title: Lipid, Oxidative and Inflammatory Profile and Alterations in the Enzymes Paraoxonase and Butyrylcholinesterase in Plasma of Patients with Homocystinuria Due CBS Deficiency: The Vitamin B12 and Folic Acid Importance.
abstract: Cystathionine-β-synthase (CBS) deficiency is the main cause of homocystinuria. Homocysteine (Hcy), methionine, and other metabolites of Hcy accumulate in the body of affected patients. Despite the fact that thromboembolism represents the major cause of morbidity in CBS-deficient patients, the mechanisms of cardiovascular alterations found in homocystinuria remain unclear. In this work, we evaluated the lipid and inflammatory profile, oxidative protein damage, and the activities of the enzymes paraoxonase (PON1) and butyrylcholinesterase (BuChE) in plasma of CBS-deficient patients at diagnosis and during the treatment (protein-restricted diet supplemented with pyridoxine, folic acid, betaine, and vitamin B12). We also investigated the effect of folic acid and vitamin B12 on these parameters. We found a significant decrease in HDL cholesterol and apolipoprotein A1 (ApoA-1) levels, as well as in PON1 activity in both untreated and treated CBS-deficient patients when compared to controls. BuChE activity and IL-6 levels were significantly increased in not treated patients. Furthermore, significant positive correlations between PON1 activity and sulphydryl groups and between IL-6 levels and carbonyl content were verified. Moreover, vitamin B12 was positively correlated with PON1 and ApoA-1 levels, while folic acid was inversely correlated with total Hcy concentration, demonstrating the importance of this treatment. Our results also demonstrated that CBS-deficient patients presented important alterations in biochemical parameters, possibly caused by the metabolites of Hcy, as well as by oxidative stress, and that the adequate adherence to the treatment is essential to revert or prevent these alterations.
authors: Programa de Pós-Graduação em Ciências Biológicas:Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2700, Porto Alegre, RS, 90035-000, Brazil, cami_vanzin@hotmail.com.
authors: Camila Simioni
authors: CS
authors: Vanzin
authors: Caroline Paula
authors: CP
authors: Mescka
authors: Bruna
authors: B
authors: Donida
authors: Tatiane Grazieli
authors: TG
authors: Hammerschimidt
authors: Graziela S
authors: GS
authors: Ribas
authors: Janaína
authors: J
authors: Kolling
authors: Emilene B
authors: EB
authors: Scherer
authors: Laura
authors: L
authors: Vilarinho
authors: Célia
authors: C
authors: Nogueira
authors: Adriana Simon
authors: AS
authors: Coitinho
authors: Moacir
authors: M
authors: Wajner
authors: Angela T S
authors: AT
authors: Wyse
authors: Carmen Regla
authors: CR
authors: Vargas
mesh_terms: D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase / Q000097:blood*; D002091:Butyrylcholinesterase / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000502:physiology; D006712:Homocystinuria / Q000097:blood* / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D016877:Oxidants / Q000097:blood*; D018384:Oxidative Stress / Q000502:physiology; D014805:Vitamin B 12 / Q000097:blood / Q000502:physiology; D055815:Young Adult
chemical_list: D008055:Lipids; D016877:Oxidants; D005492:Folic Acid; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase; D003541:Cystathionine beta-Synthase; D014805:Vitamin B 12