The Design of Metabolism
key concepts*
or How Biological Order
Comes About...
METABOLISM....
the catalytic reactions (run by enzymes) of cells.....
metabolic pathways [A --> B
--> C --> D
--> E]
- 2 Categories catalytic reactions -
-
CATABOLISM...
chemical oxidation of food
stuffs or
Cell Respiration
1) digestion of polymers (foods) [hydrolysis
reactions] to glucose
2) GLYCO-LYSIS glucose ---> pyruvate [splitting of sugar]
3) KREBS cycle
oxidation of Acetyl-CoA ---> CO2 +
NADH ----> H2O
-
4) ELECTRON TRANSFER ----> NADH + O2 ---->
H2O + H+ gradient
5) ATP SYNTHASE
---> use a H+ gradient to phosphorylate P + ADP
----> ATP
5 steps*
ANABOLISM...
Biosynthesis, often via...
coupled reactions - energetically unfavored w favored
reactions
1)
PHOTOSYNTHESIS reduction of CO2
to CH2O
-
-
-
ENERGY
- capacity or ability to do work
kinds: KINETIC - motion
POTENTIAL - stored energy; capacity to do work (eventually);
HEAT - assoc with movement of molecules in a body of matter;
most random form of energy (wasted).
Student Media Activities -
chapter 6A -
Energy Transformations |
 |
-
EXAMPLES
general: heat, light, sound, mechanical
of energy:
biological: synthetic, osmotic, mechanical,
-
-
molecules in
living cells have potential energy to do work...
- because of the arrangement (orientation) of their atoms
- in space... we call this chemical bond energy
&
-
the energy of cells is stored in the covalent bonds of their molecules.
HOMEOSTASIS ...most of cell's energy is needed to maintain
a steady state.
-
BIOENERGETICS
- is study of energy transformations (changes) in Biological systems is based on
EQUILIBRIUM THERMODYNAMICS...
-
1st LAW = Conservation of Energy (energy is a constant)
energy can not be created or destroyed, only transformed
... experimental caloric data says this LAW is true
► combustion of glucose releases 686
kilocalorie/mole of
heat
2nd LAW = Energy
transformations reduce the order of the universe
it's directional --- > toward
equilibrium (toward maximum disorder)
...
ENTROPY = amount of disorder in a system -
ENTROPY*
The Rules of Universe are simple :
Cities crumble,
stars go Supernova, & we're all
dying... (equilibrium...izing)
law
of ENTROPY
says... Degree of disorder of the Universe
-
(its randomness - its
entropy) CAN ONLY
INCREASE.
-
Cells obey Laws of
Chemistry & Physics
yet CELLS..... WOW ! .......become
more highly
ORDERED
as they grow...
fertilized egg ---> wing of bird, a spider's
web, the human eye,
dividing cells, etc...
from fertilized egg cell... which Feeds, Grows & Differentiates = HOW?
for part of a system to become more ordered - lose entropy
- (such as
a cell),
its surroundings must become more disordered
- gain entropy -
FOODs (light & covalent bond energy) |
 |
cell reactions give increased order within cell |
 |
with release of
HEAT |
HEAT (most
disordered form of energy) =
max entropy
ENERGY IN ----> CELL STRUCTURE
----> ENERGY OUT
How do we measure energy changes in cells...
-
Gibbs FREE ENERGY Equation
DG
= DH
- T
DS
free energy enthalpy
entropy
-
DG
is measures amount energy change in system that is able to do
Work...
-
DG
is a numerical
measure of how far a reaction is from equilibrium...
- Disorder
Increases (Entropy Increases)... when useful energy,
that
which could be used to do work, is dissipated as heat...
-
- cells are
ISOTHERMAL - (-2o to 37o) - thus DH =
0 above
Enthalpy
may be thought of as
heat content
of a system
-
cells function within a very narrow temp range
[23o-37oC],
and
thus DH is negligible
-
thus
DG can
PREDICT... the Direction of
Cellular Reactions...
TOWARD EQUILIBRIUM... toward Maximum ENTROPY
-
toward a release of free energy
-
-
-
-
-
-
-
CHEMICAL REACTON
A
<--->
B
Which Way is toward more Disorder?
DG = DG0’ +
RT
ln [p]/[r]
change in free energy content of a reaction...depends upon:
1. energy is stored in molecule's
covalent bonds
2. temperature is negligible... cells are
isothermal, i.e.,
DG
= actual free energy at any time in a reaction
DGo' = standard free energy [free
energy change under standard
conditions]
R = gas constant ( 2 x
10-3 Kc/mol)
T = absolute temp (-273oK)
ln = natural log
(conversion to log10 = 2.303)
3. at equilibrium
by definition
DG = 0
and we call [p]/[r]
= Keq
Free Energy Equation...
ΔG =
ΔG0'
+ RT ln [P]/[R]
@ equilibrium ΔG
= 0
0 =
ΔG0'
+ RT ln [P]/[R]
.... thus
rearranging
ΔG0'
= -RT ln [P]/[R]
@ equilibrium
[P] / [R]
= Keq
& @ 250C
... -RT
ln Keq = -(2.0)
(298) (2.303) lg10 Keq =
-[1372] lg10 Keq
thus..........
ΔG0'
= - [1372]
lg10 Keq
R = gas constant ( 2 x
10-3 Kc/mol)
T = absolute temp (-273oK)
ln = natural log
(conversion to log10 = 2.303)
The difference
between
ΔG
and
ΔG0'
ΔG0'
is a fixed value under
idealized conditions for a given reaction and
indicates in which direction
that reaction will proceed at standard conditions
standard
condition do not exist within a cell,
but ΔG0'
may be
used to predict the direction of a reaction
at a specific given time.
ΔG is
determined by the concentrations present
at a given time and
is a measure of how far a reaction is from
equilibrium then.
Cell metabolism is essentially a
non-equilibrium condition.
Metabolism works by changing the relative
concentrations of reactants
and products to favor the progress of non-favored
catalytic reactions.
when we solved above equation for DGo' we could see
relationship* of Keq to
DGo’
CHEMICAL
REACTIONS A <---->
B
Which Way &
Why?
EXERGONIC
REACTION - is one which releases free energy [
-
DG ]
Product (B) <<< energy
REACTANT (A) [energy stored in covalent bonds]
ex:
burning wood (cellulose)
glucose
polymer... potential energy.
breaks bonds, release heat & light ---> CO2 & H2O
fig 9.5*
cell respiration - cellular burning of glucose
molecules.
slower, multi-step process
that captures & releases
some energy... as
ATP
ENDERGONIC
REACTION - requires input of energy for
A --> B
Product (B) >>> energy than
REACTANT (A)
[ +
DG ]
ex:
photosynthesis (autotrophy)
glucose is made from CO2
+ H2O
--light-->
C6H12O6
energy
poor vs.
energy rich
CELL METABOLISM is
then a mix of...
Exergonic
& Endergonic reactions that occur inside of cells...
Concept Activities -
chapter 8.3 - Chemical
Reactions and ATP
How does Cell Metabolism really work
energetically?
for
RX's which share one or more intermediates (a
pathway)...
[ A-->B-->C-->D ]
the overall free energy
change (DG) is the
sum of
indiv DG's
DGo'
Glu + Fruc
---> Sucrose
+ 5.5 Kc/m
ATP ---> ADP + P
- 7.3 Kc/m
Glu +
ATP ---> G-1-P + Fruc ----> Suc + P
- 1.8Kc/m
COUPLED REACTIONS
- involves say... the linking of the hydrolysis of ATP
(a favored rx) to a thermodynamically
unfavored
reaction,
thereby
creating biological order (greater molecular structure).
another ex: synthesis of glutamine*
-
WHY
ATP ? ? ?
shouldn't any nucleotide work?
... the ENERGY MOLECULE of CELLS is
ATP
over the period of evolution, cells favored enzymes that
bound ATP & used its hydrolysis to drive endergonic reactions. |
 |
-
adenosine
triphosphate -
figure 6.8
* its
structure is its source of energy
Concept Activities - chapter 8.3 -
The Structure of ATP*
-
1. electrostatic repulsion
2. resonance
3. sphere of
hydration
| HYDROLYSIS
of ATP
ATP
DG0' = -7.3 Kc/m [ exergonic by some -7,300 cal/mol ] |
|
 |
How ATP
works -
phosphorylation*
& metabolic ATP coupling*
Concept Activities - chapter 8.3 -
Chemical Reactions & ATP.
next Lecture:
How cells make ATP*
 key concepts*
 the
material below is covered elsewhere under
proteomics &
enzymes
ENZYMES
& METABOLISM
What catalyzes the metabolic
reactions in cells..... ENZYMES
Enzyme (from Gk... meaning roughly) "in yeast" are proteins...
History of Biochemistry is tied to history of
enzymes
First described in
1850's in Pasteur's lab in Paris as "ferments"
and in 1926 Urease was
crystalized by James Sumner
Catalyze chemical reactions (A ---> B) in cells by breaking old
covalent bonds and forming new covalent bonds'.
Function as biological catalysts (but, differs from metal catalysts)
1. have complex,
specific structures (sequence of aa's)
2. act only upon a specific
substance (substrate)
3. do not change the
direction (energetics) of a reaction
only enhance rate of a chemical reaction A ---> B
without being used up in reaction
PROPERTIES
of ENZYMES
many require cofactor or coenzyme
cofactor - small
inorganic ion that catalyzes reaction
Cu+2 , Mg+2
, Mn+2, ,,etc...
coenzyme - smaller,
non-protein ligand
(9.4) which catalyzes rx
gains/loses e- ; transfers group ; breaks bond.
have an Active Site (6.12) - portion of enzyme protein that attaches the
substrate by means of weak chemical bonds
(H-bonds, ionic bonds, hydrophobic forces, etc...)
In chemical reaction
(6.9) enzymes function inertia
by lowering the Energy
of Activation (6.10) - Ea
by bringing reactants together
Reaction
path: E + S <---> ES <---> E + P
ENZYME-SUBSTRATE Complex:
enzymes are proteins with a specific 3-D
shape,
that binds substrate to its ACTIVE SITE
shape of enzyme is critical to its
ability to convert A ---> B
change enzyme's 3D shape - won't bind substrate
What will change shape of
a protein (denaturation) ?
1. temp -
increases kinetic motion, breaks H-bonds
2. pH -
changes charges = alters shape
3. inhibitors
- chemicals that bind to enzyme
& change its activity [competitive/non-competitive]
4. poisons -
organophosphorous compounds
(many insecticides) bind to enzymes of nervous system & kill
ENZYME
KINETICS
mathematical and/or graphical expression of the
reaction rates of enzymes ex: Catalase
2 H2O2 ---> 2 H2O
+ O2
 rate = ml of O2
per min a) 0.35 b) 0.6
c) 1.125
Some Characteristic Enzyme
Curves:
or how to determine if the reaction A —> B is enzymatic
1. |
Rate (0.8 ml O2/min) |
Vs. |
[E] |
| |
|
|
|
2. |
Rate (optimum) |
Vs. |
pH |
| |
|
|
|
3. |
Rate (optimum) |
Vs. |
Temperature |
| |
|
|
|
4. |
Rate (saturates) |
Vs. |
[S] |
Lenoir Michaelis - Maude Menten Enzyme Kinetics
A plot of rate
(amount of product per unit time) vs [S]
1. saturates.....
at [S] = Vmax (maximum velocity)
2. Km = substrate concentration at which rate is one-half
the maximal velocity (in above Km = 2 mg per min)
a measure of affinity of enzyme for its substrate
amount of [S] needed to reach
1/2 Vmax
Enzyme
Inhibition - a reduction in enzyme activity
Competitive (6.14).
binds to active site ...reversible
lower Km same
Vmax
Noncompetitive
binds to an allosteric site
same Km lower Vmax
Feedback inhibition
(6.16) - end product inhibits an initial enzyme
Enzyme
Cooperativity and Allosteric Regulation
enhancing enzyme activity by improving conformations
fig 6.15
and fig 6.17
The NAMING of ENZYMEs
4
digit Numbering System [1.2.3.4.]
1st Major Class of
Activity
2nd Subclass (type of bond acted upon)
3rd Subclass (group acted upon, cofactor required,
etc...)
4th Serial number ... sequence order
Six MAJOR CLASSES of Enzymes (Sigma Enzyme Index)
|
1. Oxidoreductases
[dehydrogenases] ....
catalyze oxidation reduction reactions, often w coe NAD+/FAD
Alcohol dehydrogenase
[EC 1.1.1.1]
ethanol + NAD+ -------> acetaldehyde + NADH |
|
|
2. Transferases
.... catalyze the transfer of functional groups
Hexokinase [EC
2.7.1.2]
D-glu + ATP ----------> D-glu-6-P + ADP |
|
3. Hydrolyases
.... catalyze hydrolytic reactions
add water across C-C bonds
Carboxypeptidase A
[EC 3.4.17.1]
[aa-aa]n + H2O
----> [aa-aa]n-1 + aa |
|
4. Lyases .... add
or remove groups to C= C bonds
Pyruvate decarboxylase
[EC 4.1.1.1]
PYR -----> acetaldehyde + CO2 |
|
5. Isomerases
[mutases] .... catalyze isomerizations
Maleate
isomerase [EC5.2.1.1.] (cis-trans isomerization)
maleate -----> fumarate |
|
|
6. Ligases ....
condensation of 2 substrates with splitting of ATP
Pyruvate carboxylase [EC 6.4.1.1.]
PYR + CO2 + ATP ------> OAA + ADP + P
|
-
Charles
Mallery,
-
Department of Biology,
-
University of Miami,
-
Coral Gables, FL 33124
Last Update -
06/03/2008
|
![[E]](http://fig.cox.miami.edu/~cmallery/150/metab/ratevse.jpg){kind=link}
