Biomod/2014/UANL/MedicalApplication

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Applications

The nanoreactor is designed to carry out enzyme reactions, releasing compounds useful for each application. In this case we will handle only two applications: Biomedical and Industrial.

Medical Application

Many millions of years ago, most mammals had a system for regulating uric acid in blood thus preventing the accumulation of this. This system decompose uric acid , a waste product of purine degradation into allantoin and peroxide involving an enzyme called uricase. Allantoin is 100 times more water soluble than uric acid , so it was easy for the mammal metabolism to dispose it ,preventing high product concentration.



























Fig. 1

It has now been found that higher mammals, such as primates and humans, lack this enzyme because in the evolutionary process happen a mutation in the gene encoding this protein . The mutation was found in three codons (33, 183, and exon 3) being in humans, orangutans and chimpanzees.

























Fig. 1

There are several theories which explain why this enzyme was lost, . The most succesful theorie says that the antioxidant system of the body with the participation of the enzymes superoxide dismutase and glutathione dismutase, these enzymes prevent oxidative damage in aging cells ,preventing various diseases. It is believed that the uricase degrading the the uric acid, produced large quantities of peroxide oxidants and metabolites, causing the accumulation of these by the shortage of antioxidant enzymes. The disappearance of this enzyme led to the longevity of the organism to accumulate as many non-oxidative products.

The project consists of the design of nanoreactor compatible with the human body with the goal to decompose the uric acid in the human body into more soluble and easy to remove compounds such as allantoin, water and oxygen. The action site is in the kidney, specifically in the afferent glomerular artery, this in order that the reaction happens before passing through the filtration bowman's capsule.

The nephropaty caused by the excess of uric acid , the urate oxidase transform the uric acid in allantoin which is more soluble in urine. The admnistration of exogen urate oxidase decreases the uric acid levels on serum and urine.



Enzymes

The main enzyme involved in the degradation of uric acid is uricase, is distinguished by having a high affinity to uric acid. It has a high oxidizing power. Depending on the conditions it can give different compounds such as Alioxan, Uroxanic acid, Uric acid glycol ,Allantoin causingin all reactions peroxide which will be offset by the second enzyme system, catalase.

As already mentioned, it is intended that the reaction form allantoin which is more soluble than urate. It has been found that in 95% to 100% of cases being uricase in the presence of catalase the reactions takes the path of production of allantoin this is why the nanoreactor, apart from isolating the reaction provides peroxide leakage protection, prevents the formation of other oxidizing components as they can provoke a serious problem in cell.

Reaction:

















Expected Results

The uric acid enter the nanoreactor and a series of reactions catalyzed by enzymes will happen, products exit through diffusion. The reaction produces allantoin thanks to the catalase ,water and oxygen.The Allantoin and water will be filtered by the glomerulus while oxygen pass to portal circulation.


References:

[1] Alvares, K., Widrow, R. J., Abu-Jawdeh, G. M., Schmidt, J. V., Yeldandi, A. V., Rao, M. S., & Reddy, K. J. (1992). Rat urate oxidase produced by recombinant baculovirus expression: Formation of peroxisome crystalloid core-like structures. Proc. Nati. Acad. Sci. USA, 4908-4912.

[2] Chelikani, P., Fita, I., & Loewen, P. (2004). Diversity of structures and properties among catalases. Cell. Mol. Life Sci., 192-208.

[3] I., C. A. (03 de Mayo de 2011). Biología y Salud. Obtenido de Déficit de hipoxantina-guanina fosforribosiltransferasa. Síndrome de Lesch-Nyhan.: http://www.biopsicologia.net/el-proyecto/nivel-4-patologias/1093-2112-deficit-de-hipoxantina-guanina-fosforribosiltransferasa-sindrome-de-lesch-nyhan

[4] Motojima, K., Kanaya, S., & Goto , S. (1988). Cloning and SequenceA nalysis of cDNA for Rat and Liver Uricase. The Journal of Biological Chemistry, 16677-16681.

[5] Torres Jiménez, R., & García Puig, J. (18 de Octubre de 2014). Enfermedades Raras. Obtenido de Síndrome de Kelley-Seegmiller: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=ES&Expert=79233

[6] Werner, M.-E. (2008). Bioquímica: Fundamentos para Medicina y Ciencias de la Vida. Barcelona, España: Reverté.

[7] Wu, X., Chi, L. C., Muzny, D. M., & Caskey, T. C. (1989). Urate oxidase: Primary structure and evolutionary implications. Proc. Nati. Acad. Sci. USA, 9412-9416.

[8] http://www.medscape.com/viewarticle/734579_2http://www.medscape.com/viewarticle/734579_2

[9] Uricase based methods for determination of uric acid in serum Yunsheng Zhao & Xiaoyan Yang & Wei Lu & Hong Liao & Fei Liao

[10] http://www.kidneypathology.com/Histologia_glomerulo.html

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