title: Nucleotide allosteric regulation of the glutamate dehydrogenases of Teladorsagia circumcincta and Haemonchus contortus.
abstract: The expression of glutamate dehydrogenase (GDH; EC 1.4.1.3) in L3 of the nematode Haemonchus contortus was confirmed by detecting GDH mRNA, contrary to earlier reports. The enzyme was active in both L3 and adult H. contortus homogenates either with NAD(+)/H or NADP(+)/H as co-factor. Although it was a dual co-factor GDH, activity was greater with NAD(+)/H than with NADP(+)/H. The rate of the aminating reaction (glutamate formation) was approximately three times higher than for the deaminating reaction (glutamate utilisation). GDH provides a pathway for ammonia assimilation, although the affinity for ammonia was low. Allosteric regulation by GTP, ATP and ADP of L3 and adult H. contortus and Teladorsagia circumcincta (Nematoda) GDH depended on the concentration of the regulators and the direction of the reaction. The effects of each nucleotide were qualitatively similar on the mammalian and parasite GDH, although the nematode enzymes were more responsive to activation by ADP and ATP and less inhibited by GTP under optimum assay condition. GTP inhibited deamination and low concentrations of ADP and ATP stimulated weakly. In the reverse direction, GTP was strongly inhibitory and ADP and ATP activated the enzyme.
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Private Bag 11-222, Palmerston North, New Zealand.
authors.forename: Saleh
authors.initials: S
authors.lastname: Umair
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Knight
authors.forename: Mark L
authors.initials: ML
authors.lastname: Patchett
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Bland
authors.forename: Heather V
authors.initials: HV
authors.lastname: Simpson
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006189:Haemonchus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007700:Kinetics; D009711:Nucleotides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D014251:Trichostrongyloidea / Q000187:drug effects / Q000201:enzymology*
chemical_list: D009711:Nucleotides; D012333:RNA, Messenger; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D005969:Glutamate Dehydrogenase