Disease relevance of USAF RH-8

• Epidemic spastic paraparesis (konzo) found in tropical and subtropical countries is known to be caused by long-term intake of cassava (Manihot esculenta Crantz), which contains a cyanoglucoside linamarin (alpha-hydroxyisobutyronitrile-beta-d-glucopyranoside) [1].

High impact information on USAF RH-8

• Mechanistic aspects of cyanogenesis from active-site mutant Ser80Ala of hydroxynitrile lyase from Manihot esculenta in complex with acetone cyanohydrin [2].
• The petiole HNL shows a simple Michaelis-Menten kinetics with Km for acetone cyanohydrin of 4.0 +/- 0.9 mM and Vmax of 46.2 +/- 5.0 micromol/min/mg [3].
• Microsomal preparations from flax seedlings have recently been shown to convert L-valine to acetone cyanohydrin, the precursor of the cyanogenic glucoside linamarin [A. J. Cutler and E. E. Conn (1981) Arch. Biochem. Biophys. 212, 468-474] [4].
• Hydroxynitrile lyase (HNL), which catalyses the conversion of acetone cyanohydrin to cyanide, is expressed predominantly in the cell walls and laticifers of leaves [5].
• The principal cyanogenic glucoside in cassava is linamarin (2-hydroxyisobutyronitrile-beta-D-glucoside) [6].

Associations of USAF RH-8 with other chemical compounds

• HNL activity against two natural substrates, acetone cyanohydrin and 2-butanone cyanohydrin, and one nonphysiological substrate, 2-pentanone cyanohydrin, was demonstrated [7].

Analytical, diagnostic and therapeutic context of USAF RH-8

• Molecular cloning of acetone cyanohydrin lyase from flax (Linum usitatissimum). Definition of a novel class of hydroxynitrile lyases [8].
• Using [1-(14)C]methacrylate (synthesized via acetone cyanhydrin), the reaction end-product was identified by peptide mapping and cocrystallization experiments as S-(2-carboxy-(2S)-propyl) substituted Cys-418 [9].

References