An array of 13 biochemically well defined molecular forms of @entity291 , @entity1 and newly cloned @entity2608 ( @entity2608 ) AChEs (acetylcholinesterases) differing in glycosylation and subunit assembly status were subjected to comparative pharmacokinetic studies in @entity19 and @entity2608 . The circulatory lifetimes of recombinant @entity291 , macaque and @entity1 AChEs in @entity19 were governed by previously determined hierarchical rules; the longest circulatory residence time was obtained when @entity4360 was fully sialylated and tetramerized [Kronman, Chitlaru, Elhanany, Velan and Shafferman (2000) J. Biol. Chem. 275, 29488-29502; Chitlaru, Kronman, Velan and Shafferman (2001) Biochem. J. 354, 613-625]. In @entity2608 , @entity291 molecular forms still obeyed the same hierarchical rules, whereas primate AChEs showed significant deviation from this behaviour. Residence times of @entity1 and rhesus AChEs were effectively extended by extensive sialylation, but subunit tetramerization and N-glycan addition had a marginal effect on their circulatory longevity in macaques. It appears that the major factor responsible for the differential pharmacokinetics of @entity291 and primate AChEs in macaques is related to differences in primary structure, suggesting the existence of a specific mechanism for the circulatory clearance of primate AChEs in @entity2608 . The 35 @entity1522 that differ between @entity291 and primate AChEs are clustered within three defined domains, all located at the enzyme surface, and may therefore mediate the facilitated removal of primate cholinesterases specifically from the circulation of monkeys. These surface domains can be effectively masked by @entity968 appendage, resulting in the generation of chemically modified @entity1 and macaque AChEs that reside in the circulation for extraordinarily long periods of time (mean residence time of 10000 min). This extended residence time is similar to that displayed by native macaque butyrylcholinesterase (9950 min), which is the prevalent @entity68968 form in the circulation of adult macaques.

Amino acid domains control the circulatory residence time of primate acetylcholinesterases in @entity2608 ( XXXX ).

@entity1 :: ('9606', 'Species') :: ['human'] @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity4360 :: ('11423(Tax:10090)', 'Gene') :: ['AChE'] @entity68968 :: ('700484(Tax:9544)', 'Gene') :: ['cholinesterase'] @entity2608 :: ('9544', 'Species') :: ['rhesus macaques', 'Macaca mulatta', 'rhesus macaque'] @entity291 :: ('9913', 'Species') :: ['bovine'] @entity968 :: ('MESH:D011092', 'Chemical') :: ['poly(ethylene glycol)']
@entity2608 :: (9544,Species) :: ['Macaca mulatta']
