Figure legends
Fig.1. H2Sn can transmit signals across
cells, while S-sulfuration by MPST is restricted only inside the cells.
- H2S and H2Sn can pass
through plasma membrane of the cell in which they are produced and
reach the nearby cells as well as react with the targets inside the
produced cell. H2S S-sulfurates the S-nitrosylated
cysteine residues, while H2SnS-sulfurate the cysteine residues.
- MPST transfers sulfur from 3MP to targets inside the cell.
Fig. 2. S-sulfuration by H2Sn diffusion
and that by MPST.
- MPST produces H2Sn which reach by
diffusion to S-sulfurate H2S, cysteine, glutathione,
and cysteine residues of proteins.
- MPST sulfur transfers from 3MP to H2S, cysteine,
glutathione, and cysteine residues of proteins without being mediated
by H2Sn.
This figure is produced by modifying Kimura et al., 2017.
Fig. 3. H2S is used for ATP production at physiological
concentrations, while it inhibits cytochrome c oxidase at higher
concentrations in mitochondria. H2S is metabolized by
SQR, ETHE1, and rhodanese (TST) to thiosulfate through sulfite.
Electrons are sent to coenzyme Q to complex IV though III and used for
pumping out H+ from matrix to intermembrane space. ATP
synthase produces ATP using the gradient of H+. In
contrast, high concentrations of H2S suppress cytochrome
c oxidase and the energy formation.
Fig. 4 Diseases caused by an excess amount of H2S and
H2Sn in the central nervous system
A trisomy of choromosome 21, on which CBS is encoded, increases the
levels of CBS in Down’s syndrome. Sulfur dioxygenase, which is encoded
in ETHE1 and one of the enzymes metabolizing H2S and
H2Sn, is defective in ethylmalonyl
encephalopathy. Methylation of MPST gene increases the production of
MPST in schizophrenia. Glycolysis is decreased by the suppression of
several enzymes such as triosephosphate isomerase, phosphoglycerate
kinase, phosphopyruvate hydratase. In these diseases cytochrome c
oxidase is suppressed by high concentrations of H2S,
resulting in the decreased production of ATP.
Fig. 5. Diseases caused by a lack of H2S or
H2Sn in the central nervous system
S-sulfurated parkin in normal individuals is active, while parkin with
the same cysteine residues being S-nitrosylated in PD brains is
inactive. Mutant huntingtin suppresses the transcription of CSE gene
from SP1, resulting in the decrease in the production of
H2S. In HD animal model the activity of
cystine/glutamate antiporter xCT is suppressed and glutathione levels
are decreased, while those of ROS increased. The animal model of
Alzheimer disease shows that H2S suppresses PI3K/Akt,
while enhances the activity of STAT3. Both effects result in the
decreased production of Aβ1-42 and suppression of inflammation. In some
report the plasma levels of H2S are lower in patients of
schizophrenia than normal individuals.