Transcript Ch 12-Metabolism Overview Introduction to Metabolism • A principle task of Biochemistry is to understand how cells regulate its assorted reaction sequences and.

Ch 12-Metabolism Overview
Introduction to Metabolism
• A principle task of Biochemistry is to
understand how cells regulate its assorted
reaction sequences and controls its internal
environment
• Previously, we have looked at this from an
individual compound perspective
• Now we switch to reaction sequences, called
pathways, the relationship between each
pathway and cellular architecture, the
biological importance of each pathway,
control mechanisms that regulate flux, and
experimental methods used to investigate
metabolism
• Flux- intracellular reaction rates
Metabolism Overview
•Metabolism is divided into
two categories:
•Catabolism- processes
related to the degradation
of complex substances
•Anabolism- processes that
synthesize complex organic
molecules
• There are 3 stages associated
with both:
•Stage 1- the interconversion
of macromolecules with their
monomer parts
•Stage 2- The interconversion
of the monomers with their
simpler parts
•Stage 3- The ultimate
degradation to or synthesis
from inorganic compounds
such as CO2, H2O, NH3
Basic Terms
• Intermediary Metabolism- all reactions concerned
with storing and generating metabolic energy and
with using that energy in biosynthesis of low
molecular weight compounds and energy storage
compounds
• These reactions do not include those that need a
nucleic acid template.
• The information needed is already embedded in the
structure of the enzyme that catalyzes the reaction.
Basic Terms
• Energy Metabolism- a part of intermediary
metabolism consisting of pathways that store
or generate metabolic energy
• Central pathways- pathways that are
substantially the same in many different
organisms, and they account for relatively
large amounts of mass transfer and energy
generation within a cell.
Synthesis vs. Consume
• Most organisms derive both the raw materials
and the energy for biosynthesis from organic
fuel molecules such as glucose
• The central pathways revolve around the
oxidation of fuel molecules and the synthesis
of small biomolecules from the resulting
fragments
• This is true for all aerobic organisms
Synthesis vs. Consume
• The basic distinction of these organisms lies in
the source of their fuel molecules
• Autotrophs- synthesize glucose and all other
organic compounds from inorganic Carbon,
mainly CO2
• Heterotrophs- can synthesize their organic
metabolites only from other organic
compounds, which they must comsume.
•This figure presents
metabolism in much
more detail than the
previous image and is
the basic road map for
metabolism
•The middle of the
figure, with the larger
arrows, are the central
pathways of energy
metabolism
•Glycolysis- a stage 2 pathway
for degradation of
carbohydrates in both aerobic
and anaerobic cells.
•The major input to glycolysis is
glucose.
•It usually comes from energy
storage polysaccharides or
dietary carbohydrates
•Notice that as glucose is
converted to pyruvate, a 3
carbon keto acid, an ADP is
converted to an ATP!!
• Anaerobic organisms further reduce pyruvate
to simpler compounds such as ethanol and
CO2, through a process called fermentation
• In aerobic organisms, the major fate of
pyruvate is acetyl-coenzyme A, acetyl-CoA,
which is then incorporated into the Citric Acid
Cycle (CAC)
The Citric Acid Cycle
• The CAC is the principle stage 3 pathway in aerobic
organisms.
• This cycle accepts simple carbon compounds from
carbohydrates, proteins, and lipid degradation and
oxidizes them to CO2
• All catabolic pathways converge at the CAC
• The oxidation reactions of the CAC generate
reduced electron carries (NADH, FADH2) whose
reoxidation drives ATP biosynthesis, primarily
through processes in the mitochondrial respiration
chain.
• Other stage 2 pathways also deliver AcetylCoA to the CAC
– Ex. b-oxidation of fatty acids and the amino acid
oxidation pathways
• The 2 carbons of Acetyl-CoA don’t have to be
oxidized by the CAC
• They can also be used as building blocks for
anabolic pathways to produce fatty acids,
steriods, and amino acids
• These and other biosynthesis processes use a
reduced electron carrier, NADPH, which is
structurally very similar to NADH.
Distinct Pathways for Biosynthesis and
Degradation
• From the earlier figures, it may appear that most
catabolic pathways operate simply as the reversal of
the analogous anabolic pathways and/or vice versa.
• However, the opposed pathways are quite distinct
from one another
• They may share common intermediates, but they
are separate reactions sequences, regulated by
distinct mechanisms, and use different enzymes
• Some even occur in different locations!
Example
• Fatty acid synthesis takes place in the cytosol
while fatty acid degradation through oxidation
takes place in the mitochondria.
• The biosynthesis and degradation pathways
are rarely, if ever, simple reversals of one
another!
Reasons for separate pathways
• The existence of separate pathways is
important for 2 reasons:
1) Thermodynamics-Recall that for a pathway to proceed in a
given direction, it must be exergonic, in that
direction
-if it is strongly exergonic, than the reverse
direction would be just as strongly
endergonic!!
Reasons for separate pathways
2) Control- Using separate pathways for
biosynthesis and degradation processes is crucial
for control, so conditions that activate one
pathway tend to inhibit the opposed pathway.
Example:
ATP levels Low:
ATP levels High:
-less carbon is oxidized in CAC -more carbon is oxidized in
CAC
-Carbon stored as fats and
-Fatty acid and carbohydrate
carbs so fatty acid syn. and
breakdown are
Gluconeogenesis are activated
activated
Futile Cycle
• Futile Cycle- a cycle in which no net work is
done.
• Separation is important to avoid a futile cycle:
Occasional Exceptions
• Occasionally, opposing processes occur in the
same location but are controlled by opposing
methods.
• One example occurs in carbohydrate
metabolism.
– #1 occurs in glycolysis
– #2 occurs in gluconeogenesis
– Both occur in the cytosol!!
Substrate Cycle
• However, enzymes catalyzing both reactions
respond to allosteric effectors, such that one
enzyme is inhibited by conditions that activate
the other.
• This effective control prevents the futile cycle
and are referred to as a Substrate Cycle.
• Substrate Cycle- two seemingly opposed
cellular reactions that are independently
controlled.
Substrate Cycles
• Substrate cycles represent an efficient
regulatory mechanism, because a small
change in the activity of either or both
enzymes can have a much larger effect on the
flux of metabolites.
Bioenergetic Considerations
• Recall that thermodynamically unfavorable,
endergonic reactions will proceed smoothly in
the unfavored direction only if it can be
coupled to a thermodynamically favorable,
exergonic reaction.
• In living systems, most of the energy needed
to drive biosynthetic reactions is derived from
the oxidation of organic substrates
• Oxygen, the ultimate electron acceptor for
aerobic organisms, is a strong oxidant; it has a
marked tendency to attract electrons and
becomes reduced in the process
• The energy released is constant whether we
burn wood, which is the oxidation of a glucose
polymer (cellulose); combust glucose in a
calorimeter, or the metabolic oxidation of
glucose
• The difference is how the energy is released.
• When wood is burned, most energy is
released as heat with the only useful work
being done by a secondary system.
• In biological oxidations, the reactions occur
without a large increase in temperature and
some of the free energy is captured as
chemical energy
• This chemical energy is captured largely
through the synthesis of ATP
• The hydrolysis of ATP can then be coupled to
many processes to provide this chemical
energy for biological work
• In the catabolism of glucose, about 40% of the
released energy is used to drive
ADP + Pi → ATP
• Most biological oxidations do not involve
direct transfers of electrons from a reduced
substrate to oxygen
• A series of coupled oxidation-reduction
reactions occur with the electrons passed to
intermediate electron carriers such as NAD+
and then to oxygen
• This reaction sequence is called the electron
transport chain, or respiratory chain and
oxygen is called the terminal electron
acceptor
• The potential energy in organic substrates is
released in small increments, which makes it
easier to control oxidations, more efficient,
and easier to capture the energy released.
Make Sure To Read:
• Energy Yields, Respiration Quotients, and
Reducing Equivalents
• ATP as a Free Energy Currency
• Thermodynamic Properties of ATP
• Differences between ∆G’ and ∆Go’
• Major Metabolic Control Mechanisms
Experimental Analysis of Metabolism
• Since metabolism consists of all the chemical
reactions, to study it, to subdivide it into something
that can be studied, biochemists seek:
• 1) to identify reactants, products, and cofactors ,
plus stoichiometry, for each reaction involved
• 2) to understand how the rate of each reaction is
controlled in the tissue of origin
• 3) to identify the physiological function of each
reaction and control mechanism