Precursors ubiquinone pathway

The shikimate pathway is the major route in the biosynthesis of ubiquinone, menaquinone, phyloquinone, plastoquinone, and various colored naphthoquinones. The early steps of this process are common with the steps involved in the biosynthesis of phenols, flavonoids, and aromatic amino acids. Shikimic acid is formed in several steps from precursors of carbohydrate metabolism. The key intermediate in quinone biosynthesis via the shikimate pathway is the chorismate. In the case of ubiquinones, the chorismate is converted to para-hydoxybenzoate and then, depending on the organism, the process continues with prenylation, decarboxylation, three hydroxy-lations, and three methylation steps. - ... 

DUVOLD, T., CALI, P., BRAVO, J.-M., ROHMER, M., Incorporation of 2-C-methyl-D-erythritol, a putative isoprenoid precursor in the mevalonate-independent pathway, into ubiquinone and menaquinone of Escherichia coli, Tetrahedron Lett., 1997, 38, 6181-6184. 

Terpenoids are derived from the cytosolic mevalonate pathway or from the plastidial 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway (see also Terpenoid Biosynthesis). Both pathways lead to the formation of the C5 units isopentenyl diphosphate and its allylic isomer dimethylallyl diphosphate, which are the basic terpenoid biosynthesis building blocks (Fig. 1). Although increasing evidence suggests that exchange of intermediates occurs between these compartments, the cytoplasmic mevalonate pathway is generally considered to supply the precursors for the production of sesquiterpenes and triterpenes (including sterols) and to provide precursors for protein prenylation and for ubiquinone and heme-A production in mitochondria. In the plastids, the MEP pathway supplies the precursors for the production of isoprene, monoterpenes, diterpenes (e.g., GAs), and tetraterpenes (e.g., carotenoids). 

Even though E. coli is a very well-studied bacterium, many interesting mechanistic problems in cofactor biosynthesis in this organism remain unsolved. The mechanisms for the formation of the nicotinamide ring of NAD, the pyridine ring of pyridoxal, the pterin system of molybdopterin, and the thiazole and pyrimidine rings of thiamin are unknown. The sulfur transfer chemistry involved in the biosynthesis of lipoic acid, biotin, thiamin and molybdopterin is not yet understood. The formation of the isopentenylpyrophosphate precursor to the prenyl side chain of ubiquinone and menaquinone does not occur by the mevalonate pathway. None of the enzymes involved in this alternative terpene biosynthetic pathway have been characterized. The aim of this review is to focus attention on these unsolved mechanistic problems. 

DMAPP is a precursor of many isoprenoid compounds including carotenoids, sterols, and ubiquinones. IPP isomerase is an essential enzyme in organisms that use the mevalonate pathway to synthesize isoprenoid units, making the enzymes from S. pneumoniae and S. aureus interesting drug targets. 

The long side chain of CoQ has 10 of the 5-carbon isoprenoid units, and is sometimes called CoQk,. It is also called ubiquinone (the quinone found everywhere) because quinones with similar structures are found in all plants and animals. CoQ can be synthesized in the human from precursors derived from carbohydrates and fat. The long isoprenoid side chain is formed in the pathway that produces the isoprenoid precursors of cholesterol. CoQio is sometimes prescribed for patients recovering from a myocardial infarction, in an effort to increase their exercise capacity. 

C7H,o05, Mr 174.15. needles, D. 1.6, mp. 178-180°C, [a]g -157° (H2O), pKg4.15 (14.1 °C), soluble in water. S. is a widely distributed component of plants and occurs especially in fruits of the star anise (lllicium anisatum, syn. /. religiosum, Illiciaceae Japanese shi-kimi-no-ki). S. is a key intermediate of the so-called shikimic acid pathway which includes the biosynthesis of the aromatic amino acids phenylalanine, tyrosine, and tryptophan. These, in turn, are precursors of numerous alkaloids, flavonoids, and lignans, as well as 4-amino- and 4-hydroxybenzoic acid, gallic acid, tetrahydrofolic acid, ubiquinones, vitamin K, and nicotinic acid. The synthetic racemate melts at 191-192 °C. 

Aromatic biosynthesis, aromatizatioa biosynthesis of compounds containing the benzene ring system. The most important mechanisms are 1. the shi-kimate/chorismate pathway, in which the aromatic amino acids, L-phenylalanine, L-tyrosine and L-trypto-phan, 4-hydroxybenzoic acid (precursor of ubiquinone), 4-aminobenzoie acid (precursor of folic acid) and the phenylpropanes, including components of lignin, cinnamic acid derivatives and flavonoids are synthesized and 2. the polyketide pathway (see Polyke-tides) in which acetate molecules are condensed and aromatic compounds (e.g. 6-methylsalicylic acid) are synthesized via poly-fl-keto acids. Biosynthesis of flavonoids (e.g. anthocyanidins) can occur by either pathway. 

The metabolic pathway responsible for biosynthesis of aromatic amino acids and for vitamin-like derivatives such as folic acid and ubiquinones is a major enzyme network in nature. In higher plants this pathway plays an even larger role since it is the source of precursors for numerous phenylpropanoid compounds, lignins, auxins, tannins, cyano-genic glycosides and an enormous variety of other secondary metabolites. Such secondary metabolites may originate from the amino acid end products or from intermediates in the pathway (Fig. 1). The aromatic pathway interfaces with carbohydrate metabolism at the reaction catalyzed by 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase, the condensation of erythrose-4-phosphate and PEP to form... 

The aromatic core of the CoQn molecule is derived from the shikimate pathway, which starts with the condensation of erythrose-4-phosphate (E4P) and phosphoe-nolpymvate (PEP). The shikimate pathway leads to the production of the aromatic intermediate chorismate, a precursor for several essential aromatic molecules including aromatic amino acids and folate, which is converted to para-hydroxybenzoic acid (PHB) by the chorismate lyase UbiC. PHB, the first committed intermediate to ubiquinone biosynthesis, is then prenylated with an isoprenoid of varying length, depending on the species (Fig. 15.2). 

The cytosolic MVA pathway provides precursors for sterols and the side chain of ubiquinone, whereas synthesis of monoterpenes, certain sesquiterpenes, diterpenes, carotenoids, and the side chains of chlorophylls and plastoquinone is carried out in plastids [12]. Cross-talk occurs between the MVA and MEP pathways, and appears to be mainly unidirectional from plastids to cytosol, although limited import of intermediates into the plastid has been observed [13]. 

Bacterial isoprenoid synthesis - the Rohmer pathway Current biosynthetic evidence indicates that the steps from IPP to isoprenoids in Eubacteria are the same as those in eukaryotes [62-69] (see [70-73] for literature). Especially the incorporation of C-labeled precursors into prokaryotic hopanoids, sterol surrogates in bacterial membranes (see [73] and literature cited therein), or into ubiquinone-8 [70] has revealed that the classic pathway of IPP formation starting from acetyl-CoA via acetoacetyl-CoA, HMG-CoA, MVA, MVA-P, and MVA-PP does not exist in a great variety of bacteria, including E. coli Zymomonas mobilis, Methylobacterium organophilum, Rhodopseudomonas palustris, R. acidophila, Acetobacter aceti ssp. xylinum, but also in the thylakoids of the cyanobacterium Synechocystis sp. [74]. 

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