3.1Production of endogenous hydrogen sulfide
In mammalian cells, enzyme catalysis and non enzyme catalysis are two
ways to produce endogenous hydrogen sulfide. Some studies have shown
that enzyme catalysis is the main production route, and CBS, CSE and MST
are the three key enzymes of this route[22-24].
Both CBS and CSE use pyridoxal phosphate (also known as vitamin B6) as
cofactors, and their concentrations vary in different
tissues[25, 26]. CBS mainly exists in the central
nervous system (cerebellum, hippocampus) and liver
tissue[27]. CSE mainly regulates
H2S in cardiovascular system and respiratory
system[28]. These two enzymes are only present in
the cytoplasm and catalyze the conversion of homocysteine to cysteine,
generating H2S, by participating in the reverse sulfur
conversion pathway. Research has found that MST is also an enzyme
involved in endogenous H2S production[29]. Unlike
the two enzymes mentioned earlier, the cofactor of MST is zinc
(Zn)[17]. It often co catalyzes with cysteine
aminotransferase (CAT) in mitochondria to produce hydrogen sulfide,
L-cysteine, and α-Ketoglutaric acid generates 3-mercaptopyruvic acid
(3-MP) under the catalysis of CAT, and then generates hydrogen sulfide
and pyruvic acid under the action of 3-MST[30]. In
2013, a new enzyme catalysis pathway was proposed by Japanese
scientists[31]. This pathway occurs in peroxisome.
D-amino acid oxidase (DAO) catalyzes D-cysteine to produce 3-MP, and
then the product is transported to mitochondria through vesicles to
participate in the next reaction[32-34].
Endogenous hydrogen sulfide enzymatic generation pathway (as shown in
Figure 1). Some studies have found that when the human body is in the
state of oxidative stress or hyperglycemia, the hydrogen sulfide
produced through non enzyme catalysis will greatly increase. In red
blood cells, the reduction equivalent produced by glucose oxidation can
be utilized to reduce elemental sulfur or polysulfides to hydrogen
sulfide[17].
Figure 1