Homocysteineisathiol-containingaminoacidproducedbytheintracellulardemethylationofmethionine.Homocysteineismetabolisedtoeithercysteineortomethionine.InthevitaminB6dependenttrans-sulphurationpathwayhomocysteineisirreversIBLycatabolisedtocysteine.Amajorpartofhomocysteineisremethylatedtomethionine,mainlybythefolateandcobalamindependentenzymemethioninesynthase.Homocysteineaccumulatesinthecellandisexportedtothecirculationwhenthesereactionsareimpaired1-4.Homocysteinecirculatesinplasmamostlyinitsoxidisedformboundtoproteinsandismeasuredastotalhomocysteine,(tHcy),thesumoffreeandproteinbound.SeverelyelevatedconcentrationsoftHcyarefoundinsubjectswithhomocystinuria,araregeneticdisorderoftheenzymesinvolvedinthemetabolismofhomocysteine.Patientswithhomocystinuriaexhibitmentalretardation,earlyarteriosclerosisandarterialandvenousthromboembolism.Otherlessseveregeneticdefectswhichleadtomoderatelyelevatedlevelsofhomocysteinearealsofound.Epidemiologicalresearchhasshownthatdifferentpatientgroupsmighthaveelevatedhomocysteinelevelsinblood.Morethan40epidemiologicalstudieshaveshownthatelevatedtHcyisanindependentriskfactorofcardiovasculardisease(CVD).Ametaanalysisof27ofthesestudies,includingmorethan4000patients,estimatedthata5µmol/LincreaseintHcywasassociatedwithanoddsratioof1.7forcoronaryarterydisease,1.5forcerebrovasculardiseaseorthesameincreaseinriskasfor0.5mmol/Lincreaseincholesterol9.Peripheralarterialdiseasealsoshowedastrongassociation.PatientswithchronicrenaldiseaseexperiencesanexcessmorbidityandmortalityduetoarterioscleroticCVD.ElevatedconcentrationoftHcyisafrequentobservedfindinginthebloodofthesepatients.Althoughtheymaylacksomeofthevitaminsinvolvedinthemetabolismofhomocysteine,theincreasedlevelsoftHcyaremainlyduetoimpairedremovalofhomocysteinefromthebloodbythekidney.