HLCS biotinylates ACACB

Stable Identifier
Reaction [transition]
Homo sapiens
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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]. 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
Catalyst Activity

biotin-protein ligase activity of HLCS [cytosol]

Orthologous Events
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