1. Enzymes

2. Enzymes
Large bio-molecules that increase the rate of reaction in living systems
Enzymes act as catalyst – molecules that speed up a chemical reaction by lowering the activation energy

3. Enzymes Most Enzymes are globular protein molecules
Other types such as ribozymes are common
Extremely effective causing reactions to be 109 to 1020 times faster
Extremely specific - each reaction catalyzed by only 1 enzyme
e.g. Trypsin: cleaves peptide linkages only on carboxyl side of lysine and arginine
Many enzymes are stereospecific: Arginase converts L-arginine to to L-ornithine but does not convert D-arginine

4. Enzymes There are more than 3000 enzyme in a cell
Enzymes are distributed in the body relative to their need (digestive enzymes in stomach and pancreas)
From Yahoo Images

5. Enzyme Nomenclature
Enzymes are typically given names based on the reactions they are involved in with most ending in …… ase
Lactate dehydrogenase
speeds up removal of H from lactate
Acid phosphatase
cleaves phosphate ester bonds under acidic conditions
(some older ones do not end in “ase” like pepsin, trypsin, chymotrypsin)

6. Enzymes are classified into six major groups according to their reactions
1. Oxidoreductases
catalyze oxidations and reductions
2. Transferases
catalyze NH2, CH3, etc. from one molecule to another
3. Hydrolases
catalyze hydrolysis reactions
4. Lyases
catalyze addition of two group to make C=C or removes two atoms to create C=C
5. Isomerases
catalyze isomerization reactions
6. Ligases or Synthetases
catalyze joining of two molecules

7. Enzyme - Youtube

8. Enzyme Terms Most enzymes are made of just a Polypeptide chain
Some enzymes have a nonprotein portion called a cofactor
The protein portion is called an apoenzyme
Cofactors = nonprotein portions = coenzyme
Metal Cofactors such as Zn2+, Mg2+
an apoenzyme cannot catalyze a reaction withouth its cofactor

9. Enzyme Terms Substrate = compound on which the enzyme “works”
Active site = specific portion of the enzyme
where substrate binds

11. Enzyme Terms Activation = process that makes an
inactive enzyme active
Inhibition = any process that makes an enzyme
less active or inactive
competitive vs. noncompetitive inhibition

12. Enzyme Activity Enzyme and substrate concentration
Enzyme concentration

13. Enzyme Activity Enzyme and substrate concentration
maximum rate (enzyme saturation)

14. Enzyme Activity Temperature – changes conformation rate Temperature
37o C
Temperature

15. Temp Effect - youtube

16. Enzyme Activity pH – changes conformation or denatures rate acidic pH
5.3 pH
basic

17. Denaturation - pH

18. Mechanism Mechanism of Enzyme Activity Highly specific
Enzyme-Substrate Complex
Lock and Key Model
rigid 3-D structure
fits exactly into active site
active site may have only 1 or 2 AA, enzyme may have hundreds!

19. Mechanism Mechanism of Enzyme Activity Induced Fit Model
Daniel Koshland
some flexibility
shape changes to fit substrate
hand and glove analogy

20. Inhibitors Competitive Inhibition
Something that inhibits the enzymes ability to react
Competitive Inhibition
Inhibitor molecule takes the active site
Substrate cannot react at active site
Large concentrations of substrate “overcome” inhibition (competitive)

21. Inhibitors Noncompetitive Inhibition
Something that inhibits the enzymes ability to react
Noncompetitive Inhibition
Inhibitor molecule takes other than the active site
Enzyme structure is changed - active site is altered
Large concentrations of substrate do NOT change inhibition (noncompetitive)

22. Inhibitors Inhibition Substrate concentration No inhibitor
Competitive Inhibitor
Noncompetitive Inhibitor

23. Enzyme inhibition - youtube

25. Chemical Connections page 592

26. Enzyme Regulation A B C D Feedback Control
Regulation by environmental control
One enzyme may control the activity of another! A B C D E1 E2 E3
Product D may inhibit E1

27. Enzyme Regulation Proenzymes
Enzymes manufactured may need a small polypeptide removed to become active
Also called zymogens
Example:
trypsin is synthesized as trypsinogen
trypsinogen is the inactive form
once in the digestive tract it is converted to trypsin

28. Enzyme Regulation Allosterism
regulation at site other than active site
regulatory site
active site changes and becomes more or less reactive
positive modulation
negative modulation
“regulator”
“Thus the allosteric enzyme is controlled by the regulator.”

29. Enzyme Regulation Isoenzymes
Same enzyme, but different form, in different tissues:
Lactate dehydrogenase (4 subunits) made from two different types – H and M
H4 predominates in heart
M4 predominates in liver and skeletal muscle

30. Medical Diagnosis AST aspartate aminotransferase
Most enzymes are confined to cells
Small amount can be found in blood, urine, etc.
Analysis of body fluids can help diagnose disease or injury (enzymes spilled to serum)
E.g. Heart Attack (???) --- check serum levels:
AST aspartate aminotransferase
LD-P lactate dehydrogenase
CK creatine kinase

31. Medical Diagnosis Enzyme Normal Fluid Disease
alanine aminotransferase (ALT) 3-17 U/L serum Hepatitis
acid phosphatase serum Prostate cancer
alkaline phosphatase (ALP) serum Liver/bone disease
amylase serum Pancreatic disease or mumps
aspartate aminotransferase (AST) serum Heart attack or hepatitis
7-49 CSF
lactate dehydrogenase (LD-P) serum Heart attack
creatine kinase (CK) serum Heart attack
phosphohexose isomerase (PHI) serum Heart attack