Disease relevance of PAG

• Furthermore, propargylglycine prevented L-cysteine cytoprotection against cyanide toxicity [1].
• When the dose of D,L-propargylglycine was 50 mg/kg of body weight, the increase of gamma-Glu-PPG-Gly was proportional to the time after the administration of D,L-propargylglycine, up to 8 h, and then gradually decreased to about 50% of the maximum at 24 h, where the maximum level of gamma-Glu-PPG-Gly at 8 h was 1.15 +/- 0.08 micromol/g of liver [2].
• Inhibition effect of propargylglycine on human fibrosarcoma HT-1080 cell invasiveness [3].

High impact information on PAG

• Injection of propargylglycine, an inhibitor of cystathionase, decreased MT induction by zinc in the tumor and diminished the resistance to these drugs [4].
• Blockade of the transsulfuration pathway with propargylglycine suppressed clearance of M. smegmatis by macrophages and inhibited phagolysosomal fusion, whereas N-acetylcysteine promoted phagolysosomal fusion and enhanced mycobacterial clearance 3-fold compared with untreated cells [5].
• Lowering endogenous H2S level with, D,L-propargylglycine and beta-cyano-L-alanine, two CSE inhibitors, significantly decreased [Ca2+]i, suggesting that endogenous H2S may have a positive tonic influence on [Ca2+]i homeostasis [6].
• All the changes mentioned above also happen in the lactating mammary gland when propargylglycine, an inhibitor of the liver trans-sulphuration pathway, is administered [7].
• A series of carboxylic acids were prepared from a propargylglycine scaffold and tested for efficacy as matrix metalloproteinase (MMP) inhibitors [8].

Chemical compound and disease context of PAG

• Contents of cystathionine in the liver increased gradually from 0.25 mg to 30 mg/200 g body weight in proportion to the amounts of D,L-propargylglycine injected; in the kidney, 0.5 mg to 10 mg; in the brain, 5 mg to 20 mg; in the serum, 0.25 mg to 30 mg [9].

Biological context of PAG

• These results suggest a role for MT in drug resistance in tumors, and injection of propargylglycine may provide a potential means to overcome drug resistance caused by elevation of MT levels in certain tumors [4].
• Inhibition of liver trans-sulphuration pathway by propargylglycine mimics gene expression changes found in the mammary gland of weaned lactating rats: role of glutathione [7].
• The LD50 of cyanide in rats treated with propargylglycine was 5.14 +/- 0.029 mg NaCN/kg, which was significantly (P < 0.05) lower than the 5.98 +/- 0.008 mg NaCN/kg LD50 of cyanide determined in control rats [10].
• Inhibition of glutathione synthesis with propargylglycine enhances N-acetylmethionine protection and methylation in bromobenzene-treated Syrian hamsters [11].
• Liver gamma-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation [12].

Anatomical context of PAG

• Amino-oxyacetate (AOA) (1 mM) abolished H2S production in liver tissues and partially inhibited H2S production in the ileum, while D,L-propargylglycine (PPG) at a similar concentration only slightly inhibited H2S production in liver [13].
• The apparent Km value of gamma-Glu-PPG-Gly formation in human erythrocytes for D,L-propargylglycine was 0.32 mM [14].

Associations of PAG with other chemical compounds

• Second, propargylglycine, a mechanism-based inactivator of cystathionine gamma-lyase in vitro, inhibits the synthesis of thienamycin in vivo [15].
• Our pilot experiment suggests a possible role for endogenous hydrogen sulphide in erectile physiopharmacology through facilitation of nerve-mediated penile tumescence; this is confirmed by the inhibitory effect of propargylglycine on the proerectile pathway [16].
• To study the fate of L-cysteine and amino acid homeostasis in liver after the inhibition of the trans-sulfuration pathway, rats were treated with propargylglycine (PPG) [17].
• Determination of D,L-propargylglycine and N-acetylpropargylglycine in urine and several tissues of D,L-propargylglycine-treated rats using liquid chromatography-mass spectrometry [18].
• Aviglycine and propargylglycine inhibit conidial germination and mycelial growth of Fusarium oxysporumf. sp. luffae [19].

Gene context of PAG

• Incubation with an inhibitor of gamma-cystathionase (propargylglycine) prevented inactivation of tyrosine aminotransferase [20].
• A yeast strain highly resistant to propargylglycine (an inhibitor of cystathionine gamma-lyase) was isolated from air [21].
• Hepatic gamma-cystathionase activity at 12 h after the intraperitoneal injection decreased in proportion to the amount of D,L-propargylglycine administered, but hepatic cystathionine beta-synthase activity did not change [9].
• Mechanism of inactivation of gamma-cystathionase by the acetylenic substrate analogue propargylglycine [22].
• However, inhibition of the cystathionase pathway in newborn rats with propargylglycine decreased hepatic levels of MT, zinc and GSH [23].

Analytical, diagnostic and therapeutic context of PAG

• However, injection of PPG, an inhibitor of cystathionase, decreased the zinc-induced MT synthesis in the tumors and also decreased the tumor weight after exposure to X radiation [24].
• An experimental animal model with cystathioninuria was obtained by the injection of D,L-propargylglycine into rats [18].
• Rats were fed a diet containing both methionine (0.66%) and cystine (0.20%) for 1 week before receiving three consecutive daily intraperitoneal injections of propargylglycine, a selective cystathionase inhibitor, at various doses (2.5-375 mumol/kg) [25].
• Methods: The ASMCs were divided into the following groups: (1) the control group; (2) the zinc protoporphyrin (ZnPP) 20 mumol/L group; (3) the propargylglycine (PPG) 2 mmol/L, 4 mmol/L and 10 mmol/L groups; and (4) the sodium hydrosulfide (NaHS) 1x10(-5) mol/L, 1x10(-4) mol/L and 1x10(-3) mol/L groups [26].

References