D-lysine effectively decreases the non-enzymic glycation of proteins in vitro.
Excessive non-enzymic glycation of proteins alters their physicochemical properties, with possible pathological effects. We investigated the in vitro inhibition of protein glycation by D-lysine--an isomer not incorporated into mammalian proteins but possessing the same chemical characteristics as L-lysine. Glucose incorporation was studied as follows: (a) human albumin, IgG, collagen, and isolated glomerular basement membrane were incubated for 20 days with D-glucose (5.0, 10.0, and 20.0 mmol/L) in the presence of D-lysine at 1/10 the sugar concentration; (b) albumin was incubated in similar glucose concentrations but with a constant amount (2.0 mmol/L) of D-lysine; (c) albumin and IgG were incubated for 10 days in buffer containing glucose (10 mmol/L) and increasing concentrations of D-lysine (0.25, 0.5, 1.0, 2.0, and 4.0 mmol/L); (d) inhibition specificity was tested by treating albumin as in c but with glycerol present rather than D-lysine. In addition, we measured ketoamine after incubating albumin (50 g/L) in 10 mmol/L glucose for 10 days in the presence of D-lysine (0.25, 0.5, 1.0, and 2.0 mmol/L). The results show that (a) the amount of glucose bound to the four proteins was significantly (P less than 0.05) decreased in the presence of D-lysine at the higher concentrations of glucose; (b) the lower the glucose concentration, the higher was the inhibitory effect of D-lysine; (c) the inhibition of glucose incorporation into proteins correlated directly with the concentration of D-lysine; (d) no inhibition was observed with glycerol. Ketoamine decreased with increase in D-lysine (P less than 0.01). The effective diminution of non-enzymatic glycation by D-lysine highlights its potential use in vivo.
Sensi
M
M
Department of Endocrinology, University La Sapienza, Rome, Italy.
Pricci
F
F
De Rossi
M G
MG
Morano
S
S
Di Marlo
U
U
D001485:Basement Membrane / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D019270:Fructosamine; D005947:Glucose / Q000378:metabolism*; D006031:Glycosylation; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism
D006595:Hexosamines; D007074:Immunoglobulin G; D011506:Proteins; D012709:Serum Albumin; D019270:Fructosamine; D003094:Collagen; D005947:Glucose; D008239:Lysine