Dicarboxylate / 4-hydroxybutyrate cycle

The dicarboxylate / 4 Hydroxybutyratzyklus is a biochemical substance cycle, it some Archaea allowed, carbon dioxide (CO ₂ ), in the form of bicarbonate (HCO ₃ ^- to,) assimilate . The cycle can be divided into two halves: First, a molecule of succinyl-CoA is formed from acetyl-CoA , a molecule of carbon dioxide and bicarbonate . In the second part, two molecules of acetyl-CoA are formed from 4-hydroxybutyrate , one of which is used for the next run. This is why the cycle owes its name to the fact that dicarboxylic acids are formed as the first intermediates and 4-hydroxybutyrate later.

Occurrence

The metabolic pathway was originally demonstrated in the hyperthermophilic Archaeon Ignicoccus hospitalis of the Crenarchaeota department . I. hospitalis is the host of the obligatory parasite Nanoarchaeum equitans , also an archaeon . I. hospitalis lives chemolitoautotroph under anaerobic conditions.

The dicarboxylate / 4-hydroxybutyrate cycle was also detected in Thermoproteus neutrophilus , a strictly anaerobic archaeon, and Pyrolobus fumarii , a facultative aerobic archaeon. The former belongs to the order Thermoproteales , the latter to the Desulfurococcales , both representatives of the Crenarchaeota.

biochemistry

Schematic representation of the dicarboxylate / 4-hydroxybutyrate cycle. The eponymous intermediates are shown. Please also note the running text.

Starting from acetyl-CoA , CO ₂ is assimilated to pyruvate by an oxygen-sensitive pyruvate synthase , whereby reduction equivalents are required. Probably these come from reduced ferredoxins . Pyruvate is then converted to phosphoenolpyruvate (PEP) using ATP , which catalyzes a pyruvate: water dikinase. A molecule of bicarbonate then reacts with PEP to form oxaloacetate through an archean PEP carboxylase.

Oxaloacetate is converted to succinyl-CoA analogously in the reductive citric acid cycle via L - malate , fumarate , succinate . This consumes ATP and other reduction equivalents. The cycle owes half of its name to these isolable dicarboxylic acids. Succinyl-CoA is converted into 4-hydroxybutyrate by a succinyl-CoA reductase and a succinate semialdehyde reductase with consumption of further reducing equivalents.

4-Hydroxybutyrate is then converted to 4-hydroxybutyryl-CoA through several enzymatic reactions. From this, through the key enzyme of the cycle, 4-hydroxybutyryl-CoA dehydratase, crotonyl-CoA is created . The hydratase, a 4Fe-4S and FAD -containing enzyme catalyzes the release of water through a Ketylradikalmechanismus. Further catalytic reactions finally transform this into acetoacetyl-CoA via 3-hydroxybutryryl-CoA . An acetoacetyl-CoA β- ketothiolase finally cleaves acetoacetyl-CoA into two molecules of acetyl-CoA, thereby closing the cycle.

The balance for the formation of one molecule of acetyl-CoA is:

${\displaystyle \mathrm {CO_{2}+HCO_{3}^{-}+6\ Fd_{red}+NAD(P)H/H^{+}+3\ ATP+CoA\rightarrow \ } }$ ${\displaystyle \mathrm {Acetyl{\text{-}}CoA++6\ Fd_{ox}+4\ NAD(P)^{+}+ADP+2\ AMP+PP_{i}+3\ P_{i}} }$

Acetyl-CoA is then usually obtained by fixing a further molecule of CO ₂ and consuming reducing equivalents, e.g. B. Ferredoxin (Fd) and ATP converted to glyceraldehyde-3-phosphate . This can then be further metabolized in the carbohydrate metabolism.

As a result, the overall balance for the formation of one molecule of glyceraldehyde-3-phosphate (GAP) is:

${\displaystyle \mathrm {2\ CO_{2}+HCO_{3}^{-}+8\ Fd_{red}+2\ NAD(P)H/H^{+}+5\ ATP\rightarrow \ } }$ ${\displaystyle \mathrm {GAP+8\ Fd_{ox}+2\ NAD(P)^{+}+2\ ADP+3\ AMP+PP_{i}+5\ P_{i}} }$

Biological importance

This metabolic pathway is the last discovered pathway for CO ₂ fixation and is similar to the 3-hydroxypropionate / 4-hydroxybutyrate cycle . However, the formation of succinyl-CoA takes place via dicarboxylic acids; from 4-hydroxybutyrate onwards, the two cycles correspond again to a large extent.

The structure of a phosphorylated triosis , GAP, is energetically somewhat cheaper than the Calvin cycle : eight ATP equivalents are required (AMP counts twice). Balance Calvin Cycle:

${\displaystyle \mathrm {3\ CO_{2}+6\ NAD(P)H/H^{+}+9\ ATP{\xrightarrow {Calvin-Zyklus}}GAP+6\ NAD(P)^{+}+9\ ADP+8\ P_{i}} }$

It should be noted, however, that with the Calvin cycle some energy (and reduction equivalents) are always lost due to the photorespiration that occurs . As a result, the ATP and NAD (P) consumption given in the equation applies under optimal and not under the prevailing conditions in our oxygen-rich atmosphere.

Because of the numerous oxygen-sensitive iron-sulfur proteins and ferredoxins involved, this cycle only takes place under strictly anaerobic or microaerobic conditions. The metabolic pathway is possibly limited to only a few Crenarchaeota . Whether this is one of the first autotrophic metabolic pathways is still being discussed.

literature

• Huber, H. et al . (2008): A dicarboxylate / 4-hydroxybutyrate autotrophic carbon assimilation cycle in the hyperthermophilic Archaeum Ignicoccus hospitalis . In: Proc Natl Acad Sci USA 105 (22); 7851-7856; PMID 18511565 ; PMC 2409403 (free full text)

Individual evidence

1. ↑ Podar, M. et al . (2008): A genomic analysis of the archaeal system Ignicoccus hospitalis-Nanoarchaeum equitans . In: Genome Biol 9 (11); R158; PMID 19000309 ; PMC 2614490 (free full text).
2. ↑ Ramos-Vera, WH. et al . (2009): Autotrophic carbon dioxide assimilation in Thermoproteales revisited . In: J Bacteriol 191 (13); 4286-4297; PMID 19411323 ; PMC 2698501 (free full text).
3. ^ Berg, IA. et al . (2010b): Study of the distribution of autotrophic CO2 fixation cycles in Crenarchaeota . In: Microbiology 156 (Pt 1); 256-269; PMID 19850614 ; doi: 10.1099 / mic.0.034298-0 .
4. ^ Berg, IA. et al . (2010a): Autotrophic carbon fixation in archaea . In: Nat Rev Microbiol . ; PMID 20453874 ; doi: 10.1038 / nrmicro2365 .