J. Conchie

Bio: J. Conchie is an academic researcher from Rowett Research Institute. The author has contributed to research in topics: Acid hydrolysis & Aqueous solution. The author has an hindex of 13, co-authored 13 publications receiving 1039 citations.

Inhibition of glycosidases by aldonolactones of corresponding configuration. The C-4- and C-6-specificity of β-glucosidase and β-galactosidase

Abstract: 1. In barley, beta-glucosidase and beta-galactosidase are separate enzymes. The former also displays beta-d-fucosidase activity. 2. In the limpet, Patella vulgata, beta-glucosidase activity is associated with the beta-d-fucosidase, previously shown to be a separate entity from the beta-galactosidase also present. 3. Almond emulsin presents all three activities as a single enzyme. Each is equally inhibited by glucono-, galactono- and d-fucono-lactone. 4. In rat epididymis, there is no significant beta-glucosidase activity, nor is there appreciable inhibition of the beta-galactosidase and beta-d-fucosidase activities of the preparation by gluconolactone.

Inhibition of glycosidases by aldonolactones of corresponding configuration: Preparation of (1-->5)-lactones by catalytic oxidation of pyranoses and study of their inhibitory properties.

Abstract: 1. A method was devised for the preparation of (1-->5)-lactones from pyranose sugars and uronic acids by platinum-catalysed oxidation with gaseous oxygen in aqueous solution at acid pH. It was applied to mannose, N-acetylglucosamine, N-acetylgalactosamine, glucuronic acid, galacturonic acid, galactose, l-arabinose and d-fucose. 2. Only the first three yielded products that could be obtained in the solid state without decomposition. In every case, however, the oxidation product in aqueous solution behaved as the aldono-(1-->5)-lactone, and was more inhibitory towards the appropriate glycosidases than any aldonolactone preparation hitherto examined. 3. The stabilities of the oxidation products were studied, and their interconversion with the (1-->4)-lactones was demonstrated. Ring-opening does not appear to be mandatory for this isomeric change, which in some instances is very rapid. 4. To explain all the inhibitory effects observed with aldonolactones on glycosidases of corresponding configuration, it is tentatively postulated that inhibition may be due entirely to the (1-->5)-lactone, and that any inhibitory effect seen with the (1-->4)-lactone is a measure of the extent and speed of its conversion into the (1-->5)-lactone in aqueous solution.

Glycoside Hydrolases: Mechanistic Information from Studies with Reversible and Irreversible Inhibitors

Abstract: Publisher Summary This chapter discusses the results of the studies that permit some generalizations on the catalytic mechanism of glycoside hydrolases from widely differing sources and with different sugar and aglycon specificities and that have become available over the past 15 years. The strong inhibition of glycosidases by aldonolactones was first mentioned in 1940 by Japanese workers who studied β- D -glucosidases from Aspergillus (Taka-diastase) and almonds. Even though both of these groups of compounds are derived from normal substrates by only a minor modification of the glycon moiety, they are discussed together with pseudosubstrates because their reactions with glycosidases show, in many cases, unusual kinetic features. The information relevant to the mechanism of an enzyme-catalyzed reaction can, in general, only be obtained from irreversible inhibitors that react specifically at the active site, and thereby inactivate the enzyme. In many cases, inhibition studies were not carried out to obtain information on the reaction mechanism, but for other purposes. Thus, only inhibitors were tested that were considered suitable for the particular project, for example, studies on the biological function of the enzyme where glycosylamines and aldonolactones are unsuitable.

The Abnormalities of Lysosomal Enzymes in Mucopolysaccharidoses

Abstract: The activity of acid hydrolases on 13 substrates has been measured in the liver of normal human subjects and of 32 patients with various forms of mucopolysaccharidoses. The most important abnormalities may be summarized as follows: 1 In 3 patients, there was a complete absence of α-fucosidase and an excess of fucose in the mucopolysaccharide fraction. The enzymatic deficiency extended to the brain, lung, kidney and urine. In the liver there was also a large increase in the activity of several acid hydrolases, mostly of the α-galactosidase and of the β-xylosidase. 2 In 5 patients with pseudo-Hurler disease (generalized gangliosidosis), the activity of β-galactosidase, at pH 3.6 was absent and this defect also extended to other tissues. This enzymatic deficiency explains the known accumulation of galactose-rich mucopolysaccharides and of galactosyl-N-acetylgalactosaminyl N-acetyl-neuraminyl)-galactosylceramide (GM1 ganglioside) in the tissues. Several enzymatic activities were greatly elevated, mostly that of α-fucosidase, α-galactosidase and N-acetyl-β-glucosaminidase. 3 In 14 patients with an usual form of Hurler syndrome, the activity of acid β-galactosidase was markedly reduced and this abnormality extended also to the brain and the derm but not to the kidney, spleen and leucocytes. The N-acetyl-β-hexosaminidases, the β-glucuronidase and the α-fucosidase were much more active than normally. 4 In two siblings only, affected by an unusual type of Hurler syndrome, there was a marked elevation of β-galactosidase. The etiological significance of these findings is discussed and a classification of the mucopolysaccharidoses, based on the activity of the lysosomal enzymes in the liver, is proposed.