Team:Brasil-SP/Project/Cystatin

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<h1>Cystatin C</h1>
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Cystatin C (Cys C) is an inhibitor of cysteine proteases that has 120 amino acid residues and is produced by all nucleated cells. It is an excellent biomarker for renal dysfunction, specially for Chronic Kidney Disease (CDK), due to its constant rate in the blood and its independence of the aforementioned variables (diet, gender, ethnicity, age, muscle mass, and others), varying only with changes in the glomerular filtration rate (GFR). More specifically, Cys C levels rises when GFR descreases and falls when the GFR increases (ABRAHAMSON, 2014; SARKAR et al, 2005; WASUNG et al, 2014).
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In order to work with a system capable of detecting a inhibitor like Cys C, we looked for an enzyme that has its activity inhibited specifically by the Cys C so that we could measure the Cys C levels through alteration in the enzyme activity. Several scientific studies have shown that Cystatin C has inhibitory activity against Papain and Cathepsin S, which is illustrated in the following table (ABRAHAMSON, 2014; WASUNG et al, 2014).
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<h2>Crystallografic Structure of Human Cystatin C</h2>
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<h3>References</h3>
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#ABRAHAMSON M. Cystatins. <b>Methods in Enzymology</b>, 1994, 240: 685-700.
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#SARKAR PD, RAJESHWARI G, SHIVAPRAKASH TM. Cystatin C - a novel marker of glomerular filtration rate. <b>Indian Journal of Clinical Biochemistry</b>, 2005, 20(1):139-144. doi: 10.1007/BF02893060.
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#WASUNG ME, CHAWLA LS, MADERO M. Biomarkers of renal function, which and when? <b>Clinica Chimica Acta</b>, 2014, pii:S0009-8981(14):00391-X. doi: 10.1016/j.cca.2014.08.039.
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#http://www.rcsb.org/pdb/explore/explore.do?structureId=3GAX
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<h3 align="center">Cystatin C</h3>
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<p><div align="justify">Cystatin C, an inhibitor of cysteine proteases, has 120 amino acid residues and it is produced by all nucleated cells. It is an excellent biomarker for renal dysfunction due to its constant rate in the blood and its independence of the aforementioned variables (diet, gender, ethnicity, age, muscle mass, and others). Several scientific studies showed that Cystatin C has inhibitory activity against Papain and Calpain II.
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Cystatin C, likewise other low molecular weight proteins, is freely filtered by the glomeruli and it is almost completely reabsorbed in the proximal tubules. The level of Cystatin C remain constant when its production is equivalent to the nonreabsorbed portion. In patients with renal dysfunction, the GFR is lower because a smaller amount of filtered blood is filtered; as a consequence, a smaller amount of Cystatin C is reabsorbed by the proximal tubules, resulting in lower levels of excreted Cystatin C. Logically, a decrease in GFR implies an increase of Cystatin C concentration in the blood. Thus, the Cystatin C concentration in the blood is totally dependent on the GFR.</div></p>
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Latest revision as of 23:57, 17 October 2014

TheProjectBRASILSP.png

Cystatin C

Cystatin C (Cys C) is an inhibitor of cysteine proteases that has 120 amino acid residues and is produced by all nucleated cells. It is an excellent biomarker for renal dysfunction, specially for Chronic Kidney Disease (CDK), due to its constant rate in the blood and its independence of the aforementioned variables (diet, gender, ethnicity, age, muscle mass, and others), varying only with changes in the glomerular filtration rate (GFR). More specifically, Cys C levels rises when GFR descreases and falls when the GFR increases (ABRAHAMSON, 2014; SARKAR et al, 2005; WASUNG et al, 2014).

In order to work with a system capable of detecting a inhibitor like Cys C, we looked for an enzyme that has its activity inhibited specifically by the Cys C so that we could measure the Cys C levels through alteration in the enzyme activity. Several scientific studies have shown that Cystatin C has inhibitory activity against Papain and Cathepsin S, which is illustrated in the following table (ABRAHAMSON, 2014; WASUNG et al, 2014).

CysC table.png
ABRAHAMSON,1994.

Crystallografic Structure of Human Cystatin C


Crystal structure of human cystatin C.png
Crystallografic Structure of Human Cystatin C - Ref. [4]

References

  1. ABRAHAMSON M. Cystatins. Methods in Enzymology, 1994, 240: 685-700.
  2. SARKAR PD, RAJESHWARI G, SHIVAPRAKASH TM. Cystatin C - a novel marker of glomerular filtration rate. Indian Journal of Clinical Biochemistry, 2005, 20(1):139-144. doi: 10.1007/BF02893060.
  3. WASUNG ME, CHAWLA LS, MADERO M. Biomarkers of renal function, which and when? Clinica Chimica Acta, 2014, pii:S0009-8981(14):00391-X. doi: 10.1016/j.cca.2014.08.039.
  4. http://www.rcsb.org/pdb/explore/explore.do?structureId=3GAX

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