1. Ch 4: Energy and Cellular Metabolism
Energy as it relates to Biology
Chemical reactions
Enzymes and how they speed rxs
Metabolism and metabolic pathways
Catabolism (ATP production)
Anabolism (Synthesis of biologically important molecules)

2. Energy in Biological Systems
Review on your own!

3. Chemical Reactions Transfer energy or use energy to do work
Substrates / reactants
Products
A + B C + D
Bioenergetics: Study of energy flow through biol. systems
Reaction rate = speed of reaction

4. Activation Energy Starts Reaction
Fig 4-3
Reversible (most biol. rxs.) vs. irreversible reactions

5. Endergonic vs. Exergonic Reactions
Coupling endergonic and exergoinic rxs
Direct coupling vs. indirect coupling
Which kind?

6. Enzymes are Proteins acting as Biological Catalysts
4 important characteristics of enzymes
 chemical reaction rate by lowering activation energy
are not changed themselves
do not change nature of rx nor result
are specific
Fig 4-8

7. Active Site:
Small region of the complex 3D structure is active (or binding) site.
Enzymes bind to substrate
Troponin I and T are structural components of cardiac muscle. They are released into the bloodstream with myocardial injury. They are highly specific for myocardial injury--more so than CK-MB--and help to exclude elevations of CK with skeletal muscle trauma. Troponins will begin to increase following MI within 3 to 12 hours, about the same time frame as CK-MB. However, the rate of rise for early infarction may not be as dramatic as for CK-MB.
Troponins will remain elevated longer than CK--up to 5 to 9 days for troponin I and up to 2 weeks for troponin T. This makes troponins a superior marker for diagnosing myocardial infarction in the recent past--better than lactate dehydrogenase (LDH). However, this continued elevation has the disadvantage of making it more difficult to diagnose reinfarction or
Old: Lock-and-key model / New: Induced-fit model
Fig 2-16

8. Naming of Enzymes mostly suffix -ase first part gives info on function
Not in book
Naming of Enzymes
mostly suffix -ase
first part gives info on function
Kinase
Phosphatase
Peptidase
Dehydrogenase
examples

9. Isozymes = different models of same enzyme (differ in 1 or few aa)
Catalize same reaction under different conditions and in different tissues/organs
Examples:
Amylase
LDH → importance in diagnostics
(LDH) Lactate dehydrogenase  - Total LDH will begin to rise 2 to 5 days after an MI; the elevation can last 10 days.
U/L
Normal Adult Range: U/L Optimal Adult Reading: 125
Review Table 4-3

10. Enzyme Activity depends on
proteolytic activation (for some)
cofactors & coenzymes (for some)
temperature pH
other molecules interacting with enzyme

11. 1) Proteolytic Activation
Also
Pepsinogen Pepsin
Trypsinogen Trypsin

12. 2) Cofactors & Coenzymes
structure:
___________ molecules (e.g. ?)
function:
conformational change of active site
structure:
Organic molecules (vitamin
derivatives, FADH2 ....)
function:
act as receptors & carriers
for atoms or functional
groups that are removed
from substrate

13. 6) Molecules interacting with enzyme cont.
Competitive inhibitors:
reversible binding to active site
Fig 2-19
block active site
Also possible: irreversible binding via covalent bonds, e.g.:
Penicillin
Tamoxifen

14. Reversible Reactions follow the Law of Mass Action
Fig 4-9

15. Three Major Types of Enzymatic Reactions:
Oxydation - Reduction reactions
(transfer of ?)
Hydrolysis - Dehydration reactions
(breakdown & synthesis of ?)
Addition-Subtraction-Exchange reactions

16. Metabolism Anabolism Catabolism   Catabolism (ATP production)
Anabolism (Synthetic pathways)
Anabolism
Catabolism  

17. Metabolic pathways = network of linked reactions
Metabolism definition: ___________
Metabolic pathways = network of linked reactions
Cells regulate metabolic pathways via
Control of enzyme concentration
Modulator production (allosteric modulators, feedback inhibition, Fig 4-11)
Different enzymes for reversible rxs, Fig 4-12)
Compartmentation of enzymes
ATP / ADP ratio

18. Catabolic Pathways: ATP-Production
Amount of ATP produced reflects on usefulness of metabolic pathways:
Aerobic pathways
Anaerobic pathways
Different biomolecules enter pathway at different points

19. Glycolysis From 1 glucose to 2 pyruvate molecules
Main catabolic pathway of cytoplasm
Does not require O2  part of _________ and ____________ catabolism
Starts with phosphorylation (“Before doubling your money you first have to invest!”)
Fig 4-13

20. Pyruvate has 2 Possible Fates
Anaerobic catabolism: Pyruvate
lactate
Aerobic catabolism: Pyruvate
Citric Acid Cycle

21. Citric Acid Cycle Other names ? Takes place in ? Energy Produced:
1 ATP
3 NADH
1 FADH2
Waste – 2 CO2
Fig. 4-16

22. Final step: Electron Transport System
Chemiosmotic theory / oxydative phosphorylation
Transfers energy from NADH and FADH2 to ATP (via e- donation and H+ transport)
Mechanism: Energy released by movement of e- trough transport system is stored temporarily in H+ gradient
NADH produces a maximum of 2.5 ATP FADH2 produces a maximum of 1.5 ATP
1 ATP formed per 3H+ shuttled through ATP Synthase
Fig 4-17

23. Cellular Respiration
Maximum potential yield for aerobic glucose metabolism: ATP synthesized from ADP
H2O is a byproduct

24. Synthetic Pathways Anabolic rxs synthesize large biomolecules
Unit molecules Macromolecules
nutrients &
energy required
Polysaccharides
Lipids
DNA
Protein

25. Glycogen Synthesis Gluconeogenesis Made from glucose
Stored in all cells but especially in
Liver (keeps 4h glycogen reserve for between meals)
Skeletal Muscle  muscle contraction
Gluconeogenesis
Glycolysis in reverse
From glycerol, aa and lactate
All cells can make G-6-P, only liver and Kidney can make glucose

26. Protein Synthesis
Proteins are the key to cell function → necessary for all cell functions
Protein synthesis is under nuclear direction  DNA specifies Proteins
DNA mRNA Protein ? ?

27. How can only 4 bases in DNA encode > 20 different aa in protein?
1 letter word: 1 base = 1 aa  how many possibilities?
2 letter word: 2 bases = 1 aa how many possibilities?
3 letter word: 3 bases = 1 aa  how many possibilities?
3 letter words = base triplets or codons

28. Redundancy of Genetic Code
1 start codon (AUG = Met)
3 stop codons
60 other codons for 19 aa

29. Transcription DNA is transcribed into complementary mRNA by
RNA Polymerase
+ nucleotides
+ Mg2+ ( = ?)
+ ?
Gene = elementary
unit of inheritance
Compare to Fig. 4-25

30. Translation mRNA is translated into string of aa (= polypeptide)
2 important components ??
mRNA + ribosomes + tRNA meet in cytoplasm
Anticodon pairs with mRNA
codon  aa determined
Amino acids are linked via
______________ bond.
Fig 4-27

31. Protein Sorting Due to signal/targeting sequence
Post – Translational protein modifications: Folding, cleavage, additions  glyco- , lipo- proteins
Protein Sorting
Due to signal/targeting sequence
No targeting sequence  protein stays in cytoplasm
Targeting sequence  protein destined for translocation into organelles or for export from cell

32. Transition vesicles to
For “export proteins”: Signal sequence leads growing polypeptide chain across ER membrane into ER lumen
Modifications in ER
Transition vesicles to
Golgi apparatus for further modifications
Transport vesicles to cell membrane
Compare to Fig 4-28

33. DNA Replication
Semi- conservative
DNA polymerase

34. the end
Running problem: Tay-Sachs Disease