Possible Interaction: Lysine and Tissue Plasminogen Activator

“… t-PA was enhanced two-fold ….4 mmol/l of lysine or 5.4 mmol/l of 6-aminohexanoic acid (6-AH) and 14–16-fold enhancement by addition of …, whereas unfractionated heparin alone gave no enhancement and in conjunction with lysine or 6-AH gave no additional enhancement.”

“The inhibitory concentrations 50% of lysine against urokinase or tissue-type plasminogen activator is 2.0 or 4.2 mM, against ε-amino-caproic acid 0.7 or 1.5 mM, against tranexamic acid 0.03 or 0.17 mM, respectively.”

“ Lysine decreased both the binding of t‐PA to PrP23‐110 and the stimulation of plasmin generation by t‐PA.”

“ Tissue plasminogen activator also interacted with antithrombin III in a time- and concentration-dependent manner and its binding was also significantly (>90%) inhibited by lysine.”

“This inhibitory action of L-lysine is largely related to the fact that it lowers the sorption of the activator, plasminogen and plasmin on fibrin, competing with fibrin for their lysine-binding sites as well as worsens the activator-plasminogen binding.”

“Moreover, excess lysine could inhibit the binding of tPA to the 45-kDa protein in both coincubation and reversibility experiments.”

“In …, type I tPA (with sugars at sites 117, 184 and 448) was found … 3-fold increased catalytic activity and an affinity for lysine which was greater than that of type I from untreated preparations, but less … control type II tPA (containing sugar only at sites 117 and 448).”

“Binding of tPA was inhibited by L-lysine , e-aminocaproic acid, and D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone but not by carbohydrates including mannose, galactose, N-acetyl glucosamine and N-acetyl galactosamine.”

“We found that occupation of the lysine binding site of tPA by a lysine or arginine side chain from the urokinase moiety is responsible for the high temperature transition as well as for the failure of the chimeras to exhibit the expected fibrin binding properties.”