Human ultrarare genetic disorders of sulfur metabolism demonstrate redundancies in H2S homeostasis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F22%3AN0000039" target="_blank" >RIV/00023728:_____/22:N0000039 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/22:10450644 RIV/00064165:_____/22:10450644 RIV/00216208:11310/22:10450644

Result on the web

<a href="https://doi.org/10.1016/j.redox.2022.102517" target="_blank" >https://doi.org/10.1016/j.redox.2022.102517</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.redox.2022.102517" target="_blank" >10.1016/j.redox.2022.102517</a>

Result language

angličtina

Original language name

Human ultrarare genetic disorders of sulfur metabolism demonstrate redundancies in H2S homeostasis

Original language description

Regulation of H2S homeostasis in humans is poorly understood. Therefore, we assessed the importance of in-dividual enzymes in synthesis and catabolism of H2S 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 beta-synthase (CBS) or cystathionine gamma-lyase (CSE) -the enzymes primarily responsible for H2S synthesis -exhibited increased and normal levels of bioavailable sulfide, respectively. However, an approximately 21-fold increase of urinary homolanthionine in CBS deficiency strongly suggests that lacking CBS activity is compensated for by an increase in CSE-dependent H2S synthesis from accumulating ho-mocysteine, which suggests a control of H2S homeostasis in vivo. In deficiency of sulfide:quinone oxidoreductase -the first enzyme in mitochondrial H2S oxidation -we found normal H2S concentrations in a symptomatic patient and his asymptomatic sibling, and elevated levels in an asymptomatic sibling, challenging the requirement for this enzyme in catabolizing H2S under physiological conditions. Patients with ethylmalonic encephalopathy and sulfite oxidase/molybdenum cofactor deficiencies exhibited massive accumulation of thiosulfate and sulfite with formation of large amounts of S-sulfocysteine and S-sulfohomocysteine, increased renal losses of sulfur com-pounds and concomitant strong reduction in plasma total cysteine. Our results demonstrate the value of a comprehensive assessment of sulfur compounds in severe disorders of homocysteine/cysteine metabolism and provide evidence for redundancy and compensatory mechanisms in the maintenance of H2S homeostasis.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GA19-08786S" target="_blank" >GA19-08786S: Interactions between sulfur metabolism and mitochondrial bioenergetics</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Redox Biology

ISSN

2213-2317

e-ISSN

2213-2317

Volume of the periodical

58

Issue of the periodical within the volume

Art. Nr. 102517

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

13

Pages from-to

1-13

UT code for WoS article

000878602200001

EID of the result in the Scopus database

2-s2.0-85140302226