Hydrogen sulfide reactions

[z-haiman]

Brief description:

All reactions should depend on one form of H2S/HS(-) and have the deprotonation reaction. Issue can be resolved by removing all of the H2S versions and keep all of the HS(-) versions.

Reasons for HS- over H2S:

From Wang R. Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol Rev. 2012 Apr;92(2):791-896. doi: 10.1152/physrev.00017.2011. PMID: 22535897.

The definition of what constitutes free sulfide, as opposed to bound sulfide, should also be noted. Free sulfide is dissolved H2S gas, which is a weak acid and in solution exists in the equilibrium H2S ↔ HS− ↔ S2−. With the pKa1 ∼7.0 and the pKa2 >17, there is essentially no S2− in biological tissues, nearly equal amounts of H2S and HS− within the cell, and approximately a 20% H2S/80% HS− ratio in extracellular fluid and plasma at 37°C and pH 7.4. Due to the temperature sensitivity of pKa1, the H2S/HS− ratio remains nearly constant in blood and tissues of ectothermic vertebrates over a wide range of body temperatures. For example, in trout blood at 10°C, the ratio is 15% H2S/85% HS−.

From Jennings ML. Transport of H2S and HS(-) across the human red blood cell membrane: rapid H2S diffusion and AE1-mediated Cl(-)/HS(-) exchange. Am J Physiol Cell Physiol. 2013 Nov 1;305(9):C941-50. doi: 10.1152/ajpcell.00178.2013. Epub 2013 Jul 17. PMID: 23864610; PMCID: PMC4042536.

The data indicate that HS(-) is a very good substrate for AE1; the Cl(-)/HS(-) exchange rate is about one-third as rapid as Cl(-)/HCO3(-) exchange. The H2S permeability coefficient must also be high (>10(-2) cm/s, half time <0.003 s) to account for the pH equilibration data.

Most physiological scenarios for RBCs will have HS- prevalent over H2S due to the pH, and Band 3 can exchange HS(-).

Current status:

Identifier	Reaction equation	Genes
H2SMT	amet__L_c + h2s_c --> ahcys__L_c + ch4s_c + h_c	TMT1A
HTSULDHLA	dhlipoate_c + htsul_c --> h2s_c + h_c + lipoate_c + so3_c	MPST
MTOX	ch4s_c + h2o_c + o2_c --> fald_c + h2o2_c + h2s_c	SELENBP1
SPODM2	h2s_c + 2.0 o2_c --> 2.0 h_c + so4_c	SOD1

Proposed status/to-do list:

Identifier	Reaction equation	Genes
H2SMT	amet__L_c + sh1_c --> ahcys__L_c + ch4s_c	TMT1A
HTSULDHLA	dhlipoate_c + htsul_c --> sh1_c + 2 h_c + lipoate_c + so3_c	MPST
MTOX	ch4s_c + h2o_c + o2_c --> fald_c + h2o2_c + sh1_c + h_c	SELENBP1
SPODM2	sh1_c + 2.0 o2_c --> h_c + so4_c	SOD1

• Update stoichiometry for H2SMT.
• Update stoichiometry for HTSULDHLA.
• Update stoichiometry for MTOX.
• Update stoichiometry for SPODM2.