Homocysteinuria was manifested by the cardiovascular, ophthalmologic and systemic symptoms in which the luxation and subluxation of lens were reasons for consultation. The biochemical cause was the cystathionin synthetase deficiency leading the metabolic disorder of methionin. The treatment involved the long-term use of high dose of vitamin B6 and reduction of the food that containing much methionin. It should not operate in the anesthetic condition. The current technique is cystitomy
Cardiovascular Diseases ; Cystathionine beta-Synthase

Classical hemocystinuria is an inborn error of metabolism caused by a deficiency of cystathionine beta-synthase that converts hemocysteine to cystathionine. This then leads to elevation of hemocysteine which results in abnormalities of the eyes, skeleton, central nervous system and vascular hemocystinuria. Patient 1 presented with lens dislocation and mental retardation while Patient 2 presented with thromboembolism, mental retardation and lens dislocation. The elevated plasma hemocysteine and methionine levels lead to the diagnosis of hemocystinuria.
Human ; Male ; Child ; CYSTATHIONINE ; CYSTATHIONINE BETA-SYNTHASE ; INTELLECTUAL DISABILITY

Hydrogen sulfide (H2S) is the third type of active endogenous gaseous signal molecule following nitric oxide (NO) and carbon monoxide (CO). In mammalians, H2S is mainly synthesized by two proteases, cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). H2S plays an essential function of physiological regulation in vivo, and promotes penile erection by acting on the ATP-sensitive potassium channels to relax the vascular smooth muscle as well as by the synergistic effect with testosterone and NO to relax the corpus cavernosum smooth muscle (CCSM). At present, the selective phosphodiesterase type 5 (PDE5) inhibitor is mainly used for the treatment of erectile dysfunction (ED), but some ED patients fail to respond. Therefore, further studies on the mechanism of H2S regulating penile erection may provide a new way for the management of erectile dysfunction.
Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Humans ; Hydrogen Sulfide ; Male ; Penile Erection

The purpose of the present study is to investigate the effect of L-cysteine on colonic motility and the underlying mechanism. Immunohistochemical staining and Western blot were used to detect the localization of the HS-generating enzymes cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). Organ bath system was used to observe the muscle contractile activities. Whole-cell patch-clamp technique was applied to record ionic channels currents in colonic smooth muscle cells. The results showed that both CBS and CSE were localized in mucosa, longitudinal and circular muscle and enteric neurons. L-cysteine had a dual effect on colonic contraction, and the excitatory effect was blocked by pretreatment with CBS inhibitor aminooxyacetate acid (AOAA) and CSE inhibitor propargylglycine (PAG); L-cysteine concentration-dependently inhibited L-type calcium channel current (I) without changing the characteristic of L-type calcium channel (P < 0.01); In contrast, the exogenous HS donor NaHS increased I at concentration of 100 μmol/L, but inhibited I and modified the channel characteristics at concentration of 300 μmol/L (P < 0.05); Furthermore, L-cysteine had no effect on large conductance calcium channel current (I), but NaHS significantly inhibited I (P < 0.05). These results suggest that L-cysteine has a potential dual effect on colonic smooth muscle and the inhibitory effect might be directly mediated by L-type calcium channel while the excitatory effect might be mediated by endogenous HS.
Cystathionine beta-Synthase ; Cystathionine gamma-Lyase ; Cysteine ; pharmacology ; Hydrogen Sulfide ; Muscle, Smooth

OBJECTIVETo investigate the expressions of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) in the corpus cavernosum of spontaneous hypertensive rats (SHR) and their relationship with erectile dysfunction.

METHODSThis study included 10 male SHRs and 10 healthy male Wistar-Kyoto (WKY) rats as controls, all aged 12 weeks. We applied a series of electric stimuli to the major pelvic ganglions of the rats, observed changes in the ratio of intracavernosal to mean arterial blood pressure (ICP/MAP), measured the levels of serum testosterone (T) and endogenous H2S, and determined the expressions of CSE and CBS in the corpus cavernosum by Western blot and immunohistochemistry.

RESULTSNo obvious difference was found in the serum T level between the two groups. Compared with the WKY rats, the SHRs showed significant reduction in the ICP/MAP ratio, the contents of plasma H2S ([21.92 +/- 2.75] micromol/L vs [10.49 +/- 1.35] micromol/L, P < 0.05) and endogenous corpus cavernosal H2S ([87.67 +/- 2.12] nmol/mg prot vs [52.60 +/- 3.44] nmol/mg prot, P < 0.05), the level of endogenous H2S synthesis ([4.35 +/- 0.32] nmol/mg per min vs [1.14 +/- 0.07] nmol/mg per min, P < 0.05) and the expressions of CBS and CSE (P < 0.05). Immunohistochemistry showed that CSE and CBS were distributed mainly in the smooth muscle cells and vascular endothelial cells of the corpus cavernosum. The ICP/MAP ratio was highly positively correlated with the expressions of CSE (r = 0.977, P < 0.05) and CBS (r = 0.955, P < 0.05) in the corpus cavernosal tissue.

CONCLUSIONHypertension inhibits endogenous H2S synthesis by suppressing the expressions of CSE and CBS in the corpus cavernosum, which might be related with hypertension-induced reduction of erectile function.

Animals ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Gene Expression Regulation ; Hydrogen Sulfide ; blood ; Hypertension ; metabolism ; Male ; Penis ; enzymology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

OBJECTIVETo investigate the role of endogenous hydrogen sulfide (H2S) in erectile dysfunction (ED) induced by androgen deficiency.

METHODSWe randomly divided 30 eight-week-old healthy male SD rats into six groups: 2-week control (A), 4-week control (B), 2-week castration (C), 4-week castration (D), 2-week castration + androgen replacement (E), and 4-week castration + androgen replacement (F), those in groups E and F subcutaneously injected with testosterone propionate (TP) at the physiological dose of 3 mg/kg per day after castration, while those in the other groups with isodose oil instead. At 2 and 4 weeks after operation, we determined the level of serum testosterone (T) , intracavernous pressure (ICP) , mean carotid arterial pressure (MAP) of the rats, measured the concentration of H2S in the plasma and corpus cavernosum tissue, and detected the expressions of cystathionine-P3-synthase (CBS) and cystathionine-gamma-lyase (CSE) by immunohistochemistry and Western blot.

RESULTSThe serum T level was significantly lower in group C ([0.63 +/- 0.15] nmol/L) than in A ( [ 16.55 +/- 4.17] nmol/L) and E ( [ 18.99 +/- 4.62] nmol/L) (P <0.05), as well as in group D ([0.70 +/-0.22] nmol/L) than in B ([15.44 +/-5.18] nmol/L) and F ([20.99 +/-6.41] nmol/L) (P <0. 05) , and so were ICP/MAP after 5 and 7 V electrical stimulation of the pelvic ganglia (P <0. 05) , H2 S concentration (P <0.05), and the expressions of CBS and CSE (P <0.05). The expressions of CBS and CSE proteins were also significantly decreased in group C as compared with D (P <0.05).

CONCLUSIONThe reduced expressions of CBS and CSE may inhibit the H2 S signaling pathway, which might be one of the mechanisms underlying androgen deficiency-induced ED in rats.

Androgens ; deficiency ; Animals ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Erectile Dysfunction ; metabolism ; Hydrogen Sulfide ; metabolism ; Male ; Orchiectomy ; Penis ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the expressions of cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) in the corpus cavernosum smooth muscle of castrated rats and their roles in erectile dysfunction after castration.

METHODSWe randomly assigned 40 eight-week-old male SD rats to groups A (2-week sham-operation), B (4-week sham-operation), C (2-week castration) and D (4-week castration). We determined the level of serum testosterone (T) and the expressions of CBS and CSE in the corpus cavernosum smooth muscle of the rats after operation using immunohistochemistry and RT-PCR.

RESULTSThe T level was significantly decreased in groups C ([11.85 +/- 6.73] nmol/L) and D ([1.96 +/- 1.23] nmol/L) as compared with A ([89.65 +/- 17.13] nmol/L) and B ([106.75 +/- 19.68] nmol/L) (P < 0.05). CBS and CSE were expressed in all groups of rats, but the relative expressions of CBS and CSE mRNA were significantly lower in groups C (0.93 +/- 0.14 and 0.87 +/- 0.20) and D (0.79 +/- 0.17 and 0.71 +/- 0.12) than in A (2.13 +/- 0.65 and 1.93 +/- 0.15) and B (2.07 +/- 0.53 and 1.89 +/- 0.45) (P < 0. 05), so were the optical density values (IA) of the CBS and CSE proteins, 130.35 +/- 23.56 and 93.56 +/- 36.64 in group C and 80.29 +/- 29.65 and 58.56 +/- 19.95 in group D, as compared with 310.57 +/- 130.56 and 269.56 +/- 116.76 in group A and 349.68 +/-112.35 and 298.35 +/- 100.76 in group B (P < 0.05). The androgen level was positively correlated with the expressions of CBS and CSE in the corpus cavernosum smooth muscle of the rats.

CONCLUSIONAndrogen regulates erectile function via the expressions of CBS and CSE.

Animals ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Male ; Muscle, Smooth ; enzymology ; Orchiectomy ; Penis ; enzymology ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood

Arteriosclerosis and its complications, such as heart attack and stroke, are the major causes of death in developed countries. It was believed that age, hyperlipidemia, hypertension, diabetes and smoking are common risk factors for cardiovascular disease. In addition, overwhelming clinical and epidemiological studies have identified homocysteine (Hcy) as a significant and independent risk factor for cardiovascular disease. In healthy individuals, plasma Hcy is between 5 and 10 micromol/L. One cause of severe hypehomocys- teinemia (HHcy) is the deficiency of cystathionine beta-synthase (CBS), which converts Hcy to cystathionine. CBS homozygous deficiency results in severe HHcy with Hcy levels up to 100 to 500 micromol/L. Patients with severe HHcy usually present with neurological abnormalities, premature arteriosclerosis. It has been reported that lowering plasma Hcy improved endothelial dysfunction and reduced incidence of major adverse events after percutaneous coronary intervention. The mechanisms by which Hcy induces atherosclerosis are largely unknown. Several biological mechanisms have been proposed to explain cardiovascular pathological changes associated with HHcy. These include: (1) endothelial cell damage and impaired endothelial function; (2) dysregulation of cholesterol and triglyceride biosynthesis; (3) stimulation of vascular smooth muscle cell proliferation; (4) thrombosis activation and (5) activation of monocytes. Four major biochemical mechanisms have been proposed to explain the vascular pathology of Hcy. These include: (1) autooxidation through the production of reactive oxygen species; (2) hypomethylation by forming SAH, a potent inhibitor of biological transmethylations; (3) nitrosylation by binding to nitric oxide or (4) protein homocysteinylation by incorporating into protein. In summary, our studies, as well as data from other laboratories support the concept that Hcy is causally linked to atherosclerosis, and is not merely associated with the disease. Although folic acid, vitamin B12 and B6 can lower plasma Hcy levels, the long-term effects on cardiovascular disease risk are still unknown and judgments about therapeutic benefits await the findings of ongoing clinical trials.
Animals ; Atherosclerosis ; etiology ; physiopathology ; Cystathionine beta-Synthase ; deficiency ; genetics ; Homocysteine ; metabolism ; Humans ; Hyperhomocysteinemia ; complications ; physiopathology ; Reactive Oxygen Species ; metabolism

BACKGROUND/AIMS: Halitosis is a symptom that bothers patients more socially than medically and its pathogenic mechanisms are unclear and treatment armamenterium is limited. Clinicians generally ignored active interventions. Since halitosis is closely associated with volatile sulfur compounds (VSCs), we used a Halimeter and gas chromatography to measure VSCs in patients with Helicobacter-pylori (H. pylori)-associated gastric diseases. METHODS: We categorized 72 patients with H. pylori infection into two groups based on their endoscopic findings: a non-erosive mucosal group (NE, n=24) and an erosive mucosal group (E, n=48). Halitosis was objectively assessed by applying either a Halimeter to breath air or gas chromatography to gastric juice. Simultaneously, the expression of VSC-generating enzyme was measured with reverse-transcriptase PCR using mRNA isolated from biopsy tissues. RESULTS: The levels of VSCs in exhaled breaths or aspirated gastric juices differed significantly between the NE and E groups (p<0.00001), suggesting that VSCs might reflect eroded epithelial damage induced by H. pylori infection. The expressions of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) were broadly consistent with the degree of mucosal injury. CONCLUSIONS: Erosive changes in esophagogastroduodenal mucosa were strongly correlated with increased VSC levels, suggesting that halitosis might result from H. pylori-associated erosive lesions.
Biopsy ; Chromatography, Gas ; Cystathionine beta-Synthase ; Cystathionine gamma-Lyase ; Cytochrome P-450 CYP1A1 ; Gastric Juice ; Halitosis ; Humans ; Hydrogen Sulfide ; Mucous Membrane ; Polymerase Chain Reaction ; RNA, Messenger ; Stomach Diseases ; Sulfur ; Sulfur Compounds

The present study was designed to investigate the potential role of endogenous hydrogen sulfide (H2S) in chronic stress-induced colonic hypermotility. Male Wistar rats were submitted daily to 1 h of water avoidance stress (WAS) or sham WAS (SWAS) for 10 consecutive days. The total number of fecal pellets was counted at the end of each 1 h of WAS or SWAS session. Organ bath recordings were used to test the colonic motility. H₂S production of colon was determined, and immunohistochemistry and Western blot were performed on rat colonic samples to detect the distribution and expression of H₂S-producing enzymes. The results showed that i) repeated WAS increased the number of fecal pellets per hour and the area under the curve (AUC) of the spontaneous contractions of colonic strips (P < 0.05), ii) repeated WAS decreased the endogenous production of H₂S and the expression of H₂S-producing enzymes in the colon devoid of mucosa and submucosa (P < 0.001), iii) cystathionine-γ-lyase (CSE) was strongly expressed in the cytosols of the circular and longitudinal smooth muscle cells and the nucleus of the myenteric plexus neurons, iv) cystathionine-&beta;-synthase (CBS) was primarily localized in the cytosols of myenteric plexus neurons and weakly localized in the epithelial cells and v) inhibitors of H₂S-producing enzymes increased the contractile activity of colonic strips in the SWAS rats (P < 0.001). In conclusion, the results suggest that the colonic hypermotility induced by repeated WAS may be associated with the decreased production of endogenous H2S.
Animals ; Colon ; physiopathology ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Gastrointestinal Motility ; Hydrogen Sulfide ; metabolism ; Male ; Muscle Contraction ; Myocytes, Smooth Muscle ; metabolism ; Neurons ; metabolism ; Rats ; Rats, Wistar ; Stress, Physiological