Download Bio1A Unit 1-5 Metabolism Notes File

Metabolism
Metabolic Pathway: series of steps from reactants to products, usually enzyme catlyzed
Enzyme 1
A
Reaction 1
Starting
molecule
Enzyme 2
B
Reaction 2
Enzyme 3
C
Reaction 3
D
Product
Catabolic pathways - release energy by breaking down (degredation) complex molecules into
simpler compounds
• Cellular respiration: breakdown of glucose  Energy
Anabolic pathways - consume energy to build complex (synthesis) molecules from simpler ones
• The synthesis of protein from amino acids is an example of anabolism
Thermodynamics - study of energy transformations
Energy
• the capacity to cause change (WORK)
• exists in various forms
• Energy can be converted from one form to another
Kinetic energy is energy associated with motion
Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules
Potential energy is energy that matter possesses because of its location or structure
–
Gravity, electrical (charge)
Chemical energy is potential energy available for release in a chemical reaction (in bonds)
Measured in terms of work
1 calorie (cal)= 4.2 joules = energy to raise 1 g water 1°C
1 Calorie (Cal or kcal)
Exergonic reaction proceeds with
a net release of free energy
spontaneous
Endergonic reaction absorbs free
energy from its
surroundings  not
spontaneous
first law of thermodynamics, the energy of the universe is constant:
• Energy can be transferred and transformed, but it cannot be
created or destroyed
• The first law is also called the principle of conservation of
energy
Second law of thermodynamics, the energy of the universe is constant:
•During every energy transfer / transformation, some energy is
unusable (often lost as heat)
•Every energy transfer or transformation increases the entropy
(= disorder) of the universe
change in free energy (∆G)
Measurement of the energy change from reactants
to products for a particular reaction
∆G°
naught
Standard conditions
T = 25°C
P = 1 atm
[C]=1 M, all reactants
Water 55.6M
H+ conc = 10-7M (pH=7.0)
2nd Law  Only processes with a negative ∆G are spontaneous / can occur
• Spontaneous processes can be harnessed to perform work
Equilibrium and Metabolism
•
Reactions in a closed system eventually reach equilibrium and then do no work
•
Cells are not in equilibrium; cells are open systems experiencing a constant flow of materials
•
A defining feature of life is that metabolism is never at equilibrium
•
A catabolic pathway in a cell releases free energy in a series of reactions
Closed system
Open system
coupling exergonic reactions to endergonic reactions
•Most energy coupling in cells is mediated by ATP
•Overall, the coupled reactions are exergonic
ATP  ADP + Pi + Energy is exergonic
ΔG° = - 7.3kcal/mol
Enzymes
• An enzyme is a catalytic protein
• A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction
• speed up metabolic reactions by lowering energy barriers
How do enzymes work?
• substrate binds to the active site of the enzyme
• The active site can lower an EA barrier by
– Orienting substrates
– Straining substrate bonds
– Providing a favorable microenvironment
– Covalently bonding to the substrate
Induced Fit Model
• Substrate causes a change in shape of enzyme new
• shape brings groups in active site into positions that
enhance their ability to catalyze the reaction
• More accepted model
High efficiency
substrate binds to the active site of the enzyme
• Limited area of overall enzyme
• Typically Transient – weak bonds involved
• Substrate must bind and leave quickly otherwise occupies the enzyme
Enzyme Kinetics
• An enzyme’s activity can be affected by
– General environmental factors, such as
temperature and pH, concentrations
– Chemicals that specifically influence the
enzyme
• Each enzyme has an optimal temperature in which it
can function
• Each enzyme has an optimal pH in which it can
function
Michealis-Menten Kinetics
Behavior of many Enzymes
Enzyme rate vs Substrate Concentration
Vmax = Max Rate
Michealis-Menten Constant
Km = substrate concentration
for 50% Rate
Reflects speed of enzyme binding
Artificially generated in test tube
Information gives insight into enzyme
•Km too high  is this accurate for the cell?
Ex: Km = 100mM but cell only has 1mM
Need something to activate & change Km (ex: temp)
•Vmax too low  something is missing
Enzyme requirements – Cofactors
•Low MW compounds at active site
Terms are not strictly held – usage not fixed
Cofactors - nonprotein enzyme helpers
- inorganic (such as a metal in ionic form) or organic
- Cofactors usually refers to inorganic
• Coenzyme - loosely bound organic cofactor
- Name stresses affect on enzyme
- include vitamins
• Prosthetic Group = covalently bound organic cofactor
- Name stresses the fact that it is tightly bound
- Function is partially to affect enzyme shape and partially for interacting with substrates
Enzyme Inhibitors / Activators
• Competitive inhibitors bind to the active site of an enzyme, competing with the substrate
• Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to
change shape and making the active site less effective
 Allosteric Affect
• Examples of inhibitors include toxins, poisons, pesticides, and antibiotics
• Activators bind to another part of an enzyme, causing the enzyme to change shape and
making the active site more effective
- Allosteric regulation may either inhibit or stimulate an enzyme’s activity
- Allosteric regulation occurs when a regulatory molecule binds to a protein at one site
(away from active site) and affects the protein’s function at another site (active site)
Cooperativity
• form of allosteric regulation  amplifies enzyme activity
• binding of substrate to one active site stabilizes favorable conformational
changes at all other subunits
Substrate = activator
S-Curve
Post-Translational Modifications
Can affect enzyme activity
Example:
Proteolysis = protein cleavage (by proteases)
Ex: Zymogens = inactive precursor
Inactive
protease
active
Phosphorylation - adding phosphate
• addition or removal can activate or repress
• Kinases (generally to add Pi)
• Phosphatases (generally to remove Pi)
•Reversible & Instantaneous
• added to Serine, Threonine, or Tyrosine
- All have alcohol group (-OH)