Acetyl-CoA carboxylase

Acetyl-CoA carboxylase
Mass / length primary structure	2346 amino acids
Secondary to quaternary structure	Dimer, tetramer, oligomer
Cofactor	Biotin , Mn 2+
Isoforms	4th
Identifier
Gene name (s)	ACACA , ACACB
External IDs	OMIM :  200350 UniProt :  Q13085
Enzyme Classifications
EC, category	6.4.1.2 ,  ligase
Response type	addition
Substrate	ATP + acetyl-CoA + HCO 3 - + H +
Products	ADP + malonyl-CoA + phosphate + H 2 O
EC, category	6.3.4.14 ,  carboxylase
Response type	Carboxylation
Substrate	ATP + protein-biotin + HCO 3 - + H +
Products	ADP + protein-carboxybiotin + phosphate + H 2 O
Occurrence
Parent taxon	Creature

The acetyl-CoA carboxylase (ACC) is the enzyme which has the chemical addition of carbon dioxide to acetyl-CoA catalyzed wherein malonyl-CoA is produced. This reaction is the first and rate-determining step in the fatty acid synthesis of all living things. In detail, the reaction takes place in two steps, which are only catalyzed by one and the same enzyme in eukaryotes and some bacteria ; with all others two enzymes are necessary for this. Humans have two isozymes, ACC1 ( cytosolic ) and ACC2 ( mitochondrial ), which are encoded by the ACACA and ACACB genes . Mutations in the ACACA gene can lead to enzyme defects and these lead to the rare hereditary disease ACC deficiency with severe brain damage and muscle weakness.

According to a study, polymorphisms in the ACACB gene could be responsible for metabolic syndrome . In addition to its regulation by transcription factors (SREBP1) or phosphorylation by AMPK , ACC activity is controlled by the degree of enzyme polymerization, which is influenced by the protein MIG12.

Catalyzed reaction

Reaction mechanism of the ACC1 / 2

The overall reaction that takes place is:

${\displaystyle \mathrm {ATP+Acetyl{\text{-}}CoA+HCO_{3}^{-}+{\text{2 }}H_{2}O\longrightarrow ADP+Malonyl{\text{-}}CoA+{\text{2 }}H_{3}O^{+}+P_{i}} }$

In detail there are two reactions in succession:

${\displaystyle \mathrm {ATP+HCO_{3}^{-}+Protein{\text{-}}Biotin+{\text{2 }}H_{2}O\longrightarrow ADP+Protein{\text{-}}Biotin{\text{-}}COO^{-}+{\text{2 }}H_{3}O^{+}+P_{i}} }$

First, carbonate is added to the biotin residue, which consumes one molecule of ATP.

${\displaystyle \mathrm {Protein{\text{-}}Biotin{\text{-}}COO^{-}+Acetyl{\text{-}}CoA\rightleftharpoons Protein{\text{-}}Biotin+Malonyl{\text{-}}CoA} }$

Then carbonate is transferred to acetyl CoA. In animals, both reactions take place on the same enzyme, which both carries the two necessary catalytic domains and serves as a biotin carrier protein. In all other organisms these binding sites are found on several individual proteins, which in turn form a protein complex .

literature

• PN Black, CC DiRusso: Yeast acyl-CoA synthetases at the crossroads of fatty acid metabolism and regulation. In: Biochimica et biophysica acta Volume 1771, Number 3, March 2007, pp. 286-298. doi : 10.1016 / j.bbalip.2006.05.003 . PMID 16798075 . (Review).

Individual evidence

1. ↑ UniProt O13085 , UniProt O00763
2. ↑ ^{a b} G. Gago, D. Kurth u. a .: Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. In: Journal of bacteriology Volume 188, Number 2, January 2006, pp. 477-486. doi : 10.1128 / JB.188.2.477-486.2006 . PMID 16385038 . PMC 134727 (free full text).
3. ↑ CM Phillips, L. Goumidi et al. a .: ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat. In: Journal of lipid research Volume 51, Number 12, December 2010, pp. 3500-3507. doi : 10.1194 / jlr.M008474 . PMID 20855566 . PMC 297572 (free full text).
4. ↑ CW Kim, YA Moon et al. a .: Induced polymerization of mammalian acetyl-CoA carboxylase by MIG12 provides a tertiary level of regulation of fatty acid synthesis. In: Proceedings of the National Academy of Sciences of the United States of America Volume 107, Number 21, May 2010, pp. 9626-9631. doi : 10.1073 / pnas.1001292107 . PMID 20457939 . PMC 290688 (free full text).

Web links

Wikibooks: Saturated Fatty Acids Biosynthesis  - Learning and Teaching Materials

• Gopinathrao G: Transcriptional activation of acetyl-CoA carboxylase by ChREBP: MLX. In: reactome.org. EBI, 2007, accessed September 1, 2011 . 
• Gopinathrao G: Formation of Malonyl-CoA from Acetyl-CoA (muscle). In: reactome.org. EBI, 2007, accessed September 1, 2011 . 
• Gopinathrao G: pAMPK inactivates ACC2 inhibiting malonyl-CoA synthesis. In: reactome.org. EBI, 2007, accessed September 1, 2011 .