Biosynthesis

In the mevalonate pathway

The mevalonate pathway serves as the canonical route for isoprenoid biosynthesis in eukaryotes, archaea, and the cytosol of plants, converting acetyl-CoA into the universal C5 building blocks isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP).^[11] This process initiates with the Claisen condensation of two acetyl-CoA molecules to acetoacetyl-CoA, followed by the addition of a third acetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA).^[11] HMG-CoA is then reduced to mevalonate in a rate-limiting step requiring two equivalents of NADPH.^[11] Mevalonate undergoes sequential phosphorylation at the C5 hydroxyl group by ATP-dependent kinases to yield 5-phosphomevalonate and then 5-diphosphomevalonate, culminating in ATP-dependent decarboxylation and dehydration to produce IPP.^[11] IPP is subsequently isomerized to DMAPP, the allylic isomer that initiates chain assembly.^[11] The pathway proceeds through iterative head-to-tail condensations of IPP units onto allylic pyrophosphate primers, releasing pyrophosphate (PPi) in each step to drive the reactions forward.^[11] First, DMAPP condenses with one IPP molecule to form the C10 intermediate geranyl pyrophosphate (GPP).^[11] GPP then extends by another IPP to yield the C15 farnesyl pyrophosphate (FPP).^[11] The final elongation incorporates a third IPP onto FPP, producing the C20 geranylgeranyl pyrophosphate (GGPP) via the reaction FPP + IPP → GGPP + PPi.^[11] This step is catalyzed by geranylgeranyl pyrophosphate synthase (GGPPS), marking the culmination of the core mevalonate pathway for GGPP production.^[11] In plants and many bacteria, an alternative non-mevalonate route known as the methylerythritol phosphate (MEP) pathway generates IPP and DMAPP from glyceraldehyde 3-phosphate and pyruvate, providing a parallel source for these precursors that can feed into downstream condensations.^[12]

Enzymes and regulation

Geranylgeranyl pyrophosphate synthase (GGPPS), also known as geranylgeranyl diphosphate synthase (GGDPS), is the primary enzyme responsible for catalyzing the formation of GGPP, functioning as a trans-prenyltransferase in the mevalonate pathway.^[1] This enzyme condenses farnesyl pyrophosphate (FPP) with isopentenyl pyrophosphate (IPP) to produce the C20 isoprenoid GGPP.^[13] The catalytic mechanism of GGPPS involves a Mg²⁺-dependent, three-step ionization-condensation-elimination reaction, where two conserved aspartate-rich motifs (DDxxD) in the active site chelate Mg²⁺ ions to facilitate substrate binding and the nucleophilic attack of IPP on FPP.^[13] Human GGPPS typically requires three Mg²⁺ ions per active site for optimal coordination of the pyrophosphate groups of IPP and FPP, with the allylic substrate (FPP) binding first followed by IPP.^[14] The enzyme's active site accommodates these substrates in a manner that promotes the release of pyrophosphate and formation of the new C-C bond, yielding all-trans-GGPP.^[13] In humans, GGPPS is encoded by a single gene (GGPS1), producing one primary isoform that forms a homohexameric structure essential for its activity.^[13] In contrast, plants exhibit multiple GGPPS isoforms encoded by gene families, often with tissue-specific and subcellular localization patterns; for example, Arabidopsis thaliana has up to 12 paralogs, including plastid-targeted isoforms like AtGGPPS11 that support carotenoid and chlorophyll synthesis in photosynthetic tissues, while others such as AtGGPPS2 are associated with gibberellin production in roots and siliques.^[15] In tomato (Solanum lycopersicum), three plastid-localized isoforms (SlGGPPS1-3) show differential expression, with SlGGPPS2 and SlGGPPS3 predominant in leaves and fruits during ripening to meet demands for terpenoid precursors.^[16] GGPPS activity is regulated through feedback inhibition by its product GGPP, which competitively binds to the allylic substrate site, thereby limiting excessive accumulation.^[13] Transcriptional regulation involves pathways like ERK/EGR1 signaling, which modulates GGPS1 expression in response to cellular needs, such as during inflammation or proliferation.^[17] Additionally, in plants, isoform-specific interactions with regulatory proteins, such as small subunit of Rubisco (SSU-II), influence substrate flux toward particular terpenoid branches.^[18] Inhibitors targeting GGPPS include nitrogen-containing bisphosphonates like zoledronate, which bind to the Mg²⁺ cluster in the active site, disrupting catalysis and reducing GGPP levels; this has been exploited in preclinical models for cancers and bone disorders due to downstream effects on protein prenylation.^[19] Lipophilic analogs of zoledronate, such as BPH-703, exhibit enhanced potency with Ki values around 270 nM by occupying a hydrophobic tunnel in the enzyme dimer.^[20] Evolutionarily, GGPPS displays homology across eukaryotes, archaea, and bacteria, stemming from a common ancestral prenyltransferase with conserved catalytic motifs like FARM and SARM, though quaternary structures vary—hexameric in mammals versus dimeric in bacteria and many plants.^[21] In plants, lineage-specific gene duplications, including whole-genome events around 48 million years ago in Arabidopsis, have driven subfunctionalization and neofunctionalization, enabling specialized roles in diverse terpenoid metabolisms.^[21] This conservation underscores GGPP's fundamental role in isoprenoid biosynthesis across domains of life.^[22]

Biological functions

Role in protein modification

Geranylgeranylation is a post-translational modification in which geranylgeranyl pyrophosphate (GGPP), a 20-carbon isoprenoid lipid, is covalently attached to the cysteine residue of target proteins via a thioether bond, facilitating their anchoring to cellular membranes.^[23] This process is essential for the proper localization and function of various signaling proteins, particularly small GTPases that regulate cellular processes such as vesicle trafficking, cytoskeletal dynamics, and signal transduction.^[24] The attachment of GGPP is catalyzed by two distinct geranylgeranyltransferases: protein geranylgeranyltransferase type I (GGTase I) and type II (GGTase II). GGTase I recognizes proteins bearing a C-terminal CAAX motif (where C is cysteine, A is typically an aliphatic amino acid, and X is a variable residue, often leucine for geranylgeranylation), transferring the geranylgeranyl group from GGPP to the cysteine thiol.^[25] In contrast, GGTase II, also known as Rab geranylgeranyltransferase, modifies Rab GTPases, which often lack a classical CAAX motif and instead receive one or two geranylgeranyl groups at a C-terminal cysteine, sometimes in conjunction with upstream cysteines.^[26] Key targets include Rho family GTPases such as RhoA, which are modified by GGTase I and crucial for actin cytoskeleton organization and cell migration, and the Rab family of GTPases, which control intracellular membrane trafficking.^[27] These modifications enable the proteins to associate with lipid bilayers, activating downstream signaling pathways.^[28] The geranylgeranylation mechanism for CAAX-bearing proteins involves sequential steps following the initial prenyl transfer. The reaction begins with the zinc-dependent nucleophilic attack by the cysteine thiol on the GGPP, displacing pyrophosphate (PPi):

\text{Protein-Cys-SH} + \text{GGPP} \rightarrow \text{Protein-Cys-S-GGPP} + \text{PP}_\text{i}

^[23] Subsequently, the AAX tripeptide is proteolytically cleaved by the endoprotease RCE1, exposing the prenylated cysteine carboxyl group, which is then methylated by the isoprenylcysteine carboxyl methyltransferase (ICMT).^[29] For Rab proteins processed by GGTase II, the pathway similarly includes prenylation followed by methylation, often with additional geranylgeranylation on a second site, but without the AAX cleavage step.^[30] Inhibition of geranylgeranylation, such as through GGTase inhibitors or depletion of GGPP, disrupts these modifications, resulting in mislocalized proteins that accumulate in the cytosol rather than associating with membranes.^[31] This mislocalization impairs the function of Rho GTPases, leading to defects in cytoskeletal regulation, and Rab GTPases, causing disruptions in vesicular transport and endocytic pathways, with broader implications for cellular homeostasis and disease states like cancer and neurodegeneration.^[27]

Involvement in terpenoid synthesis

Geranylgeranyl pyrophosphate (GGPP) serves as the primary C₂₀ precursor for the biosynthesis of diterpenes and higher terpenoids in various organisms, particularly through cyclization reactions catalyzed by terpene synthases. These enzymes initiate the folding of the linear GGPP chain into cyclic structures, often involving carbocation intermediates in class I synthases or protonation at the double bond in class II synthases, leading to diverse diterpene skeletons such as kaurene or copalyl diphosphate. In plants, this process is crucial for generating structural diversity in terpenoid natural products, with terpene synthases exhibiting substrate specificity for GGPP to produce bioactive diterpenes.^[32]^[33] A key application of GGPP in terpenoid synthesis is its role in carotenoid production, where two molecules of GGPP undergo head-to-head condensation catalyzed by phytoene synthase to form the C₄₀ intermediate prephytoene pyrophosphate, which is subsequently converted to phytoene, the first committed carotenoid. This reaction establishes the symmetrical backbone for downstream desaturation and cyclization steps yielding pigments like lycopene and β-carotene, essential for photosynthesis and photoprotection in plants. In plants, GGPP derived from the methylerythritol phosphate (MEP) pathway in plastids is preferentially channeled into carotenoid biosynthesis, highlighting the organelle's role in compartmentalizing these reactions to support chloroplast function.^[34]^[35] GGPP also functions as a precursor for plant hormones such as gibberellins, where it cyclizes via ent-kaurene synthase (a class II diterpene synthase) to form ent-kaurene, followed by oxidative modifications to yield bioactive gibberellins that regulate growth and development. Additionally, GGPP contributes to the synthesis of tocopherols (vitamin E) by providing the geranylgeranyl chain, which is hydrogenated stepwise to phytyl pyrophosphate for attachment to the chromanol ring, enhancing antioxidant activity in membranes. In certain contexts, GGPP-derived polyisoprenoid tails are incorporated into ubiquinones and plastoquinones, supporting electron transport in mitochondria and chloroplasts, respectively, though longer chains are often extended from farnesyl pyrophosphate in plants. These pathways underscore GGPP's versatility as a scaffold for essential terpenoids across cellular compartments.^[36]^[37]^[38]

Functions in specific organisms

In plants, geranylgeranyl pyrophosphate (GGPP) serves as a critical precursor for the biosynthesis of gibberellins, which are essential plant growth hormones that regulate stem elongation, seed germination, and flowering.^[39] Additionally, GGPP contributes to the production of chlorophylls and carotenoids, enabling proper chloroplast development and photosynthesis, while its depletion leads to chlorotic phenotypes and impaired photomorphogenesis. For instance, geranylgeranyl diphosphate synthases (GGPPS) play a key role in carotenoid biosynthesis in species like Osmanthus fragrans, influencing floral pigmentation and scent production.^[40] GGPP levels also modulate plant responses to abiotic stresses, such as drought and salinity, by influencing terpenoid-derived signaling molecules that enhance tolerance and growth under adverse conditions.^[41] In humans and mammals, GGPP integrates into the mevalonate pathway alongside cholesterol biosynthesis, where it supports the prenylation of proteins involved in cellular signaling and membrane dynamics beyond basic lipid production.^[42] Depletion of GGPP disrupts osteoclast function, leading to imbalances in bone resorption and remodeling that contribute to conditions like osteoporosis, as geranylgeranylation is required for the activation and survival of these bone-degrading cells.^[43] Recent research as of 2025 has further elucidated GGPP's role in hepatic lipid accumulation, where it promotes metabolic dysfunction-associated steatohepatitis (MUO) by facilitating the prenylation of Perilipin4, leading to pathological lipid droplet expansion and insulin resistance. Additionally, the GGPP branch of the mevalonate pathway is required for chemoresistance in TP53-mutant acute myeloid leukemia (AML).^[44]^[45] This role underscores GGPP's influence on skeletal homeostasis, with inhibitors mimicking its scarcity often used therapeutically to suppress excessive bone loss.^[46] In Drosophila melanogaster, GGPP-derived isoprenoids facilitate germ cell migration during embryogenesis by enabling the geranylgeranylation of guidance proteins, which act as chemoattractants to direct primordial germ cells toward the somatic gonad.^[47] Mutations disrupting GGPP production, such as those in downstream transferases, result in misguided germ cells that fail to coalesce properly, highlighting its specific physiological necessity in this developmental process.^[48] In bacteria and archaea, GGPP is indispensable for membrane lipid synthesis, particularly in archaea where it forms the ether-linked isoprenoid chains of glycerol diphytanyl glycerol tetraethers (GDGTs) and archaeols, conferring extremophile stability to cytoplasmic membranes.^[49] Archaeal geranylgeranyl reductases further saturate these GGPP-derived lipids, adapting membranes to harsh environments like high temperatures or acidity, while bacterial homologs support similar polyisoprenoid assembly in select species.^[50] Disease implications of GGPP dysregulation include statin-induced myopathy in humans, where inhibition of the mevalonate pathway depletes GGPP, triggering skeletal muscle atrophy through myostatin overexpression and impaired protein prenylation.^[51] Therapeutically, inhibitors of geranylgeranyl diphosphate synthase (GGDPS) target cancer by blocking GGPP-mediated Rho GTPase signaling, which disrupts cell proliferation, migration, and survival in tumors reliant on these pathways. As of 2025, specific GGDPS inhibitors like RAM2061 have shown anti-osteoclastic effects by disrupting Rho GTPase geranylgeranylation, and GGPP has been implicated in promoting profibrotic factors in cardiac fibrosis.^[52]^[53]^[54] Such inhibitors induce apoptosis in cancer cells more selectively than broad mevalonate blockers, offering potential for oncology applications.^[55]

Other prenyl pyrophosphates

Dimethylallyl pyrophosphate (DMAPP), the C5 starter unit in the isoprenoid series, functions as the initial allylic substrate for chain elongation, initiating the formation of longer prenyl pyrophosphates through condensation reactions.^[56] Geranyl pyrophosphate (GPP), a C10 analog, arises from the head-to-tail addition of one isopentenyl pyrophosphate (IPP) unit to DMAPP and serves as the key precursor for monoterpenes, which are typically volatile compounds contributing to plant signaling, defense, and pollinator attraction.^[57] Farnesyl pyrophosphate (FPP), the C15 extension, forms by further IPP condensation to GPP and acts as a central intermediate for sesquiterpene biosynthesis as well as cholesterol production in animals.^[58] This structural progression—from DMAPP (C5) to GPP (C10), FPP (C15), and ultimately geranylgeranyl pyrophosphate (GGPP, C20)—occurs via successive trans-configured IPP additions catalyzed by specific prenyl synthases, yielding linear allylic chains that increase in hydrophobicity and length.^[59] As chain length extends, functional roles shift from volatile, short-range signaling molecules derived from GPP and FPP to more stable, structural elements in cellular membranes and proteins supported by longer chains like GGPP.^[60] In protein prenylation, FPP and GGPP exhibit distinct roles: FPP is the preferred substrate for farnesyltransferase (FTase), which attaches the C15 group to cysteine residues in CaaX motifs (where a is typically aliphatic and X is serine, methionine, or others), facilitating moderate membrane anchoring in proteins such as Ras GTPases.^[25] Conversely, GGPP is utilized by geranylgeranyltransferase I (GGTase I) for attaching the bulkier C20 moiety to CaaX motifs where the X residue is typically leucine, providing enhanced hydrophobicity and membrane affinity compared to farnesylation.^[61]^[62] These enzymes display high substrate specificity, with FTase showing a strong preference for FPP over GGPP and GGTase I favoring GGPP, ensuring targeted lipid modifications that influence protein localization and signaling.^[63]

Derived terpenoids

Geranylgeranyl pyrophosphate (GGPP) serves as a central precursor for the biosynthesis of diverse terpenoids, particularly diterpenoids (C20) and higher-order polymers like tetraterpenoids (C40), through enzymatic cyclization, condensation, and modification pathways.^[64] These derived compounds play critical roles in plant growth, defense, human nutrition, and medicine, with GGPP's linear C20 isoprenoid chain providing the foundational scaffold for structural complexity.^[65] Among diterpenes, taxol (paclitaxel), a potent anticancer agent used in chemotherapy, is biosynthesized from GGPP in yew trees via the cyclization to taxa-4(5),11(12)-diene by taxadiene synthase, followed by multiple oxidations and acylations to form the taxane core.^[66] This pathway highlights GGPP's role in producing pharmacologically significant natural products, with over 19 enzymatic steps leading to taxol's bioactive structure.^[67] GGPP also contributes to precursors of retinol (vitamin A), an essential nutrient for vision and immune function, through the carotenoid pathway where beta-carotene, derived from GGPP condensation, is cleaved to retinal and reduced to retinol.^[68] Gibberellins, a class of plant hormones regulating stem elongation, seed germination, and flowering, are synthesized from GGPP in plants and fungi. The pathway begins with the cyclization of GGPP to ent-copalyl diphosphate by copalyl diphosphate synthase, followed by further cyclization to ent-kaurene by kaurene synthase, and subsequent oxidations yielding active forms like GA1 and GA3.^[36] This ent-kaurene route is conserved across species, with GGPP serving as the universal diterpenoid starter unit essential for gibberellin-mediated developmental processes.^[69] Carotenoids, vital pigments for photosynthesis and antioxidants, arise from the head-to-head dimerization of two GGPP molecules to form phytoene, catalyzed by phytoene synthase, with subsequent desaturations producing lycopene and cyclizations yielding beta-carotene.^[70] Beta-carotene, a provitamin A carotenoid abundant in fruits and vegetables, exemplifies GGPP's contribution to human health via dietary precursors, while lycopene provides red coloration and protective roles against oxidative stress in plants.^[71] Other notable GGPP-derived terpenoids include tocopherols (vitamin E forms), where GGPP is reduced to phytyl pyrophosphate by geranylgeranyl reductase before prenylation of homogentisate to form the chromanol ring, supporting antioxidant defense in membranes.^[72] Tocotrienols, unsaturated vitamin E variants, incorporate the full geranylgeranyl chain directly from GGPP.^[73] These examples underscore GGPP's versatility as a branch point in terpenoid metabolism.^[74]

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Jan 17, 2023 · These proteins play key roles in signalling pathways, cytoskeletal regulation and intracellular transport, and in the absence of the prenylation ...
[44]
Role of Metabolism in Bone Development and Homeostasis - MDPI
GGPP plays an important role in the activation of osteoclasts in bone formation and resorption [50,51].
[45]
Geranylgeraniol Application in Human Osteoblasts and Osteoclasts ...
Jun 8, 2023 · The effect of geranylgeraniol (GGOH) on human osteoblast and osteoclast activities suppressed by zoledronate was investigated in this study.Missing: mammals cholesterol
[46]
Isoprenoids Control Germ Cell Migration Downstream of HMGCoA ...
Our data strongly suggest that a geranylgeranylated protein common to vertebrates and invertebrates mediates germ cell attraction downstream of HMGCoAr. The ...Results · Mutations In Fpps And Qm... · The Isoprenoid Branch Of The...
[47]
Germ Cell Specification and Migration in Drosophila and beyond
Consistent with a role of geranylgeranylation, embryos deficient in Geranylgeranyl Transferase type I (GTT1) also display germ cell migration defects. These ...Missing: pyrophosphate | Show results with:pyrophosphate
[48]
Biosynthesis of archaeal membrane ether lipids - Frontiers
This review describes the current knowledge of the biosynthetic pathway of archaeal ether lipids; insights on the stability and robustness of archaeal lipid ...
[49]
Unraveling the multiplicity of geranylgeranyl reductases in Archaea
The multiplicity of geranylgeranyl reductases (GGRs) in archaeal genomes has been correlated with the saturation of polyterpenes.
[50]
Statins induce skeletal muscle atrophy via GGPP depletion ...
Oct 9, 2020 · Simvastatin promotes myostatin expression in both skeletal muscle and brown adipose tissue through inhibiting GGPP production.
[51]
Structural Insight into Geranylgeranyl Diphosphate Synthase ... - NIH
Protein geranylgeranylation is a posttranslational modification critical for the proper localization and function of certain classes of membrane-associated ...
[52]
Geranylgeranyl diphosphate synthase inhibition induces apoptosis ...
Mar 16, 2017 · Both GGPP and FPP partially rescued the effects of zoledronate. Co-treatment with DGBP and zoledronate was antagonistic. To further assess the ...
[53]
Isoprenoids and Protein Prenylation: Implications in the ...
In the isoprenoid pathway, the addition of a third IPP unit to FPP forms the 20-carbon isoprenoid molecule, geranylgeranyl pyrophosphate (GGPP), catalyzed by ...
[54]
Structure and Dynamics of the Isoprenoid Pathway Network
In this review, we summarize our current knowledge of the topology of the plant isoprenoid pathway network and its regulation at the gene expression level ...
[55]
Increasing the intracellular isoprenoid pool in Saccharomyces ...
Jun 17, 2017 · IPP and DMAPP are used as basic subunits by prenyltransferases (PTs), which catalyze sequential reactions to synthesize geranyl diphosphate C10 ...
[56]
Regulation of product chain length by isoprenyl diphosphate ...
Avian FPS catalyzes the sequential chain elongations of DMAPP to GPP and GPP to FPP. ... FPP when chain elongation was initiated with IPP and DMAPP. The ...
[57]
Adaptation of hydroxymethylbutenyl diphosphate reductase enables ...
Mar 12, 2020 · Short-chain isoprenoids (C5, C10, and some C15 compounds) are volatile under physiological conditions, and their functions are generally not ...Missing: diterpenes | Show results with:diterpenes
[58]
Protein prenylation and human diseases
Apr 11, 2015 · The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway.
[59]
Farnesylation or geranylgeranylation? Efficient assays for testing ...
The mutant proteins and the wildtype proteins treated with FTI mislocalized and accumulated in the nucleus. ... The effect of farnesylation or geranylgeranylation ...
[60]
Biosynthesis of the highly oxygenated tetracyclic core skeleton ... - NIH
Mar 15, 2024 · The biosynthesis of Taxol is presumed to originate from the cyclization of geranylgeranyl diphosphate (GGPP) (the common precursor of ...
[61]
Taxol biosynthesis: Taxane 13α-hydroxylase is a cytochrome P450 ...
The initial steps in the biosynthesis of Taxol involve the cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene (25, 26) followed by ...Missing: pyrophosphate | Show results with:pyrophosphate
[62]
Cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)
Apr 14, 1995 · The first dedicated step in taxol biosynthesis is the conversion of the universal diterpenoid precursor geranylgeranyl diphosphate to taxa-4(5),11(12)-diene.
[63]
Restoring the Taxol biosynthetic machinery of Aspergillus terreus by ...
Aug 8, 2019 · The putative Taxol biosynthetic pathway in fungi requires about 19 enzymatic steps starting from the precursor geranylgeranyl diphosphate (GGPP) ...
[64]
Selective biosynthesis of retinol in S. cerevisiae - PMC
Mar 12, 2022 · In order to efficiently produce retinol at high purity, the precursor and NADPH supply was first enhanced to improve retinoids accumulation in the S. ...
[65]
Tailored biosynthesis of gibberellin plant hormones in yeast
The initial steps of gibberellin biosynthesis from geranylgeranyl diphosphate (GGPP) to GA12-aldehyde are similar in fungi and plants. Cyclization of GGPP into ...
[66]
Several geranylgeranyl diphosphate synthase isoforms supply ...
Phytoene synthase (PSY) converts GGPP into phytoene, the first committed intermediate of the carotenoid pathway. Here we used biochemical, molecular, and ...
[67]
Carotenoid Biosynthesis and Regulation in Plants – AOCS
The first committed step in carotenoid biosynthesis is the condensation of two molecules of GGPP by phytoene synthase (PSY) to form phytoene (Fig. 1). GGPP ...
[68]
Vitamin E Biosynthesis and Its Regulation in Plants - PMC - NIH
Dec 25, 2017 · PPP is the lipophilic biosynthetic precursor of tocopherols, while GGPP is the one for tocotrienols, as is SPP for PC-8, and THGGPP for ...
[69]
Vitamin E biosynthesis: functional characterization of the monocot ...
The biosynthesis of the tocotrienol and tocopherol forms of vitamin E is initiated by prenylation of homogentisate. Geranylgeranyl diphosphate (GGDP) is the ...Missing: GGPP | Show results with:GGPP
[70]
Several geranylgeranyl diphosphate synthase isoforms supply ...
Feb 16, 2021 · The three tomato GGPPS isoforms found to localise in plastids (SlG1, 2 and 3) exhibit similar kinetic parameters. Gene expression analyses ...