biostudies-literatureUnknown58Kozich VRegulation of H<sub>2</sub>S homeostasis in humans is poorly understood. Therefore, we assessed the importance of individual enzymes in synthesis and catabolism of H<sub>2</sub>S by studying patients with respective genetic defects. We analyzed sulfur compounds (including bioavailable sulfide) in 37 untreated or insufficiently treated patients with seven ultrarare enzyme deficiencies and compared them to 63 controls. Surprisingly, we observed that patients with severe deficiency in cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) - the enzymes primarily responsible for H<sub>2</sub>S synthesis - exhibited increased and normal levels of bioavailable sulfide, respectively. However, an approximately 21-fold increase of urinary homolanthionine in CBS deficiency strongly suggests tRedox biology102517https://www.ebi.ac.uk/biostudies/studies/S-EPMC9615310biostudies-literatureHuman ultrarare genetic disorders of sulfur metabolism demonstrate redundancies in H<sub>2</sub>S homeostasis.PMC9615310Krizek TKrijt JHaack TBBarvikova KBlessing HVaculikova-Fantlova TGasperini SHonzik TStiburkova BKrizkova MNagy PSanter RClayton PSchwarz GDitroi TPorta FSchwahn BCGarcia-Cazorla AKhalil YSykut-Cegielska JJesina PSokolova JDionisi-Vici CMills PMartinelli DKuster ALaugwitz LKozich VfalseHuman ultrarare genetic disorders of sulfur metabolism demonstrate redundancies in H<sub>2</sub>S homeostasis.Regulation of H<sub>2</sub>S homeostasis in humans is poorly understood. Therefore, we assessed the importance of individual enzymes in synthesis and catabolism of H<sub>2</sub>S by studying patients with respective genetic defects. We analyzed sulfur compounds (including bioavailable sulfide) in 37 untreated or insufficiently treated patients with seven ultrarare enzyme deficiencies and compared them to 63 controls. Surprisingly, we observed that patients with severe deficiency in cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) - the enzymes primarily responsible for H<sub>2</sub>S synthesis - exhibited increased and normal levels of bioavailable sulfide, respectively. However, an approximately 21-fold increase of urinary homolanthionine in CBS deficiency strongly suggests t2022-01-01T00:00:00Z2022 Oct2025-05-31T23:30:47.219Z2024-11-12T07:53:12.38ZS-EPMC96153103630667610.1016/j.redox.2022.102517