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Enzymes Compiled by : dr. Santoso
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
What Are Enzymes? ,[object Object],[object Object],[object Object]
Enzymes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
How do enzymes Work? Enzymes work by  weakening bonds  which  lowers activation energy
How  do  Enzymes Affect Reaction   Rates ? ,[object Object]
How  do  Enzymes Bind to   Substrates ,[object Object],[object Object],[object Object]
Enzyme-Substrate Complex The  substance  (reactant) an  enzyme  acts on is the  substrate Substrate Joins Enzyme
Active Site ,[object Object],Substrate Active Site Enzyme
Lock and Key Model Enzyme returns from the reaction unchanged and can now react with more   substrate.  enzyme S1 S2 S2 enzyme S1 ENZYME SUBSTRATE   COMPLEX enzyme SUBSTRATE MOLECULES Active site P P Products
Induced Fit ,[object Object],[object Object]
Induced Fit ,[object Object],[object Object],Enzyme Active Site substrate induced fit
Induced-Fit Model
Enzyme Cooperativity ,[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
Enzyme Kinetics ,[object Object]
Michaelis-Menten Equation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],V 0  = V max [S] / K M  + [S]
[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
What Affects Enzyme Activity? ,[object Object],[object Object],[object Object],[object Object]
1. Environmental Conditions ,[object Object],[object Object],[object Object],[object Object]
Temperature ,[object Object],Depending on the species, the  range of optimum activity is very broad.  Above is a comparison of human enzyme activity with that of bacteria found in hot springs and oceanic vents.
pH ,[object Object],[object Object],In the human body’s digestive tract there are variations in pH from area  to area.  The stomach’s juices’ pH is around 2 (acidic), the enzyme pepsin  found in the gastric juices has  optimum activity at a pH of 2.  The small intestine’s juice’s pH is around 8 (basic). The enzyme trypsin found in the small intestine’s juices has optimum activity at a pH of 8.
Substrate Concentration ,[object Object],Increasing Substrate Concentration Rate of Reaction Point of Saturation, all active sites are filled with substrate.
2. Cofactors and Coenzymes ,[object Object],[object Object],[object Object]
[object Object],[object Object]
Most water-soluble vitamins are components of coenzymes Vitamin Coenzyme Deficiency Thiamine (B 1 ) Thiamine pyrophosphate Beriberi (weight loss,other problems Riboflavin (B 2 ) FAD + Mouth lesions, dermatitis Nicotinic acid (niacine) NAD + Pellagra (dermatitis, depression) Pantohtinic acid Coenzyme A Hypertension  Biotin Biotin Rash, muscle pain
3. Enzyme Inhibitors ,[object Object],[object Object],[object Object],[object Object]
Competitive inhibitors chemicals that  resemble  an  enzyme’s normal substrate   and  compete  with it for the  active site . Substrate Enzyme Competitive inhibitor
Noncompetitive Inhibitors Inhibitors that  do not enter the   active site ,  but  bind to   another part   of the  enzyme   causing the  enzyme  to  change its shape , which in turn  alters the active site . Substrate Enzyme active site altered Noncompetitive Inhibitor
Competitive vs. Non-competitive inhibitors
[object Object],[object Object],[object Object],[object Object],[object Object]
Enzyme activity is regulated by four different mechanisms* ,[object Object],[object Object],[object Object],[object Object],[object Object]
Allosteric regulation of enzyme activity ,[object Object],[object Object]
Allosteric regulation Many allosterically controlled enzymse show quaternary structure
Covalent modification regulates the catalytic  activity of some enzymes ,[object Object]
Biotin ,[object Object]
Phosphorylation - an example of regulation by  reversible  covalent modification of the enzyme ,[object Object]
Top 5 reasons why phosphorylation is used to regulate enzyme activity: ,[object Object],[object Object],[object Object],[object Object],[object Object]
Summary:  Covalent modification ,[object Object],[object Object],[object Object]
[object Object]
[object Object],Proteolytic activation
Regulation of digestive enzymes
[object Object],[object Object],[object Object]
Pepsinogen is converted to pepsin by autocatalytic proteolysis at pH 2 ,[object Object]
Zymogen Pepsinogen Chymotrypsinogen Trypsinogen Procarboxypeptidase Proelastase Prothrombin Fibrinogen Factor VII Factor X Proinsulin Procollagen Procollagenase Active Enzyme Pepsin Chymotrypsin Trypsin Carboxypeptidase Elastase Thrombin Fibrin Factor VIIa Factor Xa Insulin Collagen Collagenase Function protein digestion protein digestion protein digestion protein digestion protein digestion blood clot formation blood clot formation blood clot formation blood clot formation plasma glucose homeostasis component of skin and bone remodeling processes during metamorphosis, etc.
[object Object],[object Object],[object Object]
Blood clot formation - an example of zymogen activations
[object Object],[object Object]
[object Object],[object Object],Proteolytic cleavage differs from phosphorylation
Stimulation and inhibition by control proteins ,[object Object]
Serpins - An example of inhibition by control proteins ,[object Object],[object Object],[object Object],[object Object],Trypsin (orange) bound to bovine pancreatic trypsin  inhibitor (violet).  His 57, Asp 102,  Gly 193, and Ser 195  in the active site of trypsin are shown  in green, red, cyan, and blue, respectively.  Lys 15 in BPTI forms a salt bridge with Asp 189 in trypsin in the trypsin:BPTI complex.  Binding of bovine pancreatic trypsin inhibitor is essentially irreversible .
Elastase is inhibited by  α 1-antitrypsin ,[object Object],[object Object]
[object Object],[object Object]
Summary of regulatory mechanisms ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Regulating the rates of enzyme-driven reactions ,[object Object],[object Object]
Enzyme 1 Enzyme 2 Enzyme 3 Inter- mediate Inter- mediate X Product Start of pathway Presence of product inhibits enzyme 1 Feedback inhibition Many enzymes are actually regulated by the end products of the reaction they catalyze This prevents too much product from being made
An example of  Feedback inhibition This example demonstrates how an end product can inhibit the first step in its production.  Isoleucine binds to the allosteric site of threonine deaminase and prevents threonine from binding to the active site because the shape of the active site is altered.  When the level of isoleucine drops in the cell’s cytoplasm, the isoleucine is removed from the allosteric site on the enzyme, the active site resumes the activated shape and the pathway is “cut back on” and isoleucine begins to be produced.
[object Object]

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Enzymes: Factors, Regulation, and Mechanisms

  • 1. Enzymes Compiled by : dr. Santoso
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  • 7. How do enzymes Work? Enzymes work by weakening bonds which lowers activation energy
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  • 11. Enzyme-Substrate Complex The substance (reactant) an enzyme acts on is the substrate Substrate Joins Enzyme
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  • 13. Lock and Key Model Enzyme returns from the reaction unchanged and can now react with more substrate. enzyme S1 S2 S2 enzyme S1 ENZYME SUBSTRATE COMPLEX enzyme SUBSTRATE MOLECULES Active site P P Products
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  • 30. Most water-soluble vitamins are components of coenzymes Vitamin Coenzyme Deficiency Thiamine (B 1 ) Thiamine pyrophosphate Beriberi (weight loss,other problems Riboflavin (B 2 ) FAD + Mouth lesions, dermatitis Nicotinic acid (niacine) NAD + Pellagra (dermatitis, depression) Pantohtinic acid Coenzyme A Hypertension Biotin Biotin Rash, muscle pain
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  • 32. Competitive inhibitors chemicals that resemble an enzyme’s normal substrate and compete with it for the active site . Substrate Enzyme Competitive inhibitor
  • 33. Noncompetitive Inhibitors Inhibitors that do not enter the active site , but bind to another part of the enzyme causing the enzyme to change its shape , which in turn alters the active site . Substrate Enzyme active site altered Noncompetitive Inhibitor
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  • 38. Allosteric regulation Many allosterically controlled enzymse show quaternary structure
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  • 49. Zymogen Pepsinogen Chymotrypsinogen Trypsinogen Procarboxypeptidase Proelastase Prothrombin Fibrinogen Factor VII Factor X Proinsulin Procollagen Procollagenase Active Enzyme Pepsin Chymotrypsin Trypsin Carboxypeptidase Elastase Thrombin Fibrin Factor VIIa Factor Xa Insulin Collagen Collagenase Function protein digestion protein digestion protein digestion protein digestion protein digestion blood clot formation blood clot formation blood clot formation blood clot formation plasma glucose homeostasis component of skin and bone remodeling processes during metamorphosis, etc.
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  • 51. Blood clot formation - an example of zymogen activations
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  • 60. Enzyme 1 Enzyme 2 Enzyme 3 Inter- mediate Inter- mediate X Product Start of pathway Presence of product inhibits enzyme 1 Feedback inhibition Many enzymes are actually regulated by the end products of the reaction they catalyze This prevents too much product from being made
  • 61. An example of Feedback inhibition This example demonstrates how an end product can inhibit the first step in its production. Isoleucine binds to the allosteric site of threonine deaminase and prevents threonine from binding to the active site because the shape of the active site is altered. When the level of isoleucine drops in the cell’s cytoplasm, the isoleucine is removed from the allosteric site on the enzyme, the active site resumes the activated shape and the pathway is “cut back on” and isoleucine begins to be produced.
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Notes de l'éditeur

  1. This example demonstrates how an end product can inhibit the first step in its production. Isoleucine binds to the allosteric site of threonine deaminase and prevents threonine from binding to the active site because the shape of the active site is altered. When the level of isoleucine drops in the cell’s cytoplasm, the isoleucine is removed from the allosteric site on the enzyme, the active site resumes the activated shape and the pathway is “cut back on” and isoleucine begins to be produced.