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

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

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

Cystathionine is well-known intermediate in the metabolism of methionine. It is cleaved to cysteine and homoserine by gamma-cystathionase. This enzyme utilize pyridoxal 5'-phosphate as coenzyme. gamma-cystathionase deficiency leads to persistent excretion of large amount of cystathionine in urine, as well as to accumulation of cystathionine in body tissues and fluids. It is inherited as an autosomal recessive trait and shows wide variety of clinical manifestations. No clinical abnormality seems to be specifically associated with gamma-cystathionase deficiency. The majority of patients responded to high dose administration of pyridoxine. We report the first case of cystathioninuric patient in Korea, 19 months of female with developmental delay. In brain MRI, there was generalized mild brain atrophy. There were several times of brief paroxysmal generalized polyspike and wave discharges in electroencephalography(EEG). In amino acid analysis of urine, there was elevated level of cystathionine. She was treated with high dose of pyridoxine. In follow up analysis of urinary amino acid, the cystathionine level was markedly decreased to normal range, and EEG was normalized. Her development shows improvement.
Atrophy ; Brain ; Cystathionine ; Cystathionine gamma-Lyase ; Cysteine ; Electroencephalography ; Female ; Follow-Up Studies ; Homoserine ; Humans ; Korea ; Magnetic Resonance Imaging ; Metabolism ; Methionine ; Pyridoxal ; Pyridoxine ; Reference Values

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 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

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

Animals ; Arteries ; metabolism ; Cochlea ; blood supply ; Cystathionine gamma-Lyase ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To study the change of endogenous hydrogen sulfide (hydrogen sulfide, H2S) and its rate-limiting enzyme Cystathionine-gamma-lyase (CSE) in allergic rhinitis through guinea pigs with intervention treatment. METHOD: Twenty-four guinea pigs were divide into 4 groups at random, one group were models of allergic rhinitis (AR) which were established by using ovalbumin, the second group were treated with NaHS after sensitized, the third group were treated with Propargylglycine (PPG) which was suppression of CSE after sensitized, and the last group were treated with saline for control. The concentration of eotaxin of nasal lavage and H2S in plasma were recorded, and then the expression of CSE in nasal mucosa was determined by real-time fluorescence RT-PCR. RESULT: The concentration of eotaxin in nasal lavage of sensitized group were higher than those of control (P < 0.01), and concentration of H2S in plasma and expression of CSE in nasal mucosa were lower than control (P < 0.05). The concentration of eotaxin decreased when treated with NaHS and increased when treated with PGG (P < 0.05). Level of H2S in plasma and expression of CSE increased when treated with NaHS and decreased when treated with PGG (P < 0.05), and the level of H2S was positive linear correlate with the expression of CSE. CONCLUSION Endogenous H2S perhaps plays a significant role in the pathogenesis of allergic rhinitis, and it was mainly regulated by CSE.
Animals ; Cystathionine gamma-Lyase ; metabolism ; Guinea Pigs ; Hydrogen Sulfide ; metabolism ; Male ; Nasal Mucosa ; metabolism ; Rhinitis ; metabolism