The formation of H2S from
cyst(e)ine is catalyzed by three
enzymes,
cystathionine beta synthase,
cystathionase, and
3-mercaptopyruvate sulfurtransferase. In the liver, kidney, enterocytes and vascular smooth muscle cells, H2S is principally synthesized by
cystathionase. In contrast, it is synthesized by
cystathionine beta synthase in the brain and partially by
3-mercaptopyruvate sulfurtransferase in cardiac tissue. H2S is catabolized, essentially in mitochondria by
thiosulfate reductase. The
sulfite generated is then oxidized to
sulfate by
sulfite oxidase. The amount of
thiosulfate excreted in the urine is the best
indicator of H2S biosynthesis, together with
sulfhemoglobin determination in erythrocytes. H2S acts as a
neuromodulator in the brain, increasing responses mediated by
NMDA receptors, facilitating the induction of long-term potentialization in the hippocampus. H2S also acts as a
vasodilator, acting directly on
ATP-dependent
potassium channels in vascular smooth muscle cells. The concentration of H2S is abnormally low in the brains of subjects with
Alzheimer's disease, due to changes in the concentration of the physiological activator of
cystathionine beta synthase. The overproduction of H2S described in subjects with
Down's syndrome probably results from the overproduction of
cystathionine beta synthase, as the gene encoding this
protein is located on chromosome 21.