Glikacija

Glikacija (ponekad pogrešno zvana neenzimska glikozilacija) je kovalentno vezivanje šećera za protein ili lipid. ^[1] Tipski šećeri koji sudjeluju u glikaciji su glukoza, fruktoza i njihovi derivati. Glikacija je neenzimski proces odgovoran za mnoge (npr. mikro- i makrovaskularne) komplikacije kod diabetes mellitus i uključen je u neke bolesti i starenje.^[2]^[3]^[4] Vjeruje se da krajnji proizvodi glikacije imaju uzročnu ulogu u vaskularnim komplikacijama diabetes mellitus. ^[5]

Za razliku od glikacije, glikozilacija je enzimski posredovano ATP-zavisno vezivanje šećera za proteine ili lipide.^[1] Glikozilacija se javlja na određenim mjestima na ciljnoj molekuli. To je uobičajen oblik posttranslacijske modifikacije proteina i potreban je za funkcioniranje zrelog proteina.

Biohemija

Glikacijski put putem Amadorijevog preuređenja (u HbA1c, R je tipski N-terminalni valin). ^[6]

Imidazoloni (R = CH₂CH(OH)CH(OH)CH₂OH) su tipski produkti glikacije. Nastaju kondenzacijom 3-deoksiglukozona s gvanidinskom grupom ostatka arginina.^[7]

Glikacije se javljaju uglavnom u krvotoku, do malog udjela apsorbiranih jednostavnih šećera: glukoza, fruktoza i galaktoza. Čini se da fruktoza ima približno deset puta veću aktivnost glikacije od glukoze, primarnog tjelesnog goriva.^[8] Glikacija se može pojaviti putem Amadori reakcija, Schiffovih baznih reakcija i Millardovim reakcijama, koje dovode do naprednih krajnjih proizvoda glikacije (AGE-i).^[1]

Biomedicinske implikacije

Crvena krvna zrnca imaju dosljedan životni vijek od 120 dana i dostupna su za mjerenje glikiranog hemoglobina. Mjerenje HbA1c – dominantnog oblika glikiranog hemoglobina – omogućuje praćenje srednjeročne kontrole šećera u krvi kod dijabetesa.

Neki proizvodi glikacije uključeni su u mnoge hronične bolesti povezane sa starenjem. Glikacijske kardiovaskularne bolesti (oštećenja endotela, fibrinogena i kolagena), Alzheimerova bolest (amiloidni proteini su nusproizvodi reakcija koje napreduju do AGE-a).^[9]^[10]

Dugovječne ćelije (kao što su živci i različiti tipovi moždanih ćelijaa), dugotrajni proteini (kao što su kristalaste leće i rožnjača) i DNK može s vremenom održavati značajnu glikaciju. Oštećenje glikacijom rezultira učvršćivanjem kolagena u zidovima krvnih žila, što dovodi do visokog krvnog pritiska, posebno kod dijabetesa.^[11] Glikacija također uzrokuje slabljenje kolagena u stijenkama krvnih žila,^[12] što može dovesti do mikro- ili makroaneurizme; to može uzrokovati moždane udare ako se nalazi u mozgu

Također pogledajte

Reference

^ ^a ^b ^c Lima, M.; Baynes, J. W. (2013-01-01), "Glycation", u Lennarz, William J.; Lane, M. Daniel (ured.), Encyclopedia of Biological Chemistry (Second Edition) (jezik: engleski), Waltham: Academic Press, str. 405–411, doi:10.1016/b978-0-12-378630-2.00120-1, ISBN 978-0-12-378631-9, pristupljeno 2020-12-16
^ Glenn, J.; Stitt, A. (2009). "The role of advanced glycation end products in retinal ageing and disease". Biochimica et Biophysica Acta (BBA) - General Subjects. 1790 (10): 1109–1116. doi:10.1016/j.bbagen.2009.04.016. PMID 19409449.
^ Semba, R. D.; Ferrucci, L.; Sun, K.; Beck, J.; Dalal, M.; Varadhan, R.; Walston, J.; Guralnik, J. M.; Fried, L. P. (2009). "Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women". Aging Clinical and Experimental Research. 21 (2): 182–190. doi:10.1007/BF03325227. PMC 2684987. PMID 19448391.
^ Semba, R.; Najjar, S.; Sun, K.; Lakatta, E.; Ferrucci, L. (2009). "Serum carboxymethyl-lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults". American Journal of Hypertension. 22 (1): 74–79. doi:10.1038/ajh.2008.320. PMC 2637811. PMID 19023277.
^ Yan, S. F.; D'Agati, V.; Schmidt, A. M.; Ramasamy, R. (2007). "Receptor for Advanced Glycation Endproducts (RAGE): a formidable force in the pathogenesis of the cardiovascular complications of diabetes & aging". Current Molecular Medicine. 7 (8): 699–710. doi:10.2174/156652407783220732. PMID 18331228.
^ Yaylayan, Varoujan A.; Huyghues-Despointes, Alexis (1994). "Chemistry of Amadori Rearrangement Products: Analysis, Synthesis, Kinetics, Reactions, and Spectroscopic Properties". Critical Reviews in Food Science and Nutrition. 34 (4): 321–69. doi:10.1080/10408399409527667. PMID 7945894.
^ Bellier, Justine; Nokin, Marie-Julie; Lardé, Eva; Karoyan, Philippe; Peulen, Olivier; Castronovo, Vincent; Bellahcène, Akeila (2019). "Methylglyoxal, a Potent Inducer of AGEs, Connects between Diabetes and Cancer". Diabetes Research and Clinical Practice. 148: 200–211. doi:10.1016/j.diabres.2019.01.002. PMID 30664892.
^ McPherson JD, Shilton BH, Walton DJ (March 1988). "Role of fructose in glycation and cross-linking of proteins". Biochemistry. 27 (6): 1901–7. doi:10.1021/bi00406a016. PMID 3132203.
^ Münch, Gerald; et al. (27 February 1997). "Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of β-amyloid peptide". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1360 (1): 17–29. doi:10.1016/S0925-4439(96)00062-2. PMID 9061036.
^ Munch, G; Deuther-Conrad W; Gasic-Milenkovic J. (2002). "Glycoxidative stress creates a vicious cycle of neurodegeneration in Alzheimer's disease--a target for neuroprotective treatment strategies?". J Neural Transm Suppl. 62 (62): 303–307. doi:10.1007/978-3-7091-6139-5_28. PMID 12456073.
^ Soldatos, G.; Cooper ME (Dec 2006). "Advanced glycation end products and vascular structure and function". Curr Hypertens Rep. 8 (6): 472–478. doi:10.1007/s11906-006-0025-8. PMID 17087858. S2CID 31239347.
^ Lee, J. Michael; Samuel P. Veres (2019-04-02). "Advanced glycation end-product cross-linking inhibits biomechanical plasticity and characteristic failure morphology of native tendon". Journal of Applied Physiology. 126 (4): 832–841. doi:10.1152/japplphysiol.00430.2018. PMC 6485690. PMID 30653412.

Dopunska literatura

Ahmed N, Furth AJ (July 1992). "Failure of common glycation assays to detect glycation by fructose". Clin. Chem. 38 (7): 1301–3. doi:10.1093/clinchem/38.7.1301. PMID 1623595.
Vlassara H (June 2005). "Advanced glycation in health and disease: role of the modern environment". Annals of the New York Academy of Sciences. 1043 (1): 452–60. Bibcode:2005NYASA1043..452V. doi:10.1196/annals.1333.051. PMID 16037266. S2CID 20952378.

[:0-1] Lima, M.; Baynes, J. W. (2013-01-01), "Glycation", u Lennarz, William J.; Lane, M. Daniel (ured.), Encyclopedia of Biological Chemistry (Second Edition) (jezik: engleski), Waltham: Academic Press, str. 405–411, doi:10.1016/b978-0-12-378630-2.00120-1, ISBN 978-0-12-378631-9, pristupljeno 2020-12-16

[2] Glenn, J.; Stitt, A. (2009). "The role of advanced glycation end products in retinal ageing and disease". Biochimica et Biophysica Acta (BBA) - General Subjects. 1790 (10): 1109–1116. doi:10.1016/j.bbagen.2009.04.016. PMID 19409449.

[3] Semba, R. D.; Ferrucci, L.; Sun, K.; Beck, J.; Dalal, M.; Varadhan, R.; Walston, J.; Guralnik, J. M.; Fried, L. P. (2009). "Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community-dwelling women". Aging Clinical and Experimental Research. 21 (2): 182–190. doi:10.1007/BF03325227. PMC 2684987. PMID 19448391.

[4] Semba, R.; Najjar, S.; Sun, K.; Lakatta, E.; Ferrucci, L. (2009). "Serum carboxymethyl-lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults". American Journal of Hypertension. 22 (1): 74–79. doi:10.1038/ajh.2008.320. PMC 2637811. PMID 19023277.

[5] Yan, S. F.; D'Agati, V.; Schmidt, A. M.; Ramasamy, R. (2007). "Receptor for Advanced Glycation Endproducts (RAGE): a formidable force in the pathogenesis of the cardiovascular complications of diabetes & aging". Current Molecular Medicine. 7 (8): 699–710. doi:10.2174/156652407783220732. PMID 18331228.

[6] Yaylayan, Varoujan A.; Huyghues-Despointes, Alexis (1994). "Chemistry of Amadori Rearrangement Products: Analysis, Synthesis, Kinetics, Reactions, and Spectroscopic Properties". Critical Reviews in Food Science and Nutrition. 34 (4): 321–69. doi:10.1080/10408399409527667. PMID 7945894.

[DRCP-7] Bellier, Justine; Nokin, Marie-Julie; Lardé, Eva; Karoyan, Philippe; Peulen, Olivier; Castronovo, Vincent; Bellahcène, Akeila (2019). "Methylglyoxal, a Potent Inducer of AGEs, Connects between Diabetes and Cancer". Diabetes Research and Clinical Practice. 148: 200–211. doi:10.1016/j.diabres.2019.01.002. PMID 30664892.

[8] McPherson JD, Shilton BH, Walton DJ (March 1988). "Role of fructose in glycation and cross-linking of proteins". Biochemistry. 27 (6): 1901–7. doi:10.1021/bi00406a016. PMID 3132203.

[9] Münch, Gerald; et al. (27 February 1997). "Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of β-amyloid peptide". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1360 (1): 17–29. doi:10.1016/S0925-4439(96)00062-2. PMID 9061036.

[10] Munch, G; Deuther-Conrad W; Gasic-Milenkovic J. (2002). "Glycoxidative stress creates a vicious cycle of neurodegeneration in Alzheimer's disease--a target for neuroprotective treatment strategies?". J Neural Transm Suppl. 62 (62): 303–307. doi:10.1007/978-3-7091-6139-5_28. PMID 12456073.

[11] Soldatos, G.; Cooper ME (Dec 2006). "Advanced glycation end products and vascular structure and function". Curr Hypertens Rep. 8 (6): 472–478. doi:10.1007/s11906-006-0025-8. PMID 17087858. S2CID 31239347.

[12] Lee, J. Michael; Samuel P. Veres (2019-04-02). "Advanced glycation end-product cross-linking inhibits biomechanical plasticity and characteristic failure morphology of native tendon". Journal of Applied Physiology. 126 (4): 832–841. doi:10.1152/japplphysiol.00430.2018. PMC 6485690. PMID 30653412.

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