Homocysteine disulphides and vascular disease.
The total plasma concentration of homocysteine is a marker of this amino acid's atherogenic potential. However, the homocysteine pool exists almost entirely as oxidized homocysteine equivalents (OHcyE), composed of homocystine and cysteine-homocysteine disulphides (20-30%), and protein-bound disulphide (70-80%). We have noticed that the total concentration of OHcyE in injured coronary artery tissue is higher than the aqueous solubility of homocystine (approximately 1.4-1.5 x 10<formula>;{-3}</formula> mol kg<formula>;{-1}</formula> versus approximately 0.6 mol kg<formula>;{-1})</formula>. Based on the measurement of the solubility of homocystine in a plasma-mimetic condition (0.17 mol kg<formula>;{-1}</formula> NaCl at 37 degrees C), we have estimated that OHcyE may really reach their saturation limit in the vascular tissue (0.93-1.02 x 10<formula>{-3}</formula> mol kg<formula>;{-1})</formula>, above which their deposition as solid phase may occur. This means that significant leakage of intracellular fluid can promote OHcyE crystallization in tissue fluids, which may serve to initiate inflammation. We speculate that deposition of OHcyE crystals could damage blood vessels and act as a primer of homocysteine-triggered inflammation, thus being along the causal pathway that leads to vascular dysfunction.
Iuliano
Mauro
M
Dipartimento di Chimica, Università Federico II, Naples, Italy.
De Tommaso
Gaetano
G
Ragone
Raffaele
R
D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D006710:Homocysteine / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D009994:Osmolar Concentration; D012995:Solubility; D014652:Vascular Diseases / Q000378:metabolism*
D004220:Disulfides; D006710:Homocysteine; D003545:Cysteine