3-hydroxypropionate / 4-hydroxybutyrate cycle

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

Occurrence

The metabolic pathway was demonstrated in thermo- acidophilic archaea of the order Sulfolobales (for example Stygiolobus azoricus ), representatives of the Crenarchaeota department . These microorganisms are either microaerophilic or, in the case of Stygiolobus, strictly anaerobic .

It is still open to debate whether the cycle will also operate in mesophilic marine Group-I Crenarchaeota. These are common marine arks that grow in mesophilic conditions.

biochemistry

Schematic representation of the 3-hydroxypropionate / 4-hydroxybutyrate cycle. The intermediates that give it its name and the required cofactors are shown. Please also note the running text.

Starting from acetyl-CoA , malonate semialdehyde is formed in two reaction steps , which is reduced to 3-hydroxypropionate by a malonate semialdehyde reductase. Two molecules of NADPH , one molecule of ATP and one molecule of bicarbonate are required for these reaction steps . 3-Hydroxypropionate is converted into succinyl-CoA via several intermediates; a vitamin B ₁₂ -dependent enzyme, methylmalonyl-CoA mutase, is also involved.

Succinyl-CoA then catalyses a succinate-semialdehyde reductase with consumption of NADPH to form 4-hydroxybutyrate from succinate-semialdehyde. The formation of 4-hydroxybutyrate from 3-hydroxypropionate requires three molecules of NADPH, two molecules of ATP, bicarbonate and another molecule coenzyme A . Finally, 4-hydroxybutyrate is converted into acetoacetyl-CoA , consuming one molecule each of ATP and coenzyme A and NAD ⁺ . This is split into two molecules of acetyl-CoA by an acetoacetyl-CoA β- ketothiolase , so that the cycle closes here and an acetyl-CoA is released.

The overall balance for the formation of one molecule of acetyl-CoA is therefore (without reference to coenzyme A):

${\displaystyle \mathrm {2\ HCO_{3}^{-}+4\ NADPH/H^{+}+4\ ATP} }$ ${\displaystyle \mathrm {\rightarrow \ Acetyl{\text{-}}CoA+4\ NADP^{+}+4\ ADP+4\ P_{i}} }$

Biological importance

This metabolic pathway was only recently discovered and represents a variant of the 3-hydroxypropionate cycle. Up to the formation of succinyl-CoA, the two cycles largely correspond. However, the enzymes involved are not phylogenetically related and seem to have evolved independently of one another.

The cycle also partially coincides with the recently discovered dicarboxylate / 4-hydroxybutyrate cycle , which is also operated by representatives of the Crenarchaeota. The formation of acetoacyl-CoA from succinyl-CoA is identical in both cycles.

The sensitivity to oxygen can be explained by the fact that an involved enzyme, 4-hydroxybutyryl-CoA dehydratase , is sensitive to oxygen.

The acetyl-CoA formed by the cycle can be built up into glyceraldehyde-3-phosphate (GAP) and flow into the building metabolism. Here, further cofactors such. B. Ferredoxin (Fd) is required. The overall balance for the formation of a GAP molecule is thus:

${\displaystyle \mathrm {2\ HCO_{3}^{-}+CO_{2}+5\ NAD(P)H/H^{+}+6\ ATP+2\ Fd_{red}\rightarrow \ } }$

${\displaystyle \mathrm {GAP+5\ NAD(P)^{+}+3\ ADP+3\ AMP+4\ P_{i}+2\ PP_{i}+2\ Fd_{ox}} }$

It is not yet known whether the two molecules, pyrophosphate, will be hydrolyzed or used as an energy source.

It has recently been discussed whether pyruvate is not formed from succinyl-CoA, an intermediate in the cycle. Succinyl-CoA is withdrawn from the circulation, converted to malate or oxaloacetate and finally decarboxylated to pyruvate. To form succinyl-CoA from acetyl-CoA, one and a half rounds of the 3-hydroxypropionate / 4-hydroxybutyrate cycle are required.

The structure of a phosphorylated triosis , GAP, is energetically similar to the metabolic pathway of the Calvin cycle , since new ATP equivalents are also used here (AMP counts twice). In the Calvin cycle, however, more and more energy and reduction equivalents are lost due to the photorespiration that occurs . In addition, the carboxylases involved in bicarbonate fixation have a higher turnover number (28 ss ⁻¹ at 65 ° C) than RuBisCO in the Calvin cycle (5 s ⁻¹ ).

Individual evidence

1. ^ Berg, IA. et al . (2010a): 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
2. ↑ ^{a b c} Berg, IA. et al . (2010b): Autotrophic carbon fixation in archaea . In: Nat Rev Microbiol . ; PMID 20453874 ; doi: 10.1038 / nrmicro2365
3. ↑ Thauer, RK. (2007): Microbiology. A fifth pathway of carbon fixation. In: Science 318 (5857); 1782-1783; PMID 18079388 ; doi: 10.1126 / science.1152209 .
4. ↑ Martins, BM. et al. (2004): Crystal structure of 4-hydroxybutyryl-CoA dehydratase: Radical catalysis involving a [4Fe-4S] cluster and flavin. In: PNAS 101 (44); 15645-15649; PMID 15496473 ; PDF (free full text access)

literature

• Berg, IA. et al. (2007): A 3-hydroxypropionate / 4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea . In: Science 318 (5857); 1782-1786; PMID 18079405 ; doi: 10.1126 / science.1149976