Transcript Nerve activates contraction

Chapter 6: Metabolism and
Enzymes
The chemistry of life is organized
into Metabolic Pathways
 The sum total of an organism’s chemical
reactions is called metabolism.
Metabolic Pathways are made of:
 Catabolic pathways release energy by
ATP
breaking
down complex molecules to
simpler compounds
Metabolic Pathways are made of:
 Anabolic pathways consume energy to
build complicated molecules from simpler
compounds.
ATP
Metabolic Pathways :
 Catabolic Pathways and Anabolic
Pathways act in tandem
Fig. 6.1 The inset shows the first two steps in the catabolic pathway that breaks down glucose.
 Chemical reactions can be classified as either
exergonic or endergonic based on energy.
 An exergonic reaction proceeds with a net
release of energy.
C6H12O6 + 6O2 -> 6CO2 + 6H2O
Fig. 6.6a
Free energy of
this reaction is
negative (G)
CATABOLIC
PATHWAY
 An endergonic reaction is one that absorbs
energy from its surroundings.
– Endergonic reactions store energy
6CO2 + 6H2O -> C6H12O6 + 6O2
ANABOLIC
PATHWAY
Free energy
of this
reaction is
positive
(G)
ATP: Adenine Triphosphate
 Exergonic Reactions and Endergonic Reactions
are Coupled using ATP
 ATP (adenosine triphosphate) is a type of
nucleotide
 ATP has the nitrogenous base adenine, the sugar
ribose, and a chain of 3 phosphate groups
ATP: Adenosine Triphosphate
 Bonds between PO4 groups can be broken
to release energy
 This is a hydrolysis reaction
ATP: High NRG PO4 Bond Transfer
 PO 4 released is
tagged to a
reactant
 Reactant is
phosphorylated
and now able to
undergo the
chemical reaction
 ATP can be
regenerated
 Energy Facts
Energy is used by the cell for: Mechanical Work
(movement), Transport (of macromolecules into
and out of cells), and Chemical Work (drive
endergonic reactions in anabolic pathways)
Plants transform light to chemical energy; they
do not produce energy.
 Activation energy: Energy needed by reactants to make
the products (NRG Barrier)
 Activation Energy is used to make transition state complexes
whose bonds are strained. Then, products form from these
transition state complxes by breaking and making new bonds.
 Activation energy: Enzymes lower the
Activation Energy needed for a reaction
 Enzymes drive most chemical reactions
in the body
 Activation energy: Enzymes lower the
Activation Energy needed for a reaction
 Enzymes drive most chemical reactions
in the body
Lactase (lactaid pills)
Lactose ----------------------------- > Glucose + Galactose
ENZYMES
Enzyme discovery to benefit homeland security
Enzymes are Proteins (names end in ase)
Enzymes:Are Substrate Specific
 Enzyme names have 2 parts:
 First part – which substrate it acts
on/what product is formed
 Second part – what it does
Malate Dehydrogenase
Citrate synthase
Enzymes:Are Substrate Specific
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1.
2.
3.
Oxidoreductases: Oxidation – reduction;
(dehydrogenase, reductase, oxidase)
Transferases: Transfer functional groups;
(transferase; phosphorylase)
Hydrolases: hydrolytic cleavage of
C-O, C-N, C-C bonds (phosphatase;
protease)
4.
5.
6.
Lyases – cleave bonds (decarboxylase)
Isomerases - geometric or structural changes
within a molecule (epimerase or isomerase)
Ligases - joining together of two molecules
using ATP (synthetase; ligase)
Enzymes: Active Site
Enzymes act on Substrates (reactants)
 Active Site: is a pocket or groove on the surface
of the enzyme into which the substrate fits
(often active siteis a nonpolar environment)
 Substrate binds to active site by hydrogen
bonding/weak forces to form an enzymesubstrate complex
Enzymes: Active Sites
 Active Site binding helps the reaction by:
•Substrates are placed in the correct orientation
for the reaction.
•Puts stress on bonds that must be broken, making
it easier to reach the transition state.
•R groups at the active site may create a conducive
microenvironment for a specific reaction.
•Enzymes may even bind covalently to substrates
in an intermediate step before returning to
normal.
Enzymes: How do they work?
 Induced Fit Model For Enzyme Action:
 Substrate binding to active site causes a
change in enzyme shape around active site
 The active site is molded into a tighter fit
around the substrates
 Substrates are held in close contact; EA is
lowered; products are formed and released
 Enzyme regains original shape; it is reused
A single molecule of enzyme can catalyze 1000’s of reactions per secon
Enzymes: How do they work?
 Enzymes can catalyze both forward and
backward reactions
 Direction of a reaction depends on
accumulation/removal of product
Malate Dehydrogenase
Enzymes: Factors affecting their
function (nine of them! - know these)
 Substrate Concentration
 Temperature
 pH
 Cofactors
 Coenzymes
 Competitive Inhibitors
 Non-competitiveInhibitor
 Allosteric Regulation and Co-operativity
 Feedback Inhibition
Enzymes: Factors affecting their function
The environment of the cell affects the
structure of enzymes (proteins) at the
secondary/tertiary/quarternary levels
The effect is perceived as a change in
reaction rate (rate of formation of product)
Enzymes: Factors affecting their function
1) Substrate Concentration
Low [S]: an increase in substrate speeds
binding to available active sites ([E] >>>> [S])
High [S]: Enzyme is SATURATED (all active
sites are occupied) (([S] >>>> [E])
At High [S]: To increase reaction rate, increase [E]
Enzymes: Factors affecting their function
2) Temperature
Low Temp: insufficient collisions between
active site and substrates
High Temp: Enzyme can denature and the
folding can unravel, damaging functionality
Optimal temp: Human enzymes – 37.5 oc
Enzymes: Factors affecting their function
3) pH – determines state of acidic/basic functional
‘R’ groups on amino acids, and hydrogen bonding
Low/High pH: changes the above interactions and
alters folding of enzyme protein/active site
Optimal pH: Human enzymes – pH 6-8
Enzymes: Factors affecting their function
4) Cofactors –inorganic helpers. Bind permanently or
reversibly to enzyme. What’s the biochemical reason?
• Examples: zinc, iron, and copper.
Photosystem I
multienzyme
complexes
Enzymes: Factors affecting their function
5) Coenzymes – organic helpers (same idea as
cofactors). Bind reversibly to enzymes - can
be re-used.
Examples:vitamins.
Enzymes: Factors affecting their function
 Inhibitors:
6) Competitive Inhibitors: Active Site Directed
Inhibitors - bind to active site and inhibit
binding of substrate
Enzymes: Factors affecting their function
 Inhibitors:
7) NonCompetitive Inhibitors: Bind to a
different site on enzyme called Allosteric
Site - diminishes bindng of substrate to
active site
Minimata Bay –
Japan (Mercury
Poisoning)
Nerve Gas Used on
Kurds by Iraq 1993
Enzymes: Factors affecting their function
8) Allosteric Regulation: Enzyme has several subunits hangs around in “active” or “inactive” state
 Effect of binding of regulator (inhibitor/activator) to one
subunit is translated to other subunits (cooperativity)
Enzymes: Factors affecting their function
9) Feedback Inhibition - a metabolic pathway is
turned off by its end product. End product becomes
a inhibitor for a very early step enzyme. Very
common!
Rate of a Reaction
 Reaction Rate- the change in the concentration of a
reactant or product with time. (M/s)
 General equation for a reaction:
– A→B
– Reactant → Product
 In order to monitor a reaction’s speed or rate,
we can look at one of two things:
– Decrease in [ reactant ]
– Increase in [ product ]
– Can be represented as:
rate = - Δ [A] / Δ t or
rate = Δ [B] / Δ t
Rate of a Reaction
Rate of a Reaction
Rate Calculations
 How do we calculate the rate of a reaction?
– We first need this information:
•
•
•
•
•
•
•
Time (s)
[reactant]
Or [product]
[ ] means concentration
Decrease in [reactant]/time OR
Increase in [product]/time
Calculate the slope of your graph - X axis - time; Y axis
- you choose
• (Y2-Y1)/(x2-x1)
Reaction rate calculation
Product Concentration (mM)
A ppearance of Glucose in an Enzyme
Catalysed Reaction with Lact aid Pills
Cont aining Lact ase
[Product] mM
45
40
35
30
25
20
15
10
5
0
0
10
30
60
Time in Seconds
120
180
Initial Stage of
Reaction:
[Substrate] is:
[Enzyme] is:
Number of Active Sites
available to catalyze this
reaction is:
Calculation of Initial
Reaction rate:
Ri =( y2-y1)/(x2-x1) =>
Rise/Run
Reaction rate calculation
Product Concentration (mM)
A ppearance of Glucose in an Enzyme
Catalysed Reaction with Lact aid Pills
Cont aining Lact ase
[Product] mM
45
40
35
30
25
20
15
10
5
0
0
10
30
60
Time in Seconds
120
180
Final Stage of
Reaction:
[Substrate] is:
[Enzyme] is:
Number of Active Sites
available to catalyze this
reaction is:
Calculation of Final
Reaction rate:
Rf =( y2-y1)/(x2-x1) =
Maximum Velocity:
Vmax