Reactome | DAK dimer phosphorylates D-glyceraldehyde to form D-glyceraldehyde 3-phosphate

DAK dimer phosphorylates D-glyceraldehyde to form D-glyceraldehyde 3-phosphate

Stable Identifier

R-HSA-70349

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

ATP + D-glyceraldehyde => ADP + D-glyceraldehyde 3-phosphate + H(+), ATP + D-glyceraldehyde => ADP + D-glyceraldehyde 3-phosphate

ReviewStatus

5/5

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DAK dimer phosphorylates D-glyceraldehyde to form D-glyceraldehyde 3-phosphate

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Cytosolic dihydroxyacetone kinase (DAK) catalyzes the reaction of ATP and D-glyceraldehyde (GA) to form ADP and D-glyceraldehyde 3-phosphate (GA3P). This reaction was originally characterized in studies of guinea pig liver and human erythrocytes (Hers & Kusaka 1953; Beutler & Guinto 1973). The human enzyme has been cloned and studied (Cabezas et al. 2005; Rodrigues et al. 2014). DAK/TKFC also catalyzes the phosphorylation of dihydroxyacetone (DHA) to dihydroxyacetone phosphate (DHAP), not a necessary step in fructose catabolism, but possibly functional on exogenous DHA. Triokinase activities on GA and DHA require homodimeric enzyme formed by two-domain subunits, where triose binds to one subunit and ATP to the other, each in a different domain.
DAK/TKFC is a bifunctional enzyme which, besides the ATP/Mg-dependent phosphorylation of GA and DHA, also catalyses, in presence of Mn2+, a unisubstrate reaction splitting flavin-adenine dinucleotide (FAD) into riboflavin cyclic 4',5'-phosphate (cyclic FMN) and AMP (Cabezas et al. 2005; Rodrigues et al. 2014).
In addition, DAK/TKFC protein binds to MDA5 and acts as a negative regulator of MDA5-mediated induction of IFN-alpha/beta pathways (Diao et al. 2007). Potentially related to this TKFC effect are the observations that hepatic DAK/TKFC levels correlate with outcome in chronic hepatitis C patients treated with interferon (Perdomo et al. 2012), and that a DAK/TKFC serum peptide is a predictor of disease severity in hepatitis B patients (Xu et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
16289032	Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-dependent dihydroxyacetone kinases Cabezas, A, Costas, MJ, Pinto, RM, Couto, A, Cameselle, JC	Biochem. Biophys. Res. Commun.	2005
13093749	[The metabolism of fructose-1-phosphate in the liver.] Hers, HG, Kusaka, T	Biochim Biophys Acta	1953
24289155	Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B Xu, MY, Jia, XF, Qu, Y, Zheng, RD, Yuan, ZH, Weng, HL, Dooley, S, Wang, XP, Zhang, LJ, Lu, LG	J Transl Med	2013
22098443	Liver protein profiling in chronic hepatitis C: identification of potential predictive markers for interferon therapy outcome Perdomo, AB, Ciccosanti, F, Iacono, OL, Angeletti, C, Corazzari, M, Daniele, N, Testa, A, Pisa, R, Ippolito, G, Antonucci, G, Fimia, GM, Piacentini, M	J. Proteome Res.	2012
4688871	Dihydroxyacetone metabolism by human erythrocytes: demonstration of triokinase activity and its characterization Beutler, E, Guinto, E	Blood	1973
24569995	Bifunctional homodimeric triokinase/FMN cyclase: contribution of protein domains to the activities of the human enzyme and molecular dynamics simulation of domain movements Rodrigues, JR, Couto, A, Cabezas, A, Pinto, RM, Ribeiro, JM, Canales, J, Costas, MJ, Cameselle, JC	J. Biol. Chem.	2014