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Literature summary for 2.7.1.22 extracted from

  • Doig, C.L.; Zielinska, A.E.; Fletcher, R.S.; Oakey, L.A.; Elhassan, Y.S.; Garten, A.; Cartwright, D.; Heising, S.; Alsheri, A.; Watson, D.G.; Prehn, C.; Adamski, J.; Tennant, D.A.; Lavery, G.G.
    Induction of the nicotinamide riboside kinase NAD+ salvage pathway in a model of sarcoplasmic reticulum dysfunction (2020), Skeletal Muscle, 10, 5 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene Nmrk2, quantitative RT-PCR enzyme expression analysis Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information generation of H6PDKO/NRK2 double KO mice. H6PDKO/NRK2 double KO mice do not display an exaggerated timing or severity of myopathy or overt change in mitochondrial metabolism despite depression of NAD+ availability. Metabolome analysis Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
sarcoplasmic reticulum
-
Mus musculus 16529
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide Mus musculus
-
ADP + beta-nicotinamide D-ribonucleotide
-
?
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide Mus musculus C57/BL6J
-
ADP + beta-nicotinamide D-ribonucleotide
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus Q9D7C9
-
-
Mus musculus C57/BL6J Q9D7C9
-
-

Source Tissue

Source Tissue Comment Organism Textmining
cardiac muscle fiber
-
Mus musculus
-
skeletal muscle
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide
-
Mus musculus ADP + beta-nicotinamide D-ribonucleotide
-
?
ATP + 1-(beta-D-ribofuranosyl)-nicotinamide
-
Mus musculus C57/BL6J ADP + beta-nicotinamide D-ribonucleotide
-
?

Synonyms

Synonyms Comment Organism
nicotinamide riboside kinase
-
Mus musculus
nicotinamide riboside kinase 2
-
Mus musculus
NMRK2
-
Mus musculus
Nrk2
-
Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
Mus musculus

Expression

Organism Comment Expression
Mus musculus nicotinamide riboside kinase 2 (NRK2) expression is decreased in wild-type muscle down
Mus musculus depression of NAD+ availability leads to activation of NRK2. In cardiomyocytes, the NRK2 gene is activated by energy stress and NAD+ depletion through AMP-activated protein kinase and peroxisome proliferator-activated receptor alpha dependant mechanisms up

General Information

General Information Comment Organism
malfunction nicotinamide riboside kinase 2 (NRK2) deficiency alone has minimal impact in wild-type mice Mus musculus
malfunction induction of the nicotinamide riboside kinase NAD+ salvage pathway in a model of sarcoplasmic reticulum dysfunction. hexose-6-phosphate dehydrogenase (H6PD)-KO skeletal muscle shows adaptations in the routes regulating nicotinamide and NAD+ biosynthesis, with significant activation of the nicotinamide riboside kinase 2 (NRK2) pathway. Associated with changes in NAD+ biosynthesis, H6PD-KO muscle has impaired mitochondrial respiratory capacity with altered mitochondrial acylcarnitine and acetyl-CoA metabolism. Boosting NAD+ levels through the NRK2 pathway using the precursor nicotinamide riboside elevated NAD+/NADH but has no effect to mitigate endoplasmic reticulum stress and dysfunctional mitochondrial respiratory capacity or acetyl-CoA metabolism. Similarly, H6PD-KO/NRK2 double KO mice do not display an exaggerated timing or severity of myopathy or overt change in mitochondrial metabolism despite depression of NAD+ availability. H6PDKO/NRK2 double KO mice do not display an exaggerated timing or severity of myopathy or overt change in mitochondrial metabolism despite depression of NAD+ availability. Alterations in nicotinamide metabolism in H6PD-KO muscle, overview. Upregulation of NRK2 may be an early adaptive response to metabolic stress and the need to defend NAD+ availability Mus musculus
metabolism metabolome analysis. Upregulation of NRK2 may be an early adaptive response to metabolic stress and the need to defend NAD+ availability Mus musculus
physiological function upregulation of nicotinamide riboside kinase 2 (NRK2) mediated salvage of nicotinamide riboside into NAD+ is an early adaptation to perturbed muscle sarcoplasmic reticulum NAD(P)(H) homeostasis and impaired mitochondrial energy production in hexose-6-posphate dehydrogenase deficiency Mus musculus
physiological function NRK2 is dispensable in H6PD-KO myopathy Mus musculus