Reactome | GMPPB converts Mannose-1-phosphate to GDP-Mannose

GMPPB converts Mannose-1-phosphate to GDP-Mannose

Stable Identifier

R-HSA-446221

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

alpha-D-mannose 1-phosphate + GTP + H(+) => diphosphate + GDP-alpha-D-mannose

ReviewStatus

5/5

Locations in the PathwayBrowser

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Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Asparagine N-linked glycosylation (Homo sapiens)
    - Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (Homo sapiens)
      - Synthesis of substrates in N-glycan biosythesis (Homo sapiens)
        
        Synthesis of GDP-mannose (Homo sapiens)
        
        GMPPB converts Mannose-1-phosphate to GDP-Mannose (Homo sapiens)

General

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GMPPB converts Mannose-1-phosphate to GDP-Mannose

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Cytosolic mannose 1-phosphate is converted to GDP-Mannose by the mannose-1-phosphate guanyltransferase complex (GMPP). This complex consists of subunits of two closely related proteins, GMPPA and GMPPB (Verachtert H et al, 1966; Ning B and Elbein AD, 2000). Indirect evidence from patients expressing mutant forms of the proteins indicates that the guanyltransferase reaction is mediated by GMPPB while GMPPA has a regulatory function (Koehler et al. 2013). More recent structural studies of the human GMPP complex (Zheng et al. 2021) have shown that GMPPA subunits switch from a GTP-bound form (annotated here) that stimulates catalytic activity of GMPPB subunits to a GDP-mannose bound form that inhibits activity, providing a product-mediated feedback inhibition of this biosynthetic reaction.

Literature References

PubMed ID	Title	Journal	Year
24035193	Mutations in GMPPA cause a glycosylation disorder characterized by intellectual disability and autonomic dysfunction Koehler, K, Malik, M, Mahmood, S, Gießelmann, S, Beetz, C, Hennings, JC, Huebner, AK, Grahn, A, Reunert, J, Nürnberg, G, Thiele, H, Altmüller, J, Nürnberg, P, Mumtaz, R, Babovic-Vuksanovic, D, Basel-Vanagaite, L, Borck, G, Brämswig, J, Mühlenberg, R, Sarda, P, Sikiric, A, Anyane-Yeboa, K, Zeharia, A, Ahmad, A, Coubes, C, Wada, Y, Marquardt, T, Vanderschaeghe, D, Van Schaftingen, E, Kurth, I, Huebner, A, Hübner, CA	Am J Hum Genet	2013
11082198	Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase. Evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins Ning, B, Elbein, AD	Eur J Biochem	2000
5946626	Purification and properties of guanosine diphosphate hexose pyrophosphorylase from mammalian tissues Verachtert, H, Rodriguez, P, Bass, ST, Hansen, RG	J Biol Chem	1966
33986552	Cryo-EM structures of human GMPPA-GMPPB complex reveal how cells maintain GDP-mannose homeostasis Zheng, L, Liu, Z, Wang, Y, Yang, F, Wang, J, Huang, W, Qin, J, Tian, M, Cai, X, Liu, X, Mo, X, Gao, N, Jia, D	Nat Struct Mol Biol	2021