Coenzyme F420
- Coenzyme F420
- N-( N- { o- [5 - ( 8-hydroxy- 2 ,4- dioxo- 2,3,4,10 - tetra- hydropyrimido [ 4,5-b ] quinoline -10 -yl ) - 5 -deoxy L- ribityl -1 -phospho ] - (S) - lactyl } - γ -L -glutamyl ) - L -glutamate
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Cofactor F420 hot chemical compounds that occur in the cytoplasm of methanogenic archaea, some bacteria and unicellular eukaryotes. It is biochemically by electron transporter, and chemically to Deazaflavine similar to riboflavin. They differ in the length of the polyglutamate chain containing from five to seven Glu residues in the mycobacteria. A member of the group of substances was first isolated in 1972. The chemical structure was elucidated in 1978. The cofactor is named for its strong absorption at lambda max = 420 nm
Chemical Properties
Oxidized F420 absorbs at 420 nm, after absorption of light emitted at 520 nm. At isobestic point at 401 nm, the extinction coefficient has a cofactor of 25.9 mM -1cm -1. After reduction ( F420H2 ) F420 loses its absorption maximum at 420 nm and this shifts to 320 nm, but with a lower extinction coefficient.
Biological Significance
Although F420 has a similar structure as riboflavin or FAD, but in chemical terms, it is more like the Nikotinamiden, such as NADP . The redox potential of -350 mV to F420 is similar to that of it, therefore, NAD (P) s ( -320 mV). F420 only transfers a hydride ion (two electrons and one proton) - as well as NAD or NADP .
The basic structure, the 7,8- Didemethyl -8-hydroxy -5- deazariboflavin -5 ' -phosphate is found in archaea, but also in the Gram-positive eubacteria, such as Streptomyces or Mycobacteria. The cofactor was discovered in the cyanobacterium Anacystis nidulans acutus and in the ( eukaryotic ) green alga Scenedesmus. However, the basic structure varies in those organisms.
F420 is involved in processes of methanogenesis, the reduction of sulphite, the oxygen detoxification and the electron transport in archaea.
It is a cofactor in the synthesis of antibiotics in streptomycetes as well as for the reduction of nitrogen dioxide and PA 824 in mycobacteria, where it is reduced back by the glucose -6 -phosphate dehydrogenase again. PA -824 is an experimental drug for the treatment of tuberculosis.
F420 -dependent enzymes
F420 is often used as an electron carrier in methanogenesis, but he emerges also in other processes:
Tetrahydromethanopterin - dependent enzyme
During methanogenesis - from CO2 - play Tetrahydromethanopterin -dependent enzymes play a central role. The F420 -dependent N5, N10- Methylentetrahydromethanopterin dehydrogenase reduced to Methanopterin Methenyl bound to methylene. This is (reduced ) F420H2 consumed ( see equation 1).
The F420 -dependent N5, N10- Methylentetrahydromethanopterin reductase reduces the consumption of F420H2 bound to Methanopterin methylene continue to methyl ( see equation 2):
F420 -reducing hydrogenase
For the regeneration of oxdierten F420, an enzyme is needed, which is called the F420 -reducing hydrogenase. The enzyme is often either membrane bound or localized sporadically in the cytoplasm.
NADP/F420 oxidoreductase
The transfer of two reducing equivalents from F420H2 to NADP catalyzed by a transhydrogenase, a NADP/F420 oxidoreductase. NADPH is required even in methanogenic bacteria for the synthesis of certain cellular metabolites, but in addition also in NADPH-dependent alcohol dehydrogenases.
Formiatdehydrogenease
Some methanogenic organisms can gain reducing equivalents by oxidation of formic acid. Since the oxidation is accompanied with the reduction of F420, F420 as is regenerated. This enzyme has been purified at Methanobacterium formicicum and expressed in E. coli.
Alcohol dehydrogenase
Isopropanol or ethanol are used by various methanogenic organisms as an alternative source of electrons for the reduction of CO2. So in methanogens isopropanol reduced by an F420 - dependent secondary alcohol consumption among F420 is oxidized to acetone.
Pharmacological significance
In an in silico screening according to F420 -dependent enzymes, a surprisingly large number of candidates are found in M. tuberculosis. Although these enzymes have not been characterized biochemically, they could represent a pharmacological target, as almost no bacteria are present in the intestinal flora with such enzymes, and antibiotics against M. tuberculosis on the basis of inhibition of F420 -dependent enzymes, therefore, hardly any side effects on the intestinal flora had.