If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: superpathway of demethylmenaquinone-6 biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Quinol and Quinone Biosynthesis → Demethylmenaquinol Biosynthesis → Demethylmenaquinol-6 Biosynthesis|
Some taxa known to possess this pathway include : Haemophilus parainfluenzae
Expected Taxonomic Range: Haemophilus
Menaquinones (MK) and demethylmenaquinones (DMK) are low-molecular weight lipophilic components of the cytoplasmic membrane, found in many bacterial species. These quinones function as a reversible redox component of the electron transfer chain, mediating electron transfer between hydrogenases and cytochromes. Menaquinones have also been implicated in regulation, as they are necessary for sporulation and proper regulation of cytochrome formation in some Gram-positive bacteria [Farrand73, Farrand74].
Most aerobic Gram-negative bacteria contain ubiquinone as the sole quinone, while most aerobic Gram-positive bacteria contain menaquinone and/or demethylmenaquinones as the main quinone. However, most of the anaerobic bacteria, regardless whether they are Gram-negative or Gram-positive, contain menaquinone or demethylmenaquinone as their main quinones. Some facultatively anaerobic bacteria, such as Escherichia coli, contain ubiquinone, menaquinone, and demethylmenaquinone, which they use under different growth conditions [Meganathan01a]. The main difference between these quinone molecules is their redox potential. For example, the redox potential for ubiquinone, demethylmenaquinone, and menaquinone has been measured as +112 mv, +36 mv, and -74 mv, respectively, in the bacterium Haemophilus parainfluenzae [Hollander76].
Menaquinones are considered a vitamin (vitamin K2), since they are essential for animals, mostly for the posttranslational modification of certain proteins required for blood coagulation. Animals can not synthesize menaquinones, but usually receive a sufficient amount from bacteria growing in their intestines. In the absence of menaquinone or the related compound phylloquinone (vitamin K1) which is synthesized in plants, animals suffer from hemorrhage [Dam35]. Menaquinone was first isolated from putrefied fish meal by McKee in 1939 [Doisy40], and its structure resolved in 1958 [Isler58].
The biosynthesis of menaquinones is essentially identical to that of demethylmenaquinones, with one additional step, comprising the addition of a methyl group to the naphthoquinone ring. Many bacterial species do not have this methylase and produce demethylmenaquinone as their sole quinone [Collins81].
All three quinones are synthesized from chorismate, an intermediate of aromatic amino acid biosynthesis. However, the pathways of (demethyl)menaquinone synthesis diverts from that for ubiquinones early on. Most organisms synthesize their menaquinones via isochorismate, although some organisms, including Helicobacter pylori, Campylobacter jejuni, Streptomyces coelicolor and Thermus thermophilus, synthesize menaquinones in alternative pathways, via futalosine or 6-amino-6-deoxyfutalosine [Hiratsuka08, Li11, Goble13].
About This Pathway
In this pathway menaquinone is synthesized from chorismate via isochorismate. In a series of reactions, isochorismate is converted to the two-ring compound 1,4-dihydroxy-2-naphthoate via several intermediates that include 2-succinylbenzoate. At this point a prenyltransferase enzyme attaches a polyprenyl tail to form a demethylmenaquinone, which can be converted to a menaquinone by a dedicated methylase.
Demethylquinones were first discovered in Haemophilus parainfluenzae [Lester64]. The main form was demethylmenaquinone-6 (DMK-6), although lesser amounts of DMK-5 and DMK-7 were also detected. Additional studies found that DMK-6 is involved in respiration in Haemophilus parainfluenzae, and could mediate electron transfer between NADH and succinate, similar to ubiquinone (Q). In addition, DMK-6 could act as a mediator in fumarate reduction, similar to menaquinone (MK). Thus, in contrast to Q and MK, DMK acts equally well in succinate respiration and in fumarate reduction [Hollander76].
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