Disease relevance of NAGK

• The activities of hexokinase III and N-acetylglucosamine kinase were unchanged in cirrhosis [1].
• The activities of hexokinase isoenzymes I-IV (EC 2.7.1.1) and of N-acetylglucosamine kinase (EC 2.7.1.59) were determined in normal human liver and in alcoholic liver disease and primary biliary cirrhosis after FPLC fractionation of high-speed supernatants on Mono-Q with a linear NaCl gradient [1].
• Screening of Synechococcus sp. strain PCC 7942 libraries with PII as bait resulted in identification of N-acetyl glutamate kinase (NAGK), a key enzyme in the biosynthesis of arginine [2].
• In cyanobacteria, NAGK is a key enzyme in arginine biosynthesis [3].

High impact information on NAGK

• Structural comparison of StHK with human N-acetylglucosamine kinase and other hexokinases provides an explanation for the ability of StHK to phosphorylate both glucose and N-acetylglucosamine [4].
• N-Acetyl-L-glutamate kinase (NAGK), the structural paradigm of the enzymes of the amino acid kinase family, catalyzes the phosphorylation of the gamma-COO(-) group of N-acetyl-L-glutamate (NAG) by ATP [5].
• The active site is too narrow to accommodate the substrates without compressing the reacting groups, and this compressive strain appears a crucial component of the catalytic mechanism of NAGK, and possibly of other enzymes of the amino acid kinase family such as carbamate kinase [5].
• The integrity of Ser49, a residue conserved in PII proteins from organisms that perform oxygenic photosynthesis, appears to be essential for NAGK binding [2].
• Murine N-acetylglucosamine kinase contains six cysteine residues, all of which were mutated to serine residues [6].

Biological context of NAGK

• Previous biochemical studies have indicated that allosteric regulation of the first and, especially, the second steps in Orn synthesis (NAGS; N-acetylglutamate kinase (NAGK), EC 2.7.2.8) by the Arg end-product are the major sites of metabolic control of the pathway in organisms using the cyclic pathway [7].
• In Daucus carota, N-acetylglutamate-5-phosphotransferase (NAGK; E.C. 2.7.2.8) specific activity was shown to correlate with the progression of somatic embryogenesis and was highest in the latter stages, where growth was most rapid [8].
• Gene expression profiling for pathway enzymes further suggests that NAGS, NAGK, NAOGAcT and NAOD are coordinately regulated in response to changes in Arg demand during plant growth and development [7].

Anatomical context of NAGK

• N-acetylglucosamine kinase and N-acetylglucosamine 6-phosphate deacetylase in normal human erythrocytes and Plasmodium falciparum [9].
• A dextrose salt mixture (GNK) was found to enhance intracellular uptake of 51Cr significantly (8-fold) without affecting viability of the cells or without causing selective loss of lymphocyte subpopulations [10].

Associations of NAGK with chemical compounds

• During the search for inhibitors of N-acetylneuraminic acid biosynthesis, it was shown that 3-O-methyl-N-acetylglucosamine competitively inhibits the N-acetylglucosamine kinase of rat liver in vitro with a Ki value of 17 microM [11].
• CaNag5p recognized glucose and mannose as substrates, whereas the recently identified human GlcNAc kinase was specific to GlcNAc [12].
• A gel filtration analysis of BJA-B K88 control cells, which express UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, revealed two N-acetylmannosamine kinase activity peaks, one co-eluting with UDP-N-acetylglucosamine 2-epimerase activity and one co-eluting with N-acetylglucosamine kinase [13].
• Interestingly, the nag5 strain which lacks an N-acetylglucosamine kinase showed enhanced filamentation and invasive growth as well as increased resistance against farnesol [14].

References