Alpha-lipoate can protect against glycation of serum albumin, but not low density lipoprotein.
Protein glycation may play a role in the pathogenesis of diabetic complications. alpha-Lipoate (1,2-dithiolane-3-pentanoate) has been reported to prevent glycation and structural modification of bovine serum albumin (BSA). To elucidate the protective mechanism, we tested the effects of enantiomerism, thiol moiety and hydrophobicity of alpha-lipoate on glycation of BSA and low density lipoprotein (LDL). When BSA (1 mM) was incubated with 500 mM glucose in the presence of alpha-lipoate homologues or dihydrolipoate (6,8-dimercaptooctanoate, DHLA) at 37 degrees C for 72 h, both alpha-lipoate (racemic, R- and S-forms) and DHLA inhibited BSA glycation similarly, but tetranorlipoate (1,2-dithiolane-3-carboxylate) did not. However, under similar conditions, alpha-lipoate did not inhibit LDL glycation. Scatchard plot analysis demonstrated that 6 mol of alpha-lipoate bind to 1 mol of BSA with a formation constant of 8.7 x 10(4) M-1. Therefore, we concluded that alpha-lipoate protects BSA glycation by hydrophobic binding near the glycation sites of BSA.
Kawabata
T
T
Department of Molecular & Cell Biology, University of California, Berkeley 94720-3200.
Packer
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L
D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D007536:Isomerism; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D008063:Thioctic Acid / Q000494:pharmacology*; D000093423:Glycated Serum Albumin; D000093844:Glycated Proteins
D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D008063:Thioctic Acid; D000093423:Glycated Serum Albumin; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins