Citrate inhibition of snake venom proteases

Odell, George V.; Ferry, Peggy C.; Vick, L.M; Fenton, Aron W.; Decker, L.S; Cowell, Rick L.; Ownby, Charlotte L.; Gutiérrez, José Marı́a

doi:10.1016/s0041-0101(98)00084-1

Cited by 49 publications

(29 citation statements)

References 9 publications

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“…1). The increase in amino acids like serine, glycine, and arginine may be explained by proteolysis (30 ) that is partly inhibited by anticoagulants like EDTA (38 ), heparin (39 ), and citrate (40 ).…”

Section: Possible Mechanismsmentioning

confidence: 99%

Kinetic Modeling of Storage Effects on Biomarkers Related to B Vitamin Status and One-Carbon Metabolism

et al. 2012

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BACKGROUND Biomarkers and metabolites related to B vitamin function and one-carbon metabolism have been studied as predictors of chronic diseases in studies based on samples stored in biobanks. For most biomarkers, stability data are lacking or fragmentary. METHODS Degradation and accumulation kinetics of 32 biomarkers were determined at 23 °C in serum and plasma (EDTA, heparin, and citrate) collected from 16 individuals and stored for up to 8 days. In frozen serum (−25 °C), stability was studied cross-sectionally in 650 archival samples stored for up to 29 years. Concentration vs time curves were fitted to monoexponential, biexponential, linear, and nonlinear models. RESULTS For many biomarkers, stability was highest in EDTA plasma. Storage effects were similar at room temperature and at −25 °C; notable exceptions were methionine, which could be recovered as methionine sulfoxide, and cystathionine, which decreased in frozen samples. Cobalamin, betaine, dimethylglycine, sarcosine, total homocysteine, total cysteine, tryptophan, asymetric and symmetric dimethyl argenine, creatinine, and methylmalonic acid were essentially stable under all conditions. Most B vitamins (folate and vitamins B2 and B6) were unstable; choline increased markedly, and some amino acids also increased, particularly in serum. The kynurenines showed variable stability. For many biomarkers, degradation (folate and flavin mononucleotide) or accumulation (pyridoxal, riboflavin, choline, amino acids) kinetics at room temperature were non–first order. CONCLUSIONS Data on stability and deterioration kinetics for individual biomarkers are required to optimize procedures for handling serum and plasma, and for addressing preanalytical bias in epidemiological and clinical studies.

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Section: Possible Mechanismsmentioning

confidence: 99%

Kinetic Modeling of Storage Effects on Biomarkers Related to B Vitamin Status and One-Carbon Metabolism

et al. 2012

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“…Likewise, snake venom proteomes are highly complex and their protein integrity control and maintenance of homeostasis within the gland lumen, are crucial for the expression of biological activities, which favor the survival of the snake in its particular environment. In the gland lumen widespread, random proteolysis of venom components is minimized by the acidic pH which does not favor the activity of metalloproteinases (SVMPs) 1 and serine proteinases (SVSPs) (3). Moreover, the presence of pyro-glutamate containing tripeptides in the venomous secretion contributes to the lack of proteolytic activity of SVMPs and prevents extensive degradation of venom components (4).…”

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confidence: 99%

Peptidomics of Three Bothrops Snake Venoms: Insights Into the Molecular Diversification of Proteomes and Peptidomes

Tashima

Zelanis

Kitano

et al. 2012

Molecular & Cellular Proteomics

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Snake venom proteomes/peptidomes are highly complex and maintenance of their integrity within the gland lumen is crucial for the expression of toxin activities. There has been considerable progress in the field of venom proteomics, however, peptidomics does not progress as fast, because of the lack of comprehensive venom sequence databases for analysis of MS data. Therefore, in many cases venom peptides have to be sequenced manually by MS/MS analysis or Edman degradation. This is critical for rare snake species, as is the case of Bothrops cotiara (BC) and B. fonsecai (BF), which are regarded as near threatened with extinction. In this study we conducted a comprehensive analysis of the venom peptidomes of BC, BF, and B. jararaca (BJ) using a combination of solid-phase extraction and reversed-phase HPLC to fractionate the peptides, followed by nano-liquid chromatography-tandem MS (LC-MS/MS) or direct infusion electrospray ionization-(ESI)-MS/MS or MALDI-MS/MS analyses. We detected marked differences in the venom peptidomes and identified peptides ranging from 7 to 39 residues in length by de novo sequencing. Forty-four unique sequences were manually identified, out of which 30 are new peptides, including 17 bradykinin-potentiating peptides, three poly-histidine-poly-glycine peptides and interestingly, 10 L-amino acid oxidase fragments. Some of the new bradykinin-potentiating peptides display significant bradykinin potentiating activity. Automated database search revealed fragments from several toxins in the peptidomes, mainly from L-amino acid oxidase, and allowed the determination of the peptide bond specificity of proteinases and amino acid occurrences for the P4-P4 sites. We also demonstrate that the venom lyophilization/resolubilization process greatly increases the complexity of the peptidome because of the imbalance caused to the venom proteome and the consequent activity of proteinases on venom components. The use of proteinase inhibitors clearly showed different outcomes in the peptidome characterization and suggested that degradomic-peptidomic analysis of snake venoms is highly sensitive to the conditions of sampling procedures. Molecular & Cellular Proteomics 11: 10.1074/mcp.M112.019331, 1245-1262, 2012.Snake venoms are the products of specialized secretory glands located above the upper jawbone in venomous snakes. Like most secretory proteins, venom toxins are synthesized in the cytoplasm of secretory cells in the gland and transferred to the rough endoplasmic reticulum, then to the Golgi apparatus, and finally transported via secretory granules to the lumen of the venom gland (1). The snake venomous secretion is an aqueous solution containing a high amount of proteins and peptides, however the mechanisms for controlling protein secretion into the gland lumen and for regulating its protein/peptide concentration, ionic strength, and pH are unknown. As in all eukaryotic cells the proteomes of the venom gland tissue are highly complex, comprising a much great number and diversity of multidomain proteins (2...

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“…Eventually the patient's renal recovery was sufficient to discontinue hemodialysis, and he was discharged home on hospital day 30. experiencing envenomation associated coagulopathies. Addition of exogenous citrate has been shown in vitro to inhibit venom protease activity via chelation with zinc in zinc-dependent enzymes, however to a far less extent with the Crotalinae subfamily compared to other vipers, such as the Bothrops genus (7.8 vs. 75%) [17]. Further studies and reports could further assess benefits of citrate anticoagulation in patients requiring CRRT after envenomation with various viper species.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Coagulopathy Following Rattlesnake Envenomation Responsive to Antivenom: A Case Report

Roberts¹

2017

Int Arch Clin Pharmacol

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Citrate inhibition of snake venom proteases

Cited by 49 publications

References 9 publications

Kinetic Modeling of Storage Effects on Biomarkers Related to B Vitamin Status and One-Carbon Metabolism

Kinetic Modeling of Storage Effects on Biomarkers Related to B Vitamin Status and One-Carbon Metabolism

Peptidomics of Three Bothrops Snake Venoms: Insights Into the Molecular Diversification of Proteomes and Peptidomes

Prolonged Coagulopathy Following Rattlesnake Envenomation Responsive to Antivenom: A Case Report

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