ArticleJournal of inherited metabolic disease2014
Reduced response of Cystathionine Beta-Synthase (CBS) to S-Adenosylmethionine (SAM): Identification and functional analysis of CBS gene mutations in Homocystinuria patients.
Article in Journal of inherited metabolic disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency.Journal of inherited metabolic disease · 2017Pooled it
- Homocystinuria: Advances in metabolic and molecular therapies targeting homocysteine pathways (Review).Molecular medicine reports · 2026Review
- Effects of Homocysteine Circulating Levels on Human Spontaneous Fertility and In Vitro Fertilization Outcomes: A Literature Review.Nutrients · 2025Review
- satmut_utils: a simulation and variant calling package for multiplexed assays of variant effect.Genome biology · 2023Article
- Cystathionine Beta-Synthase Deficiency: Three Consecutive Cases Detected in 40 Days by Newborn Screening in Emilia Romagna (Italy) and a Comprehensive Review of the Literature.Children (Basel, Switzerland) · 2023Article
- Identification of 8-Hydroxyquinoline Derivatives That Decrease Cystathionine Beta Synthase (CBS) Activity.International journal of molecular sciences · 2022Article
- Biosynthesis, Quantification and Genetic Diseases of the Smallest Signaling Thiol Metabolite: Hydrogen Sulfide.Antioxidants (Basel, Switzerland) · 2021Review
- Modulation of Human Phenylalanine Hydroxylase by 3-Hydroxyquinolin-2(1H)-One Derivatives.Biomolecules · 2021Article
- Homocysteine: Its Possible Emerging Role in At-Risk Population Groups.International journal of molecular sciences · 2020Review
- CBS mutations are good predictors for B6-responsiveness: A study based on the analysis of 35 Brazilian Classical Homocystinuria patients.Molecular genetics & genomic medicine · 2018Article
- Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology.Oxidative medicine and cellular longevity · 2018Review
- A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme CystathionineOxidative medicine and cellular longevity · 2017Article
- S-Adenosyl-l-methionine Modulates CO and NO• Binding to the Human H2S-generating Enzyme Cystathionine β-Synthase.The Journal of biological chemistry · 2016Article
- Endoplasmic Reticulum Stress and Autophagy in Homocystinuria Patients with Remethylation Defects.PloS one · 2016Article
- NO* binds human cystathionine β-synthase quickly and tightly.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A reduced response of cystathionine beta-synthase (CBS) to its allosteric activator S-adenosylmethionine (SAM) has been reported to be a cause of CBS dysfunction in homocystinuria patients. In this work we performed a retrospective analysis of fibroblast data from 62 homocystinuria patients and found that 13 of them presented a disturbed SAM activation. Their genotypic background was identified and the corresponding CBS mutant proteins were produced in E. coli. Nine distinct mutations were detected in 22 independent alleles: the novel mutations p.K269del, p.P427L, p.S500L and p.L540Q; and the previously described mutations p.P49L, p.C165Rfs*2, p.I278T, p.R336H and p.D444N. Expression levels and residual enzyme activities, determined in the soluble fraction of E. coli lysates, strongly correlated with the localization of the affected amino acid residue. C-terminal mutations lead to activities in the range of the wild-type CBS and to oligomeric forms migrating faster than tetramers, suggesting an abnormal conformation that might be responsible for the lack of SAM activation. Mutations in the catalytic core were associated with low protein expression levels, decreased enzyme activities and a higher content of high molecular mass forms. Furthermore, the absence of SAM activation found in the patients' fibroblasts was confirmed for all but one of the characterized recombinant proteins (p.P49L). Our study experimentally supports a deficient regulation of CBS by SAM as a frequently found mechanism in CBS deficiency, which should be considered not only as a valuable diagnostic tool but also as a potential target for the development of new therapeutic approaches in classical homocystinuria.
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