Download Biology Passage 2 - HCC Learning Web

Biological Chemistry and Metabolic Pathways
1. Reaction
a. Thermodynamics
b. Kinetics
2. Enzyme
a. Structure and Function
b. Regulation of Activity
c. Kinetics
d. Inhibition
3. Metabolic Pathways
a. REDOX Chemistry
b. Overview of Aerobic Respiration
c. Glycolysis
d. Pyruvate Catabolism and Krebs Cycle
e. Energy Harvesting
f. Fermentation
g. Energetics of Aerobic Respiration
h. Other Metabolic Pathways
Reaction
A. Thermodynamics (will reaction proceed? – yes or no)
1. (defined) – Study of the energetics of chemical reactions
2. First Law of Thermodynamics? Energy conserved
3. Second Law of Thermodynamics? Entropy increases
4. Gibbs Free Energy Change mathematically defines thermodynamics
G = H – TS (kcal/mol)
T = temperature
S = entropy
H = enthalpy = E - PV
(E = bond energy)
What variable represents Potential Energy? H
What variable represents Kinetic Energy? S
What value of G signifies reaction spontaneity? (-G)
kinetic energy > potential energy
5.
A+BC+D
a. G = (-); exergonic, energy given off
b. G = (+); endergonic, energy input necessary
1. Energy input into a closed system (i.e. test tube)? Heat
2. Energy input into a biological system (i.e. the body)? Coupling
A+BC+D
ATP  ADP + Pi
G = 7 kcal/mol
G = -12 kcal/mol
Gtotal = -5 kcal/mol
6. Summary
a. Thermodynamics measures reaction spontaneity: free energy difference between
reactants and products.
b. Free Energy Change (G) is additive, facilitating coupled reactions.
B. Kinetics (how fast will reaction proceed?)
1. (defined) – Study of the rate of chemical reactions
-Reactions proceed thru an unstable high energy transition state to form
a thermodynamically favorable product
-Energy required to produce the [TS] is the activation energy
-Activation energy can be lowered by a catalyst
-Body heat can supply activation energy in animals
2. Catalysts/Enzymes:
a. Stabilize the transition state of the reaction
b. Are not consumed
c. Do not effect free energy change (G)
Enzymes
A. Structure and Function
1. Most enzymes are globular proteins; spherical in shape
2. 4 Structural Elements
a. Primary: amino acid sequence - peptide/covalent/amide bonded
b. Secondary: -helix, -pleated sheet - hydrogen bonds
c. Tertiary: 3-dimensional folding - hydrophobic/hydrophilic interactions
d. Quarternary: polypeptide (subunit) interaction - disulfide bonds
3. Substrates are attracted to Enzymes through Recognition Pockets
a. recognition pockets can be covalently modified to attract the substrate
4. Catalysis occurs at the Active Sites
a. active site is close to recognition pocket (small molecule)
b. active site is far from recognition pocket (large molecule – protein)
B. Regulation of Activity
1. Covalent Modification - phosphorylation
2. Proteolytic Cleavage of regulatory sequence off polypeptide - zymogen
3. Dissociation of regulatory subunit from catalytic subunit of protein
4. Allosteric (Cooperative) Interaction
a. non-covalent process
b. regulatory molecule(s) bind away from the active site
c. interaction alters enzyme conformation
d. changes active site affinity (increase or decrease) for substrate
e. termed Tense (T) or Relaxed (R) state of protein relative to binding affinity
Feedback Inhibition: product D inhibits enzyme 1
C. Enzyme Kinetics
1. (defined): study of the rate of enzyme catalyzed product formation
2. Models assume constant enzyme concentrations
3. Vmax = maximum reaction rate – measures rate of catalysis for substrate
4. Km = substrate concentration at ½Vmax – measures affinity for substrate
5. Saturation Kinetics Model:
As you increase the substrate concentration, the reaction rate increases
at slower increments approaching until a plateau of rate, or Vmax. This
is due to saturation of enzyme active sites with the substrate.
6. Sigmoidal Kinetics Model:
In this model, the rate is influenced further by enzyme cooperativity.
Substrate binding at one site allosterically increases the affinity for substrates at
other sites due to conformational changes of the enzyme structure. T  R
D. Inhibitors (curve 1 has no inhibitor in the figure below)
1. Competitive Inhibitors (curve 3 in figure below)
a. bind at enzyme active site
b. directly competes with substrate binding
c. do not affect the Vmax; affect the Km
2. Non-Competitive Inhibitors (curve 2 in figure below)
a. bind at allosteric sites (away from the enzyme active site)
b. indirectly competes with substrate binding; changes active site conformation
c. affects the Vmax; no affect on Km
Can competitive inhibition be overcome by adding more substrate?
Yes, the substrate can quantitatively outcompete the inhibitor and bind the enzyme
at the active site.
Can non-competitive inhibition be overcome by adding more substrate?
No, the interaction between inhibitor and enzyme is away from the active site.
Metabolic Pathways
A. REDOX Chemistry
1. Chemoheterotrophs derive energy from external sources of carbon
This process is catabolic.
The opposite is? anabolic
2. Stoichiometry of Aerobic Respiration
C6H12O6 + 6O2 + 30ADP + 30P  6CO2 + 6H2O + 30ATP
a. Coupled REDOX reaction
What is the REDOX chemistry of glucose? Reduced glucose becomes
oxidized, generating reducing power and ultimately, metabolic energy.
b. Most metabolic energy (ATP) is derived from electrons (reducing power)
c. Electron Carriers shuttle and facilitate this conversion:
OX
RED
NAD → NADH
OX
RED
FAD → FADH2
d. Carriers are cofactors in respiration reactions and must be regenerated!
OX
RED
NAD ← NADH
OX
RED
FAD ← FADH2
B. Overview of Aerobic Respiraton
1. Glycolysis (Cytoplasm)
a. Split Glucose into 2 Pyruvate molecules; no oxygen necessary
2. Pyruvate Metabolism (Mitochondrial matrix)
a. Decarboxylate pyruvate producing acetate and CO2
b. no oxygen necessary but must be present for reaction to proceed
3. Kreb’s/TCA/Citric Acid Cycle (Mitochondrial matrix)
a. Oxaloacetate and acetate combine, forming citrate; OAA reforms in cycle
b. no oxygen necessary but must be present for cycle to proceed
4. Energy Harvesting (Mitochondrial inner membrane)
a. Metabolic energy generated from reduced electron carriers
b. Carriers must be recycled
c. Oxyen necessary as terminal electron acceptor
C. Glycolysis
D. Pyruvate Catabolism and Kreb’s Cycle
E. Energy Harvesting
F. Fermentation
G. Energetics of Aerobic Respiration (glucose catabolism)
H. Other Metabolic Pathways
1. Glycogenolysis – glycogen breakdown forming glucose
2. Gluconeogenesis – de novo synthesis of glucose from many sources
3. -Oxidation – de novo generation of acetyl-CoA and pyruvate from fat
4. Amino acid catabolism – removal of amino group from amino acid