Nutritional essentiality of sulfur in health and disease

Ingenbleek, Yves; Kimura, Hideo

doi:10.1111/nure.12050

Cited by 99 publications

(78 citation statements)

References 275 publications

(576 reference statements)

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“…This is equivalent to between 1 and 56 mmol ROS per day; at an average of 0.1% ROS/mol O 2 , this is 16 mmol/day. The average intake of sulfur amino acids (S-AA) is 26 mmol/day, and S-AA from protein turnover adds another 70 mmol/day, ϳ90% (88 mmol/day) of which is used for protein synthesis (19,20). Of the remaining 10 mmol, approximately half are desulfurated (59), generating 5 mmol H 2 S/day.…”

Section: Discussionmentioning

confidence: 99%

A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

DeLeon

Gao

Huang

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Stepwise one-electron reduction of oxygen to water produces reactive oxygen species (ROS) that are chemically and biochemically similar to reactive sulfide species (RSS) derived from one-electron oxidations of hydrogen sulfide to elemental sulfur. Both ROS and RSS are endogenously generated and signal via protein thiols. Given the similarities between ROS and RSS, we wondered whether extant methods for measuring the former would also detect the latter. Here, we compared ROS to RSS sensitivity of five common ROS methods: redox-sensitive green fluorescent protein (roGFP), 2', 7'-dihydrodichlorofluorescein, MitoSox Red, Amplex Red, and amperometric electrodes. All methods detected RSS and were as, or more, sensitive to RSS than to ROS. roGFP, arguably the "gold standard" for ROS measurement, was more than 200-fold more sensitive to the mixed polysulfide H2Sn(n = 1-8) than to H2O2 These findings suggest that RSS may be far more prevalent in intracellular signaling than previously appreciated and that the contribution of ROS may be overestimated. This conclusion is further supported by the observation that estimated daily sulfur metabolism and ROS production are approximately equal and the fact that both RSS and antioxidant mechanisms have been present since the origin of life, nearly 4 billion years ago, long before the rise in environmental oxygen 600 million years ago. Although ROS are assumed to be the most biologically relevant oxidants, our results question this paradigm. We also anticipate our findings will direct attention toward development of novel and clinically relevant anti-(RSS)-oxidants.

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Section: Discussionmentioning

confidence: 99%

A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

DeLeon

Gao

Huang

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Third, arguments can be made against H 2 S inhibition of O 2 consumption based on mass balance of sulfur and O 2 metabolism. A 70 kg adult male ingests *26 mmol of sulfur amino acids per day, and total sulfur intake is probably *40 mmol per day (62,118). O 2 consumption is *250 ml/ min (179), or 360 L/day, which is equivalent to 15 mol of O 2 per day.…”

Section: H 2 S and O 2 Sensingmentioning

confidence: 99%

Hydrogen sulfide as an oxygen sensor

Olson

2013

Clinical Chemistry and Laboratory Medicine

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Significance: Although oxygen (O 2 )-sensing cells and tissues have been known for decades, the identity of the O 2 -sensing mechanism has remained elusive. Evidence is accumulating that O 2 -dependent metabolism of hydrogen sulfide (H 2 S) is this enigmatic O 2 sensor. Recent Advances: The elucidation of biochemical pathways involved in H 2 S synthesis and metabolism have shown that reciprocal H 2 S/O 2 interactions have been inexorably linked throughout eukaryotic evolution; there are multiple foci by which O 2 controls H 2 S inactivation, and the effects of H 2 S on downstream signaling events are consistent with those activated by hypoxia. H 2 S-mediated O 2 sensing has been demonstrated in a variety of O 2 -sensing tissues in vertebrate cardiovascular and respiratory systems, including smooth muscle in systemic and respiratory blood vessels and airways, carotid body, adrenal medulla, and other peripheral as well as central chemoreceptors. Critical Issues: Information is now needed on the intracellular location and stoichometry of these signaling processes and how and which downstream effectors are activated by H 2 S and its metabolites. Future Directions: Development of specific inhibitors of H 2 S metabolism and effector activation as well as cellular organelle-targeted compounds that release H 2 S in a timeor environmentally controlled way will not only enhance our understanding of this signaling process but also provide direction for future therapeutic applications. Antioxid. Redox Signal. 22, 377-397.

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“…Methionine is one of eight essential amino acids required for the synthesis of body proteins as well as a number of crucial functions, including the ribosomal initiation of protein synthesis, and is a modulator of metabolic flux and catalytic activities (Ingenbleek and Kimura 2013). The finding that treatment with B12 both improves clinical symptoms and is more likely to produce a clinical response in patients with a low baseline level of methionine adds strength to these findings, and suggests that methyl B12 may be a valuable treatment for a defined subset of children with ASD.…”

Section: Methyl B12 For Autismmentioning

confidence: 99%

Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism

Widjaja

et al. 2016

Journal of Child and Adolescent Psychopharmacology

106

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Objective: Children with autism spectrum disorder (ASD) have been reported to have reduced ability to methylate DNA and elevated markers of oxidative stress. We sought to determine if methyl B12, a key metabolic cofactor for cellular methylation reactions and antioxidant defense, could improve symptoms of ASD. Methods: A total of 57 children with ASD were randomly assigned to 8 weeks of treatment with methyl B12 (75 lg/kg) or saline placebo every 3 days in a subcutaneous injection. The primary outcome measure was overall improvement in symptoms of ASD as measured by the Clinical Global Impressions-Improvement (CGI-I) score. Secondary outcome measures included changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Laboratory measures of methionine methylation and antioxidant glutathione metabolism were assessed at baseline and 8 weeks.Results: A total of 50 children (mean age 5.3 years, 79% male) completed the study. The primary outcome measure -the clinician rated CGI-I score -was statistically significantly better (lower) in the methyl B12 group (2.4) than in the placebo group (3.1) (0.7 greater improvement in the methyl B12 group, 95% CI 1.2-0.2, p = 0.005). Clinical improvement among children treated with methyl B12 was positively correlated with increases in plasma methionine ( p = 0.05), decreases in S-adenosyl-lhomocysteine (SAH) ( p = 0.007) and improvements in the ratio of S-adenosylmethionine (SAM) to SAH ( p = 0.007), indicating an improvement in cellular methylation capacity. No improvements were observed in the parent-rated ABC or SRS. Conclusions: Methyl B12 treatment improved clinician-rated symptoms of ASD that were correlated with improvements in measures of methionine metabolism and cellular methylation capacity. Clinical Trial Registry: Efficacy Study of Subcutaneous Methyl B12 in Children with Autism: NCT01039792 (clinical trials.gov1).

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Nutritional essentiality of sulfur in health and disease

Cited by 99 publications

References 275 publications

A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

Hydrogen sulfide as an oxygen sensor

Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism

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