Hyperhomocysteinemia in patients with acute porphyrias: A potentially dangerous metabolic crossroad?
Acute Porphyrias
Ala-Synthase1
Homocysteine
Hyperhomocysteinemia
Vitamin B6
Journal
European journal of internal medicine
ISSN: 1879-0828
Titre abrégé: Eur J Intern Med
Pays: Netherlands
ID NLM: 9003220
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
03
09
2019
revised:
19
03
2020
accepted:
01
04
2020
pubmed:
4
6
2020
medline:
16
2
2021
entrez:
4
6
2020
Statut:
ppublish
Résumé
Acute porphyrias (AP) are characterized by heme deficiency and induction of hepatic 5-aminolevulinate synthase (ALAS1). Hyperhomocysteinemia (HHcy) is associated with endothelial damage, neurotoxicity and increased risk for vascular diseases. Interestingly, both heme biosynthesis and sulphur amino acid metabolism require vitamin B6, (Pyridoxal-phosphate, PLP) an important cofactor of ALAS1 and of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL) enzymes that catabolize homocysteine (Hcy). Moreover, heme itself is an important cofactor for CBS. to assess plasma Hcy status and HHcy main determinants in patients with AP. A total of 46 patients with AP (31 with Acute Intermittent Porphyria,15 with Variegate Porphyria) were assessed for clinical status (symptomatic vs. asymptomatic), serum Hcy, Cysteine (Cys), Vit.B6, Vit.B12, red blood cell folates and urinary delta-aminolevulinic acid (ALA) and porphobilinogen(PBG) levels (mean of six measurements). Symptomatic AP patients had significantly higher urinary ALA and PBG levels, plasma Hcy, HHcy prevalence and Hcy/Cys ratio when compared to asymptomatic carriers of AP. Even though no significant correlation was observed between ALA/PBG urinary levels and serum Hcy levels, patients with higher levels of ALA and PBG had significantly higher levels of Hcy, a higher prevalence of moderate-to severe HHcy and serum PLP levels below the 25 Most patients with symptomatic AP present HHcy resulting from alterations in sulphur amino acid metabolism. HHcy may represent an indirect marker of ALAS1 induction and its prevalence may be suggestive of a role of HHcy in the pathogenesis and/or comorbidities of AP.
Sections du résumé
BACKGROUND
Acute porphyrias (AP) are characterized by heme deficiency and induction of hepatic 5-aminolevulinate synthase (ALAS1). Hyperhomocysteinemia (HHcy) is associated with endothelial damage, neurotoxicity and increased risk for vascular diseases. Interestingly, both heme biosynthesis and sulphur amino acid metabolism require vitamin B6, (Pyridoxal-phosphate, PLP) an important cofactor of ALAS1 and of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL) enzymes that catabolize homocysteine (Hcy). Moreover, heme itself is an important cofactor for CBS.
AIM
to assess plasma Hcy status and HHcy main determinants in patients with AP.
MATERIALS AND METHODS
A total of 46 patients with AP (31 with Acute Intermittent Porphyria,15 with Variegate Porphyria) were assessed for clinical status (symptomatic vs. asymptomatic), serum Hcy, Cysteine (Cys), Vit.B6, Vit.B12, red blood cell folates and urinary delta-aminolevulinic acid (ALA) and porphobilinogen(PBG) levels (mean of six measurements).
RESULTS
Symptomatic AP patients had significantly higher urinary ALA and PBG levels, plasma Hcy, HHcy prevalence and Hcy/Cys ratio when compared to asymptomatic carriers of AP. Even though no significant correlation was observed between ALA/PBG urinary levels and serum Hcy levels, patients with higher levels of ALA and PBG had significantly higher levels of Hcy, a higher prevalence of moderate-to severe HHcy and serum PLP levels below the 25
CONCLUSIONS
Most patients with symptomatic AP present HHcy resulting from alterations in sulphur amino acid metabolism. HHcy may represent an indirect marker of ALAS1 induction and its prevalence may be suggestive of a role of HHcy in the pathogenesis and/or comorbidities of AP.
Identifiants
pubmed: 32487371
pii: S0953-6205(20)30115-1
doi: 10.1016/j.ejim.2020.04.002
pii:
doi:
Substances chimiques
Homocysteine
0LVT1QZ0BA
Cystathionine beta-Synthase
EC 4.2.1.22
Vitamin B 12
P6YC3EG204
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101-107Informations de copyright
Copyright © 2020. Published by Elsevier B.V.