Advertisement

Pharmaceutical Enzymes

  • Deeplina Das
  • Arun GoyalEmail author
Chapter

Abstract

Enzymes are important in all living cells because they act as biological catalysts that accelerate chemical reactions without being consumed in the process. Enzymes are crucial elements of every living entity and also address the dominant underlying causes of several health problems. Pharmaceutically important enzymes are an important component of the pharmaceutical market. They are broadly defined as prodrugs that target a specific biological reversible or irreversible reaction to treat a particular disease. Microorganisms are major source of pharmaceutically important enzymes, but several enzymes are also obtained from animal and renewable plant sources. Enzymes which are used for pharmaceutical applications include cysteine proteinases, asparaginase, streptokinase, urokinase, deoxyribonuclease I, hyaluronidase, pegademase, and glucocerebrosidase. Immobilized enzymes are also used in pharmaceutical industry. In pharmaceutical industry, the major applications of immobilized enzymes are the production of 6-aminopenecillinic acid using immobilized penicillin amidase which helps in the deacylation of the side chain of either penicillin G or penicillin V. There are several benefits of enzymes immobilization such as cost-effectiveness, protection from degradation and deactivation, retention of enzyme, enhanced stability, recycling, and repetitive use. The industrially important enzymes, such as α-amylase, protease, and alkaline lipase, are required in large volumes, but have an inherently low unit value so that they demand significantly lower manufacturing cost. On the other hand, pharmaceutical enzymes are produced in lower volumes and have inherently higher manufacturing cost.

Keywords

Enzyme Replacement Therapy Fabry Disease Gauche Disease Orphan Drug Human Neutrophil Elastase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Aiuti A (2002) Advances in gene therapy for ADA-deficient SCID. Curr Opin Mol Ther 4:515–522Google Scholar
  2. Ali MA, Saleh FM, Das K et al (2011) Gaucher disease. Mymensingh Med J 20:490–492Google Scholar
  3. Alvaro G, Fernandez LR, Blanco RM et al (1990) Immobilization-stabilization of penicillin G acylase from Escherichia coli. Appl Biochem Biotechnol 26:181–195CrossRefGoogle Scholar
  4. Arshad R, Farooq S, Ali SS (2007) 6-Aminopenicillanic acid production by intact cells of E. coli containing penicillin G acylase (PGA). Pak J Biol Sci 10:3190–3194CrossRefGoogle Scholar
  5. Bond CS, Clements PR, Ashby SJ et al (1997) Structure of a human lysosomal sulfatase. Structure 5:277–289CrossRefGoogle Scholar
  6. Bradbury E, Moon L, Popat R et al (2002) Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416:636–640CrossRefGoogle Scholar
  7. Brien S, Lewith G, Walker A (2004) Bromelain as a treatment for osteoarthritis: a review of clinical studies. eCAM 1:251–257Google Scholar
  8. Capstick T, Henry MT (2005) Efficacy of thrombolytic agents in the treatment of pulmonary embolism. Eur Respir J 26:864–874CrossRefGoogle Scholar
  9. Chan B, Wara D, Bastian J et al (2005) Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID). Clin Immunol 117:133–143CrossRefGoogle Scholar
  10. Chu L, Robinson DK (2001) Industrial choices for protein production by large-scale cell culture. Curr Opin Biotechnol 12:180–187CrossRefGoogle Scholar
  11. Chughtai B, O'Riordan TG (2004) Potential role of inhibitors of neutrophil elastase in treating diseases of the airway. J Aerosol Med 17:289–298CrossRefGoogle Scholar
  12. Collings I, Watier Y, Giffard M et al (2010) Polymorphism of microcrystalline urate oxidase from Aspergillus flavus. Acta Crystallogr D Biol Crystallogr 66:539–548CrossRefGoogle Scholar
  13. Collins FS (1992) Cystic fibrosis: molecular biology and therapeutic implications. Science 256:774–779CrossRefGoogle Scholar
  14. Csoka AB, Scherer SW, Stern R (1999) Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31. Genomics 60:356–361CrossRefGoogle Scholar
  15. Davies J, Trindade MT, Wallis C et al (1997) Retrospective review of the effects of rhDNase in children with cystic fibrosis. Pediatr Pulmonol 23:243–248CrossRefGoogle Scholar
  16. Davydov L, Cheng JWM (2001) Tenecteplase: a review. Clin Ther 23:982–997CrossRefGoogle Scholar
  17. de Duve C (1996) The significance of lysosome in pathology and medicine. Proc Inst Med Chic 26:73–76Google Scholar
  18. Del Zoppo GJ, Saver JL, Jauch EC et al (2009) Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke 40:2945–2948CrossRefGoogle Scholar
  19. Dulik DM, Fenselaut C (1998) Use of immobilized enzymes in drug metabolism studies. FASEB J 2:2235–2240Google Scholar
  20. El Dib RP, Pastores GM (2010) Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev doi: 10.1002/14651858Google Scholar
  21. Fieker A, Philpott J, Armand M (2011) Enzyme replacement therapy for pancreatic insufficiency: present and future. Clin Exp Gastroenterol 4:55–73Google Scholar
  22. Fitzhugh DJ, Shan S, Dewhirst MW et al (2008) Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol 128:66–74CrossRefGoogle Scholar
  23. Germain DP (2002) Fabry disease: recent advances in enzyme replacement therapy. Expert Opin Investig Drugs 11:1467–1476CrossRefGoogle Scholar
  24. Giordano RC, Ribeiro MPA, Giordano RLC (2006) Kinetics of β-lactam antibiotics synthesis by penicillin G acylase (PGA) from the viewpoint of the industrial enzymatic reactor optimization. Biotechnol Adv 24(1):27–41CrossRefGoogle Scholar
  25. Graham ML (2003) Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev 55:1293–1302CrossRefGoogle Scholar
  26. Guce AI, Clark NE, Salgado EN et al (2010) Catalytic mechanism of human alpha-galactosidase. J Biol Chem 285:3625–3632CrossRefGoogle Scholar
  27. Gurbel PA, Hayes K, Bliden KP et al (2005) The platelet-related effects of tenecteplase versus alteplase versus reteplase. Blood Coagul Fibrinolysis 16:1–7CrossRefGoogle Scholar
  28. Hacke W, Kaste M, Bluhmki E et al (2008) Thrombolysis with alteplase 3–4.5 h after acute ischemic stroke. N Engl J Med 359:1317–1329CrossRefGoogle Scholar
  29. Harmatz P, Whitley CB, Waber L et al (2004) Enzyme replacement therapy in mucopolysaccharidosis type VI (Maroteaux–Lamy syndrome). J Pediatr 144:574–580CrossRefGoogle Scholar
  30. Hershfield MS, Buckley RH, Greenberg ML et al (1987) Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med 316:589–596CrossRefGoogle Scholar
  31. Hershfield MS, Chaffee S, Sorensen RU (1993) Enzyme replacement therapy with polyethylene glycol-adenosine deaminase in adenosine deaminase deficiency: overview and case reports of three patients, including two now receiving gene therapy. Pediatr Res 33:S42–S48Google Scholar
  32. Hershfield MS, Mitchell BS (1995) Immunodeficiency diseases caused by adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 7th edn. McGraw-Hill, New York, pp 1725–1768Google Scholar
  33. Hill JM, Roberts J, Loeb E et al (1967) l-Asparaginase therapy for leukemia and other malignant neoplasms, remission in human leukemia. J Am Med Assoc 202:882–888CrossRefGoogle Scholar
  34. Hilleman DE, Tsikouris JP, Seals AA et al (2007) Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. Pharmacotherapy 27:1558–1570CrossRefGoogle Scholar
  35. Ho DHW, Thetford BS, Carter CJK et al (1970) Clinical pharmacologic studies of l-asparaginase. Clin Pharmacol Ther 7:408–417Google Scholar
  36. Ho VQ, Wetzstein GA, Patterson SG et al (2006) Abbreviated rasburicase dosing for the prevention and treatment of hyperuricemia in adults at risk for tumor lysis syndrome. Support Cancer Ther 3:178–182CrossRefGoogle Scholar
  37. Hopwood JJ, Bate G, Kirkpatrick P (2006) Galsulfase. Nat Rev Drug Discov 5:101–102CrossRefGoogle Scholar
  38. Huisman G, Gray D (2002) Towards novel processes for the fine chemical and pharmaceutical industries. Curr Opin Biotechnol 13:352–358CrossRefGoogle Scholar
  39. Imming P, Sinning C, Meyer A (2006) Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov 5:821–834CrossRefGoogle Scholar
  40. Karnaukhova E, Ophir Y, Golding B (2006) Recombinant human alpha-1 proteinase inhibitor: towards therapeutic use. Amino Acids 30:317–332CrossRefGoogle Scholar
  41. Klein MD, Langer R (1986) Immobilized enzymes in clinical medicine: an emerging approach to new drug therapies. Trends Biotechnol 4:179–186CrossRefGoogle Scholar
  42. Kurochkina VB, Nys PS (1999) Enzymatic synthesis of beta-lactam antibiotics. I. Cefazolin. Antibiot Khimioter 44:12–16Google Scholar
  43. Lee KY, Kim DI, Kim SH et al (2004) Sequential combination of intravenous recombinant tissue plasminogen activator and intra-arterial urokinase in acute ischemic stroke. Am J Neuroradiol 25:1470–1475Google Scholar
  44. Longstaff C, Williams S, Thelwell C (2008) Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy. Cardiovasc Hematol Agents Med Chem 6:212–223CrossRefGoogle Scholar
  45. Maladkar NK (1994) Enzymatic production of cephalexin. Enzyme Microb Technol 16:715–718CrossRefGoogle Scholar
  46. Matasci M, David L, Hacker DL, Lucia Baldi L et al (2008) Recombinant therapeutic protein production in cultivated mammalian cells: current status and future prospects. Drug Discov Today Tech 5:37–42CrossRefGoogle Scholar
  47. McCredie KB, Ho DHW, Freireich EJ (2008) l-Asparaginase for the treatment of cancer. CA Cancer J Clin 23:220–227CrossRefGoogle Scholar
  48. McGirt LY, Vasagar K, Gober LM et al (2006) Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine. Arch Dermatol 142:1337–1342CrossRefGoogle Scholar
  49. Melov S, Ravenscroft J, Malik S et al (2000) Extension of life-span with superoxide dismutase/catalase mimetics. Science 289:1567–1569CrossRefGoogle Scholar
  50. Meneveau N, Schiele F, Vuillemenot A et al (1997) Streptokinase vs. alteplase in massive pulmonary embolism. A randomized trial assessing right heart haemodynamics and pulmonary vascular obstruction. Eur Heart J 18:1141–1148CrossRefGoogle Scholar
  51. Mundada L, Prorok M (2003) Structure–function analysis of streptokinase amino terminus. J Biol Chem 278:24421–24427CrossRefGoogle Scholar
  52. Nakamura M, Shirasawa E, Hikida M (1993) Characterization of esterases involved in the hydrolysis of dipivefrin hydrochloride. Ophthalmic Res 25:46–51CrossRefGoogle Scholar
  53. Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR et al (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 3421–3452Google Scholar
  54. Ohman EM, Van de Werf F, Antman EM et al (2005) Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial. Am Heart J 150:79–88CrossRefGoogle Scholar
  55. Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5:993–996CrossRefGoogle Scholar
  56. Ozcan C, Ergun O, Celik A et al (2002) Enzymatic debridement of burn wound with collagenase in children with partial-thickness burns. Burns 28:791–794CrossRefGoogle Scholar
  57. Pastores GM, Weinreb NJ, Aerts H et al (2004) Therapeutic goals in the treatment Gaucher disease. Semin Hematol 41:4–14CrossRefGoogle Scholar
  58. Pesu M, Candotti F, Husa M et al (2005) Jak3, severe combined immunodeficiency, and a new class of immunosuppressive drugs. Immunol Rev 203:127–142CrossRefGoogle Scholar
  59. Polmar SH, Wetzler EM, Stern RC et al (1975) Restoration of in-vitro lymphocyte responses with exogenous adenosine deaminase in a patient with severe combined immunodeficiency. Lancet 2:743–746CrossRefGoogle Scholar
  60. Ribeiro RC, Pui CH (2003) Recombinant urate oxidase for prevention of hyperuricemia and tumor lysis syndrome in lymphoid malignancies. Clin Lymphoma 3:225–232CrossRefGoogle Scholar
  61. RXList-Theinternet drug index (2013) http://www.rxlist.com/cgi/generic2/tenecteplase.html. Accessed 21 Jan 2013
  62. Saver JL (2004) Number needed to treat estimates incorporating effects over the entire range of clinical outcomes: novel derivation method and application to thrombolytic therapy for acute stroke. Arch Neurol 61:1066–1070CrossRefGoogle Scholar
  63. Schaefer RM, Tylki-Szymanska A, Hilz MJ (2009) Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs 69:2179–2205CrossRefGoogle Scholar
  64. Shah PL, Scott SF, Knight RA et al (1996) In vivo effects of recombinant human Dnase I on sputum in patients with cystic fibrosis. Thorax 51:119–125CrossRefGoogle Scholar
  65. Shak S, Capon DJ, Hellmiss R et al (1990) Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. PNAS 87:9188–9192CrossRefGoogle Scholar
  66. Sharma A, Jacob A, Tandon M et al (2010) Orphan drug: Development trends and strategies. J Pharm Bioallied Sci 2:290–299CrossRefGoogle Scholar
  67. Sikkens EC, Cahen DL, Kuipers EJ et al (2010) Pancreatic enzyme replacement therapy in chronic pancreatitis. Best Pract Res Clin Gastroenterol 24:337–347CrossRefGoogle Scholar
  68. Sikri N, Bardia A (2007) A history of streptokinase use in acute myocardial infarction. Tex Heart Inst J 34:318–327Google Scholar
  69. Singh RK, Mishra SK, Kumar N (2010) Optimization of α-amylase production on agriculture byproduct by Bacillus cereus MTCC 1305 using solid state fermentation. RJPBCS 1:867–876Google Scholar
  70. Stella VJ, Charman WN, Naringrekar VH (1985) Prodrugs. Do they have advantages in clinical practice? Drugs 29:455–473CrossRefGoogle Scholar
  71. Suri R, Metcalfe C, Lees B et al (2001) Comparison of hypertonic saline and alternate day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial. Lancet 358:1316–1321CrossRefGoogle Scholar
  72. Tremblay GM, Vachon E, Larouche C et al (2002) Inhibition of human neutrophil elastase-induced acute lung injury in hamsters by recombinant human pre-elafin (trappin-2). Chest 121:582–588CrossRefGoogle Scholar
  73. Tsurupa G, Medved L (2001) Identification and characterization of novel tPA- and plasminogen-binding sites within fibrinogen alpha C-domains. Biochemistry 40:801–808CrossRefGoogle Scholar
  74. Vellard M (2003) The enzyme as drug: application of enzymes as pharmaceuticals. Curr Opin Biotechnol 14:444–450CrossRefGoogle Scholar
  75. Veronese F, Calceti P, Schiavon O et al (2002) Polyethylene glycol-superoxide dismutase, a conjugate in search of exploitation. Adv Drug Deliv Rev 54:587–606CrossRefGoogle Scholar
  76. Weinreb NJ, Barranger JA, Charrow J et al (2005) Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. Am J Hematol 80:223–229CrossRefGoogle Scholar
  77. Wetzler M, Sanford BL, Kurtzberg J et al (2007) Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. Blood 109:4164–4167CrossRefGoogle Scholar
  78. White JT, Argento ML, Prince WS et al (2008) Comparison of neutralizing antibody assays for receptor binding and enzyme activity of the enzyme replacement therapeutic Naglazyme (galsulfase). AAPS J 10:439–449CrossRefGoogle Scholar
  79. Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393–1398CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of BiotechnologyIndian Institute of Technology GuwahatiGuwahatiIndia

Personalised recommendations