Terpenoid Metabolism

The 20,000+ terpenoids found in animals, plants, bacteria, fungi, and archaea are all based on multiples of the 5-carbon isoprene subunit. This is due to biosynthetic pathways that utilize isopentenyl pyrophosphate (IPP) or its isomer dimethylallyl pyrophosphate (DMAPP) as isoprene building blocks for condensation reactions.

Depending on the biological organism and the terpenoid, two different metabolic pathways exist for the biosynthesis of isopentenyl pyrophosphate:
the mevalonate pathway and
the non-mevalonate or methyl D- erythritol 4-phosphate (MEP) pathway.

The mevalonate pathway starts with the formation of acetoacetyl CoA from two molecules of acetyl CoA via Claisen condensation by acetyl-CoA C-acetyltransferase. Acetoacetyl CoA is then condensed with a third molecule of acetyl CoA in an aldol-like reaction catalyzed by hydroxymethylglutaryl-CoA synthase, followed by hydrolysis, to give the metabolite 3-hydroxy-3-methylglutaryl-CoA. In the third step, NADPH-dependent reduction of the thioester group catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase yields mevalonate. Mevalonate is phosphorylated at the primary hydroxy group by mevalonate kinase to form mevalonate-5-phosphate, which undergoes a second kinase reaction to form mevalonate-5-pyrophosphate. A final phosphorylation at the tertiary hydroxyl group, catalyzed by mevalonate-5-diphosphate decarboxylase, with the simultaneous loss of carbon dioxide and phosphate results in 3-isopentenyl pyrophosphate.

In contrast to the extensively studied and historic mevalonate pathway, the MEP pathway was only discovered in the 1990∅s and is used by bacteria, algae, and chloroplasts. 1 The first step consists of the 1-deoxy- D -xylulose-5-phosphate synthase-catalyzed coupling of pyruvate with D -glyceraldehyde-3-phosphate to give 1-deoxy- D -xylulose-5-phosphate (DOXP) with concurrent loss of carbon dioxide. Next, an NADPH-dependent rearrangement and reduction reaction is catalyzed by deoxyxylulose-5-phosphate reductoisomerase to produce methyl- D -erythritol 4-phosphate (MEP). MEP is conjugated with cytidine triphosphate (CTP) to produce 4-diphosphocytidyl-2C-methyl- D -erythritol. This intermediate undergoes additional phosphorylation at the 2-position of the erythritol moiety (4-diphosphocytidyl-2C-methyl- D -erythritol 2-phosphate) with subsequent enzymatic cylization and loss of cytidine monophosphate. This metabolite is finally converted to isopentenyl pyrophosphate by the action of two enzymes that reduce the cyclodiphosphate intermediate to a diphosphate and subsequent pyrophosphate.

Another important step in the biosynthesis of terpenoids is the isomerization of isopentenyl pyrophosphate to dimethylallyl pyrophosphate catalyzed by isopentenyl pyrophosphate isomerase. These two fundamental metabolites are joined to form geranyl pyrophosphate (GPP). GPP can be elongated with another molecule of isopentenyl pyrophosphate to farnesyl pyrophosphate (FPP) through sequencial condensation by farnesyl pyrophosphate synthetase. Terpenoids with up to 5 isoprenoid units (25 carbons) can be synthesized in this manner, while structures with higher numbers of carbon atoms are formed by dimerization of the corresponding building blocks.
Reference:
1. Hunger, W.N., et al., Structure and reactivity in the non-mevalonate pathway of isoprenoid biosynthesis. Biochem. Soc., Trans ., 31 , 537 (2003).

Mevalonate Pathway

Product #

Image

Description

Biochem/physiol Actions

Add to Cart

79849   (±)-Mevalonic acid 5-phosphate lithium salt hydrate 95% (TLC) Metabolite of the mevalonate pathway, which plays a key role in the biosynthesis of sterols, dolichol, heme and ubiquinone. Of interest for research in the disease areas oncology, autoimmune diseases, artherosclerosis and Alzheimer disease, as well as for inherited deficiencies of mevalonate kinase.
94259 (±)-Mevalonic acid 5-pyrophosphate tetralithium salt ≥80% (qNMR) Metabolite of the mevalonate pathway, which plays a key role in the biosynthesis of sterols, dolichol, heme and ubiquinone. Of interest for research in the disease areas oncology, autoimmune diseases, artherosclerosis and Alzheimer disease, as well as for inherited deficiencies of mevalonate kinase. Mevalonic acid 5-pyrophosphate was shown to elevate ubiquinone levels in rat liver tissues.
M4667 (±)-Mevalonolactone ~97% (titration)  
68519 (R)-(−)-Mevalonolactone ≥90.0% (GC) Classical enantiomerically pure metabolite in biosynthetic pathways leading to sterols, terpenes, carotenoids, and other natural products.
07841 (R)-Mevalonic acid 5-phosphate lithium salt 95% (TLC) Metabolite of the mevalonate pathway, which plays a key role in the biosynthesis of sterols, dolichol, heme and ubiquinone. Of interest for research in the disease areas oncology, autoimmune diseases, artherosclerosis and Alzheimer disease, as well as for inherited deficiencies of mevalonate kinase.
77631 (R)-Mevalonic acid 5-pyrophosphate tetralithium salt ≥95% (TLC) Metabolite of the mevalonate pathway, which plays a key role in the biosynthesis of sterols, dolichol, heme and ubiquinone. Of interest for research in the disease areas oncology, autoimmune diseases, artherosclerosis and Alzheimer disease, as well as for inherited deficiencies of mevalonate kinase.
50838 (R)-Mevalonic acid lithium salt ≥93.0% (qNMR) Mevalonic acid, is an intermediate in the mevalonate pathway, producing terpenes and steroids. This function provides treatment options metabolic disorders , R-mevalonate accumulates in patients with the autosomal recessively inherited mevalonic acidurias, an inborn error of cholesterol and nonsterol isoprene biosynthesis.
90469 (RS)-Mevalonic acid lithium salt ≥96.0% (GC) Metabolite of the mevalonate pathway, which plays a key role in the biosynthesis of sterols, dolichol, heme and ubiquinone. Of interest for research in the disease areas oncology, autoimmune diseases, artherosclerosis and Alzheimer disease, as well as for inherited deficiencies of mevalonate kinase.
44714 (S)-Mevalonic acid lithium salt ≥96.0% (GC) Metabolite of the mevalonate pathway, which plays a key role in the biosynthesis of sterols, dolichol, heme and ubiquinone. Of interest for research in the disease areas oncology, autoimmune diseases, artherosclerosis and Alzheimer disease, as well as for inherited deficiencies of mevalonate kinase.
H6132 DL-3-Hydroxy-3-methylglutaryl coenzyme A sodium salt hydrate ≥90% (HPLC) DL-3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) is a substrate used to study the specificity and kinetics of the enzyme 3-hydroxyl-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase. HMG-CoA is the key intermediate in the biosynthsis of terpenes, cholesterol, and ketone bodies. Its metabolism is the target of statin drugs used to control cholesterol levels.
A2181 Acetyl coenzyme A lithium salt ≥93% (HPLC) Acetyl-CoA is an essential cofactor and carrier of acyl groups in enzymatic acetyl transfer reactions. It is formed either by the oxidative decarboxylation of pyruvate in mitochondria, by the oxidation of long-chain fatty acids, or by the oxidative degradation of certain amino acids. Acetyl-CoA is the starting compound for the citric acid cycle (Kreb′s cycle). It is also a key precursor in lipid biosynthesis, and the source of all fatty acid carbons. Acetyl-CoA positively regulates the activity pyruvate carboxylase. It is a precursor of the neurotransmitter acetylcholine. Histone acetylases (HAT) use Acetyl-CoA as the donor for the acetyl group use in the post-translational acetylation reactions of histone and non-histone proteins.
Alterations in the gene encoding acetyl-CoA have been linked to Alzheimer′s disease and mild cognitive impairment. Defects in the gene cause myasthenic syndrome associated with episodic apnea.
A2056 Acetyl coenzyme A sodium salt ≥93% (HPLC), powder Acetyl-CoA is an essential cofactor and carrier of acyl groups in enzymatic acetyl transfer reactions. It is formed either by the oxidative decarboxylation of pyruvate in mitochondria, by the oxidation of long-chain fatty acids, or by the oxidative degradation of certain amino acids. Acetyl-CoA is the starting compound for the citric acid cycle (Kreb′s cycle). It is also a key precursor in lipid biosynthesis, and the source of all fatty acid carbons. Acetyl-CoA positively regulates the activity pyruvate carboxylase. It is a precursor of the neurotransmitter acetylcholine. Histone acetylases (HAT) use Acetyl-CoA as the donor for the acetyl group use in the post-translational acetylation reactions of histone and non-histone proteins.
658650 Acetyl-1,2-13C2 coenzyme A lithium salt 99 atom % 13C, 95% (CP)  
18629 Isopentenyl phosphate dilithium salt ≥95.0% (TLC) Isopentenyl monophosphate is phosphorylated into isopentenyl pyrophosphate at very low rates.
I0503 Isopentenyl pyrophosphate triammonium salt solution 1 mg/mL in methanol (:aqueous 10 mM NH4OH (7:3)), ≥95% (TLC)  
00297 Isopentenyl pyrophosphate trilithium salt ≥95.0% (TLC) Intermediate in terpene biosynthesis
591270 Mevalonolactone-(methyl-13C) 99 atom % 13C  
492469 Mevalonolactone-1-13C 99 atom % 13C, 98% (CP)  
486604 Mevalonolactone-2-13C 99 atom % 13C, 98% (CP)  
54747 γ,γ-Dimethylallyl phosphate ammonium salt ≥93.0% (TLC)  
69579 γ,γ-Dimethylallyl pyrophosphate ammonium salt ≥93.0% (TLC) Intermediate in terpene biosynthesis
D4287 γ,γ-Dimethylallyl pyrophosphate triammonium salt 1 mg/mL in methanol (:aqueous 10 mM NH4OH (7:3)), ≥90% (TLC) Intermediate in terpene biosynthesis

Non-Mevalonate (MEP/DOXP) Pathway

Product #

Image

Description

Biochem/physiol Actions

Add to Cart

14764 1-Deoxy-D-xylulose ≥80% (TLC) Metabolite of the non-mevalonate pathway, generally found in prokaryotes, as precursor to isoprenoids as well as non-isoprenoids like vitamins. As this pathway is not present in humans, it is of interest for the development of bacterium-specific drugs in the search for treatments of infectious diseases.
13368 1-Deoxy-D-xylulose-5-phosphate sodium salt ≥99.0% (TLC) Metabolite of the non-mevalonate pathway, generally found in prokaryotes, as precursor to isoprenoids as well as non-isoprenoids like vitamins. As this pathway is not present in humans, it is of interest for the development of bacterium-specific drugs in the search for treatments of infectious diseases.
52131 2-C-Methyl-D-erythritol 4-phosphate lithium salt ≥98% (TLC) Metabolite intermediate specific to the non-mevalonate MEP pathway, generally found in prokaryotes, as precursor to isoprenoids as well as non-isoprenoids like vitamins. As this pathway is not present in humans, it is of interest for the development of bacterium-specific drugs in the search for treatments of infectious diseases.
41707 2-C-Methyl-D-erythritol ≥90% (GC) Metabolite of the non-mevalonate MEP pathway, generally found in prokaryotes, as precursor to isoprenoids as well as non-isoprenoids like vitamins. As this pathway is not present in humans, it is of interest for the development of bacterium-specific drugs in the search for treatments of infectious diseases.
G5251 DL-Glyceraldehyde 3-phosphate solution 45-55 mg/mL in H2O Glyceraldehyde 3-phosphate is an intermediate in several metabolic pathways, including glycolysis and gluconeogenesis. It is bactericidal and a potent inhibitor of growth in E. coli.
18629 Isopentenyl phosphate dilithium salt ≥95.0% (TLC) Isopentenyl monophosphate is phosphorylated into isopentenyl pyrophosphate at very low rates.
I0503 Isopentenyl pyrophosphate triammonium salt solution 1 mg/mL in methanol (:aqueous 10 mM NH4OH (7:3)), ≥95% (TLC)  
00297 Isopentenyl pyrophosphate trilithium salt ≥95.0% (TLC) Intermediate in terpene biosynthesis
107360 Pyruvic acid 98% Pyruvic acid reacts with N-acetyl mannosamine by an aldol-type condensation to form sialic acid. Pyruvic acid is a component of commercial red seaweed polysaccharide. In muscle, pyruvic acid (derived from glycogen) is reduced to lactic acid during exertion, which is reoxidized and partially retransformed to glycogen during rest.
490717 Sodium pyruvate-13C3 99 atom % 13C  
490725 Sodium pyruvate-2-13C 99 atom % 13C  
P2256 Sodium pyruvate ReagentPlus®, ≥99%  
792500 Sodium pyruvate anhydrous, free-flowing, Redi-Dri, ReagentPlus®, ≥99%  
54747 γ,γ-Dimethylallyl phosphate ammonium salt ≥93.0% (TLC)  
69579 γ,γ-Dimethylallyl pyrophosphate ammonium salt ≥93.0% (TLC) Intermediate in terpene biosynthesis
D4287 γ,γ-Dimethylallyl pyrophosphate triammonium salt 1 mg/mL in methanol (:aqueous 10 mM NH4OH (7:3)), ≥90% (TLC) Intermediate in terpene biosynthesis

Terpenoids

Product #

Image

Description

Biochem/physiol Actions

Add to Cart

15785 (−)-Menthol puriss., meets analytical specification of Ph. Eur., BP, USP, 98.0-102.0%  
22075 (−)-trans-Caryophyllene ≥98.5% (sum of enantiomers, GC)  
83073 (+)-α-Terpineol analytical standard  
62120 (R)-(+)-Limonene purum, ≥96.0% (sum of enantiomers, GC)  
41043 2,3-Oxidosqualene ≥92.0% (HPLC) 2,3-Oxidosqualene is a substrate of the 2,3-oxidosqualene cyclase lanosterol synthase. 2,3-oxidosqualene cyclase has been shown to be suppressed by a high fat diet and high levels of cholesterol.
94967 2-cis,6-trans-Farnesol ≥95.0% (GC) Farnesol is an acyclic sesquiterpene alcohol, with four possible isomers, the E/E-isomer being the most common in nature. It was found to have different biological functions, for example to act as a quorum-sensing molecule to suppress filamentation in the fungus Candida albicans; and to have antibacterial effects against Staphylococcus aureus, including promotion of potassium ion leakage. Its derivatives are involved in the a-factor mating peptide of the dodecapeptide pheromone found in Saccharomyces cerevisiae. The biological activity of farnesol and FPP analogues are investigated in cancer research. 2-cis,6-trans-Farnesol is a metabolite in the sesquiterpenoid and triterpenoid biosynthesis, a reactant of farnesol 2-isomerase (EC: 5.2.1.9)
94966 2-trans,6-cis-Farnesol ≥95.0% (GC) Farnesol is an acyclic sesquiterpene alcohol, with four possible isomers, the E/E-isomer being the most common in nature. It was found to have different biological functions, for example to act as a quorum-sensing molecule to suppress filamentation in the fungus Candida albicans; and to have antibacterial effects against Staphylococcus aureus, including promotion of potassium ion leakage. Its derivatives are involved in the a-factor mating peptide of the dodecapeptide pheromone found in Saccharomyces cerevisiae. The biological activity of farnesol and FPP analogues are investigated in cancer research.
41111 Ajmalicine ≥98.0% (HPLC) Metabolite in the indole alkaloid biosynthesis (serpentine production); found naturally in various plants such as Rauwolfia spp., Catharanthus roseus, and Mitragyna speciosa. It shows antimicrobial activity, and is used as an anti-hypertensive and sedative.
F6892 Farnesyl pyrophosphate ammonium salt methanol:ammonia solution, ≥95% (TLC) Isoprenoid from the intracellular mevalonate pathway used for prenylation of several low molecular mass G proteins, including Ras.
163333 Geraniol 98%  
56901 Geranyl monophosphate lithium salt ≥95.0% (TLC)  
G6772 Geranyl pyrophosphate ammonium salt 1 mg/mL in methanol (:aqueous 10 mM NH4OH (7:3)), ≥95% (TLC) Intermediate in terpene biosynthesis
76532 Geranyl pyrophosphate lithium salt ≥95.0% (TLC) Metabolite in monoterpenoid biosynthesis, substrate for monoterpene synthases.
G3278 Geranylgeraniol ≥85% (GC) As the pyrophosphate, the metabolic precursor of all diterpenes. Screening in vitro shows this to be a potent and selective agent against Mycobacterium tuberculosis.
G6025 Geranylgeranyl pyrophosphate ammonium salt solution, ≥95% (TLC), ~1 mg/mL in methanol: NH4OH (7:3) Isoprenoid from the intracellular mevalonate pathway used for prenylation of several low molecular weight G proteins, including Ras. Intermediate in terpene biosynthesis.
L9879 Lycopene ≥90%, from tomato Antioxidant micronutrient of tomatoes associated with decreased risk for cancer and cardiovascular disease. Enhances gap juction communication between cells via upregulation of connexin 43 and reduces proliferation of cancer cells in culture. Inhibits cholesterol synthesis and enhances low-density lipoprotein degradation.
18577 Neryl monophosphate lithium salt ≥95.0% (TLC) Monoterpene phosphate
12436 Neryl pyrophosphate lithium salt ≥95.0% (TLC) Metabolite, substrate for monoterpene synthase.
80191 Phytol technical, mixture of isomers (~2/1: trans/cis), ≥90% (sum of enantiomers, GC)  
53675 α-Humulene ≥96.0% (GC)  
22040 β-Carotene ≥97.0% (UV) The most important of the provitamins A, β-carotene can be classified as an antioxidant due to its inhibition of radical initiated peroxidation in vitro. However, in vivo it appears to act either as an antioxidant or a prooxidant depending on cellular environment. It reduces the incidence of many cancers, but enhances lung cancer incidence in smokers.
80720 cis,cis-Farnesol ≥95.0% (GC) Farnesol is an acyclic sesquiterpene alcohol, with four possible isomers, the E/E-isomer being the most common in nature. It was found to have different biological functions, for example to act as a quorum-sensing molecule to suppress filamentation in the fungus Candida albicans; and to have antibacterial effects against Staphylococcus aureus, including promotion of potassium ion leakage. Its derivatives are involved in the a-factor mating peptide of the dodecapeptide pheromone found in Saccharomyces cerevisiae. The biological activity of farnesol and FPP analogues are investigated in cancer research.
72180 cis-Nerolidol ≥96.0% (GC)  
277541 trans,trans-Farnesol 96%  
91356 trans,trans-Farnesyl monophosphate ammonium salt ≥95.0% (TLC) Farnesyl monophosphate is a metabolite in terpenoid backbone biosynthesis. It was shown to activate PPARalpha and PPARbeta/delta reporter gene expression, indicating new potential roles for the oligoprenyl phosphates as potential endogenous modulators of LPA targets.
44270 trans,trans-Farnesyl pyrophosphate ammonium salt ≥95.0% (HPLC) Farnesyl pyrophosphate is a key intermediate in the biosynthesis of more complex sesquiterpenoids, higher terpenoids, and steroids and different biological functions have been discovered for FPP and the corresponding alcohol farnesol. FPP plays an important role in the posttranslational processing of Ras proteins. Mutated forms of Ras are associated with human cancer and are therefore investigated in cancer research.