Background: Oxidative stress is a complicating factor in chronic renal failure, especially in hemodialysis (HD) patients. Also, aluminum intoxication may occur during hemodialysis treatment. Aluminum has been shown to inhibit the sulfhydryl-containing enzyme delta-aminolevulinate dehydratase (ALA-D). Thus, the involvement of -SH oxidation in ALA-D inhibition and its relationship with serum Al levels and lipid peroxidation in HD patients were evaluated.
Methods: Blood ALA-D activity, plasma thiobarbituric acid reactive substances (TBARS), and serum aluminum levels were measured in HD patients (n=37) and healthy controls (n=20).
Results: TBARS and Al levels were higher in HD patients than in controls (p<0.01), while ALA-D activity was lower (p<0.05). The sulfhydryl-reducing agent dithiothreitol (DTT) reactivated ALA-D of HD patients, but activity was still lower than that of controls. ALA-D activity was negatively correlated with TBARS (r=-0.63, p<0.01) and aluminum levels (r=-0.31, p<0.05).
Conclusions: Reduced ALA-D activity in HD patients was found to be related to the oxidation of -SH groups essential for enzyme activity. Our results suggest that increased oxidative stress may have contributed to enzyme inhibition in HD patients.
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http://dx.doi.org/10.1016/j.clinbiochem.2007.02.007 | DOI Listing |
Hematology Am Soc Hematol Educ Program
December 2024
Harvard Medical School, Boston, MA.
The acute hepatic porphyrias (AHPs) are a family of rare genetic diseases associated with attacks of abdominal pain, vomiting, weakness, neuropathy, and other neurovisceral symptoms. Pathogenic variants in 1 of 4 enzymes of heme synthesis are necessary for the development of AHP, and the onset of acute attacks also requires the induction of δ-aminolevulinic acid synthase 1 (ALAS1), the first and rate-limiting step of heme synthesis in the liver. Givosiran is an RNA interference medication that inhibits hepatic ALAS1 and was designed to treat AHP.
View Article and Find Full Text PDFJ Clin Med
November 2024
Porphyria Center, Chemnitz Hospital, 09116 Chemnitz, Germany.
: Acute intermittent porphyria (AIP) is a metabolic disease characterised by neurovisceral crises with episodes of acute abdominal pain alongside life-altering, and often hidden, chronic symptoms. The elimination of precipitating factors, hemin therapy, and pain relief are strategies used to treat porphyria symptoms, but are often reserved for patients suffering recurrent, acute attacks. Givosiran (siRNA) is an emerging AIP therapy capable of silencing delta-aminolevulinic acid synthase-1 (ALAS1) and, in turn, reducing the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) that precede porphyria symptoms.
View Article and Find Full Text PDFPrep Biochem Biotechnol
November 2024
College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, People's Republic of China.
5-aminolevulinic acid (ALA) is a non-protein amino acid that has been widely used in the fields of medicine and agriculture. This study aims to engineer the C5 pathway of the ALA biosynthesis in BL21 to enhance ALA production. The ALA synthase genes , and were overexpressed in BL21 to lead to the increase in the production of ALA.
View Article and Find Full Text PDFDig Dis Sci
November 2024
University of Texas Medical Branch, Galveston, TX, USA.
Rev Clin Esp (Barc)
December 2024
Unidad de Enfermedades Raras y Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
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