Reactome | RNR (M1M2) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin)

RNR (M1M2) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin)

Stable Identifier

R-HSA-111742

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

NDP + reduced glutaredoxin => dNDP + oxidized glutaredoxin + H2O

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

RNR (M1M2) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin)

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

Ribonucleotide reductase (RNR (M1M2)) catalyzes the reduction of adenine, guanine, cytidine, and uridine ribonucleoside 5'-diphosphates (NDPs) to form the corresponding deoxyribonucleoside 5'-diphosphates, coupled to the oxidation of glutaredoxin (Eklund et al. 2001). The enzyme complex is cytosolic (Pontarin et al. 2008). The form of ribonucleotide reductase annotated here is a tetramer of two large (M1) and two small (M2) subunits (Zhou et al. 2005). Expression of RNR (M1M2) is confined to the S phase of the cell cycle by restriction of the expression of the M2 gene and by degradation of the M2 gene product at the end of S phase (reviewed by Nordlund and Reichard 2006). The overall activity of the enzyme is regulated allosterically: ATP binding is stimulatory while dATP binding is inhibitory (Reichard et al. 2000).

The reducing equivalents needed for ribonucleotide reductase activity can be provided by either of two small proteins, glutaredoxin or thioredoxin (Holmgren 1989; Sun et al. 1998; Zahedi Avval & Holmgren 2009). Both are re-reduced with NADPH as the donor of reducing equivalents. The relative contributions of glutaredoxin and thioredoxin in vivo are unknown.

Literature References

PubMed ID	Title	Journal	Year
9677297	The NMR solution structure of human glutaredoxin in the fully reduced form Sun, C, Berardi, MJ, Bushweller, JH	J Mol Biol	1998
18997010	Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage Ferraro, P, Fijolek, A, Pontarin, G, Pizzo, P, Bianchi, V, Thelander, L, Reichard, PA, Rampazzo, C, Pozzan, T	Proc. Natl. Acad. Sci. U.S.A.	2008
19176520	Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors for Mammalian s phase ribonucleotide reductase Zahedi Avval, F, Holmgren, A	J. Biol. Chem.	2009
16756507	Ribonucleotide reductases Reichard, PA, Nordlund, P	Annu Rev Biochem	2006
2668278	Thioredoxin and glutaredoxin systems Holmgren, A	J Biol Chem	1989
10884394	Cross-talk between the allosteric effector-binding sites in mouse ribonucleotide reductase Thelander, L, Reichard, PA, Eliasson, R, Ingemarson, R	J Biol Chem	2000
11796141	Structure and function of the radical enzyme ribonucleotide reductase Farnegardh, M, Eklund, H, Nordlund, P, Logan, DT, Uhlin, U	Prog Biophys Mol Biol	2001
16373698	A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases Yen, Y, Qi, C, Yuan, YC, Su, L, Chu, B, Xi, B, Shao, J, Zhou, B, Shih, J	Mol Cancer Ther	2005