Reactome | HLCS biotinylates ACACB

HLCS biotinylates ACACB

Stable Identifier

R-HSA-4167511

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, mitochondrial outer membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Biotin (Btn) acts as a coenzyme for 5 carboxylases that exist in their inactive apo forms. In the cytosol and mitochondrion, these apo-carboxylases are biotinylated to their active holo forms by the activity of biotin protein ligase (HCLS) (Ingaramo & Beckett 2012, Bailey et al. 2010, Hiratsuka et al. 1998). Defects in HLCS causes holocarboxylase synthetase deficiency (HLCS deficiency aka early-onset multiple carboxylase deficiency; MIM:253270). HLCS deficiency is an autosomal recessive disorder whereby deficient HLCS activity results in reduced activity of all five carboxylases. Symptoms include metabolic acidosis, organic aciduria, lethargy, hypotonia, convulsions and dermatitis (Suzuki et al. 2005). The first committed step in the synthesis of fatty acids is performed by the biotin-dependent enzyme acetyl CoA carboxylase [EC 6.4.1.2]. Acetyl CoA carboxylases 1 and 2 (ACACA and ACACB) have one Btn moiety covalently attached to each subunit (Abu-Elheiga et al. 1995). Eukaryotic acetyl-CoA carboxylases are heterodimers that can form catalytically active extended oligomers (Weatherly et al. 2004). Unlike the other biotin-dependent carboxylases that reside inside the mitochondrion, ACACA and B are located in the cytosol and outer mitochondrial membrane (shown here) respectively (Abu-Elheiga et al. 2000).

Literature References

PubMed ID	Title	Journal	Year
20153287	Holocarboxylase synthetase: correlation of protein localisation with biological function Polyak, SW, Bailey, LM, Wallace, JC	Arch. Biochem. Biophys.	2010
9630604	Identification of holocarboxylase synthetase (HCS) proteins in human placenta Suzuki, Y, Li, X, Narisawa, K, Sakamoto, O, Hiratsuka, M, Aoki, Y	Biochim. Biophys. Acta	1998
22123817	Selectivity in post-translational biotin addition to five human carboxylases Ingaramo, M, Beckett, D	J. Biol. Chem.	2012
16134170	Mutations in the holocarboxylase synthetase gene HLCS Suzuki, Y, Aoki, Y, Kure, S, Yang, X, Matsubara, Y	Hum. Mutat.	2005
14766011	Expression and characterization of recombinant fungal acetyl-CoA carboxylase and isolation of a soraphen-binding domain Weatherly, SC, Volrath, SL, Elich, TD	Biochem. J.	2004
7732023	Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms Jayakumar, A, Wakil, SJ, Chirala, SS, Baldini, A, Abu-Elheiga, L	Proc Natl Acad Sci U S A	1995
10677481	The subcellular localization of acetyl-CoA carboxylase 2 Wakil, SJ, Brinkley, WR, Woldegiorgis, G, Zhong, L	Proc Natl Acad Sci U S A	2000