Download Overview of metabolism

Overview of
metabolism
http://www.youtube.com/watch?v=kN5MtqAB_Yc
Autotrophs
• Such as photosynthetic bacteria and
vascular plants.
• It can use carbon dioxide from the
atmosphere as their sole source of
carbon, from which they construct all
their carbon containing biomolecules.
• Autotrophic cells and organisms are
relatively self-sufficient.
Heterotrophs
• It must obtain carbon from their
environment in the form of relatively
complex organic molecules such as
glucose.
• Multicellular animals and most
microorganisms are heterotrophic.
• It must subsist on the products of other
organisms.
Metabolism
Metabolism
The sum of all the chemical
transformations taking place in a cell or
organism occurs through a series of
enzyme-catalyzed reactions that
constitute metabolic pathways.
Catabolism
• Is the degradative phase of metabolism in
which organic nutrient molecules
(carbohydrates, fats, and proteins) are
converted into smaller, simpler end
products (such as lactic acid, CO2, NH3).
• Catabolic pathways release energy, some
of which is conserved in the formation of
ATP and reduced electron carriers (NADH,
NADPH, and FADH2); the rest is lost as
heat.
Anabolism
Also called biosynthesis, small, simple
precursors are built up into larger and
more complex molecules, including
lipids, polysaccharides, proteins, and
nucleic acids.
Anabolic reactions require an input of
energy, generally in the form of the
phosphoryl group transfer potential of
ATP and the reducing power of NADH,
NADPH, and FADH2
Generally
• Some metabolic pathways are linear,
and some are branched, yielding
multiple useful end products from a
single precursor or converting
several starting materials into a
single product.
• In general, catabolic pathways are
convergent and anabolic pathways
divergent.
Generally
• Some metabolic pathways are linear,
and some are branched, yielding
multiple useful end products from a
single precursor or converting
several starting materials into a
single product.
• In general, catabolic pathways are
convergent and anabolic pathways
divergent.
Generally
Some pathways are cyclic: one starting
component of the pathway is
regenerated in a series of reactions
that
converts
another
starting
component into a product.
All oxidative steps in the degradation
of carbohydrates, fats, and amino acids
converge at this final stage of cellular
respiration, in which the energy of
oxidation drives the synthesis of ATP.
Generally
In eukaryotes, oxidative phosphorylation
occurs in mitochondria. Oxidative
phosphorylation involves the reduction
of O2 to H2O with electrons donated by
NADH and FADH2.
Biological
oxidation
NADH:ubiquinone
oxidoreductase (Complex I).
NADH:ubiquinone oxidoreductase
(Complex I).
Complex I catalyze the transfer of a
hydride ion from NADH to FMN, from
which two electrons pass through a series
of Fe-S centers to the iron sulfur protein
N-2 in the matrix arm of the complex.
Electron transfer from N-2 to ubiquinone
on the membrane arm forms QH2, which
diffuses into the lipid bilayer.
This electron transfer also drives the expulsion from
the matrix of four protons per pair of electrons.
Complex I is inhibited by rotenone (a natural toxic plant
product), amobarbital (a barbiturate), andpiericidin A
(an antibiotic)
Electrons from succinate pass through a
flavoprotein and several Fe-S centers (in
Complex II) on the way to Q.
Glycerol 3- phosphate donates electrons to a
flavoprotein
(glycerol
3-phosphate
dehydrogenase) on the outer face of the inner
mitochondrial membrane, from which they
pass to Q.
Acyl-CoA dehydrogenase (the first enzyme of
β- oxidation) transfers electrons to electron
transferring flavoprotein (ETF), from which
they pass to Q via ETF:ubiquinone
oxidoreductase.
Oxaloacetate and malonate are competitive
inhibitors of succinate dehydrogenase and
compete with the substrate for binding at the
active site.
Carboxin and thenoyltrifluoroacetone inhibit
electron transfer from FADH2 to CoQ.
Complex III: Ubiquinone to Cytochrome c
The next respiratory complex, Complex III,
also called cytochrome bc1 complex or
ubiquinone: cytochrome c oxidoreductase,
couples the transfer of electrons from
ubiquinol (QH2) to cytochrome c with the
vectorial transport of protons from the matrix
to the intermembrane space.
Cytochrome c1 and the Rieske iron-sulfur
protein project from the P surface and can
interact with cytochrome c (not part of the
functional complex) in the intermembrane
space.
Antimycin A, an antibiotic that inhibits
electron transport from CoQ to cytochrome c.
Path of electrons through Complex IV.
• Electron transfer through Complex IV
begins when two molecules of reduced
cytochrome c each donate an electron
to the binuclear center CuA.
• From here electrons pass through
heme a to the Fe- Cu center
(cytochrome a3 and CuB). Oxygen now
binds to heme a3 and is reduced to its
peroxy derivative by two electrons
from the Fe-Cu center.
• Delivery of two more electrons from
cytochrome c (making four electrons
in all) converts the two molecules of
water, with consumption of four
“substrate” protons from the matrix.
At the same time, four more protons
are pumped from the matrix by an as
yet unknown mechanism.
• Cytochrome oxidase is inhibited by
cyanide, carbon monoxide, and azide.
Chemiosmotic model
• electrons from NADH and other oxidizable
substrates pass through a chain of carriers
arranged asymmetrically in the inner
membrane.
• Electron flow is accompanied by proton transfer
across the membrane, producing both a
chemical gradient (ΔpH) and an electrical
gradient.
• The inner mitochondrial membrane is
impermeable to protons; protons can reenter
the matrix only through proton-specific
channels (Fo). The proton-motive force that
drives protons back into the matrix provides
the energy for ATP synthesis, catalyzed by the
F1 complex associated with Fo.
Inhibitors of Respiratory Chain
These inhibitors block hydrogen or electron transfer along the chain and
are grouped into three groups.
At Complex I: They prevent utilization of NADH as a substrate, e.g.,
barbiturates (sedatives and hypnotics), rotenone (a fish poison and
insecticide), piericidin A (an antibiotic) and amytal.
At Complex II: They inhibit succinate dehydrogenase, e.g., malonate or
inhibit the succinate-Q reductase, e.g., Carboxin.
At Complex III: e.g., dimercaprol (used as anti-arsenic) and antimycin A
(an antibiotic). They lead to release of H2O2.
At Complex IV: e.g., cyanides, azide, carbon monoxide and hydrogen
sulfide.
At Complex V: They prevent ATP synthesis from ADP + Pi, e.g.,
oligomycin that also inhibits all the other complexes.
Inhibitors of oxidative
phosphorylation (uncouplers)
They inhibit oxidative phosphorylation
by disconnecting phosphorylation (ADP
+ Pi  ATP) from oxidation steps in the
respiratory chain.
Thus, there will be no ATP production
although oxidation steps in the
respiratory chain are running.
This is due to dissipation of the H+
electrochemical gradient.
Thermogenins: They are uncoupler
protein channels in the inner
mitochondrial membrane of the brown
adipose tissue in newborn animals.
Calcium Injection: Injection of calcium
dissipates H+ gradient used for transport
of Ca2+ into mitochondria and liberating
free heat and leads to the sensation of
increased body temperature.
Thyroxine: High concentration of
thyroxine dissipates H+ gradient and
increasing oxygen consumption.
Progesterone: The release of
progesterone at the mid-menstrual
cycle during ovulation interferes with
the oxidative phosphorylation. This
increases the female’s body temp. by
about 0.5oC that is used as an indicator
for time of ovulation.
Chlorpromazine: It is an antiemetic
drug used to prevent vomiting.
Dicumarol, Dinitrophenol, dinitrocresol, pentachloro-phenol : They work
+
as H channel in mitochondrial
membrane
dissipating
the
electrochemical gradient as free heat
and no ATP is produced. They were
used in treatment of obese persons to
reduce their weight.
Arsenic compounds: It interferes by
being used instead of Pi generating no
ATP (see glycolysis). Arsenic is a
cumulative toxin, i.e., when it is taken in
diet in small amounts it accumulates in
the body until it reaches its lethal level
leading to death.
Oligomycin: This is a fungicidal drug that
inhibits ATP synthase.