METABOLIC BIOCHEMISTRY

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METABOLIC BIOCHEMISTRY

• Lecture 14
• Sept. 8, 2006
• Summary and Review

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• Metabolism
• - The overall process by which living systems
  acquire and utilize free energy to
• carry out biological work
• - The process by which a variety of small
  molecules are assembled from a few
• precursors the small molecules then serve as
  building blocks for
• macromolecular structures
• Metabolism can be organized into pathways these
  pathways may overlap,
• and branch, and even consist of circular paths
• A pathway consists of consecutive enzymatic
  reactions the reactants,
• intermediates and products are called metabolites
• - The flux through each pathway is regulated by a
  sophisticated set of
• metabolic regulatory mechanisms feedback
  inhibition, allosteric interactions,
• covalent modification of proteins/enzymes, etc.

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• -Metabolic pathways are irreversible at certain
  key steps where a large negative
• free energy change occurs the emphasis is on
  flux, not on isolated chemical equilibria
• -There are catabolic pathways (e.g.glycolysis)
  and anabolic pathways (e.g. gluconeogenesis)thes
  e are necessarily different at key steps, but may
  share some steps
• -In eukaryotic cells the various metabolic
  pathways are compartmentalized
• cytosol, mitochondria, peroxisomes, chloroplasts,
  etc.
• -The compartments are defined by membranes
  special transport mechanisms must
• exist to regulate the flow of reactants and
  products in and out of a compartment
• In some cases the flow is determined by a
  concentration gradient (diffusion), but
  stillrestricted by a specific transporter
• in other cases integral membrane proteins can act
  as pumps to pump metabolites
• and ions against a concentration gradient this
  requires an input of energy

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Why study metabolism and its regulation? 1. This
is what scientists do it is an intellectual
challenge The final result is satisfying and even
beautiful (although beauty is in the eye of the
beholder) 2. It turns out to have enormous
practical value in the maintenance of our good
health a) a common sense approach to
nutrition b) an intelligent response to false
advertising in understanding metabolic
diseases (inborn errors of metabolism) a)
diagnosis b) possible treatments c)
establishing a genetic basis d) genetic
counselling and prenatal diagnosis 3. you can
make a lot of money (drugs, inhibitors, etc.)
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Beware of the Quacks

• QuackwatchSM
• Your Guide to Health Fraud,
• Quackery, and Intelligent Decisions
• Operated by Stephen Barrett, M.D
• Great Smokies' Genovations Test
• http//www.quackwatch.org/index.html

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POWER WORK / TIME (Physics) TIME
MONEY (Business) KNOWLEDGE POWER
(Academia) WORK KNOWLEDGE
______________ (1) MONEY Solving for
money WORK MONEY _________________
KNOWLEDGE
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If the true essence of life is the accumulation
of experience through generations, then one may
perhaps suspect that the key problem in biology
from the physicists point of view is how living
matter manages to record and perpetuate the
experience Max Delbruck
Mitchells CHEMIOSMOTIC HYPOTHESIS is one of the
giant achievements of 20th century science It
can almost literally explain how solar energy can
be converted into force and kinetic energy (e.g.
muscular motion) or electrical signalling
between the brain and our peripheral nervous
system or power the assembly of
macromolecules or store information in
biological systems
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Fatty acids
Glycogen
Glyoxylate Cycle
Glucose
Acetyl-CoA
PEP
Krebs Cycle
Calvin Cycle
mevalonate
CO2
Cholesterol etc.
CO2
Urea Cycle
Electron Transport OXPHOS
Light Reactions
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KEGG Kyoto Encyclopedia of Genes and Genomes
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OMIM Online Mendelian Inheritance in Man
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glycolysis
gluconeogenesis
glucokinase
phosphatase
phosphofructokinase PFK-1
phosphatase
PEP carboxykinase
pyruvate kinase
pyruvate carboxylase
4 ATP, 2 GTP, 2 NADH needed
2 ATPs produced
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MUSCLE
LIVER
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b-oxidation of fatty acids
1. Activation in cytosol to acyl-CoA
2. Transacylation to form acyl-carnitine
3. Import into mitochondria
4. Transacylation to acyl-CoA
5. Four steps in b-oxidation
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1. in plants
2. long chain FA in animal cells
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Ketone bodies
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Oxidative phosphorylation in mitochondria
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4Fe-4S
2Fe-2S
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Photosynthesis in chloroplasts
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Fate of a photon absorbed by a molecule
1. Internal conversion kinetic energy rotations
and vibrations 2. Fluorescence a photon is
re-emitted, but at longer l 3. Exciton
transfer resonance energy transfer from one
molecule to another nearby molecule 4.
Photooxidation the excited molecule actually
loses an electron to form a cationic free
radical the free radical becomes a strong
oxidizing agent
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C3 C3 C6 C6 C6 C6 C3 C4
C5 C4 C3 C7 C7 C7 C7 C3 C5
C5
aldolase
phosphatase
transketolase
aldolase
phosphatase
transketolase
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Photorespiration
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Raising CO2 concentrations in C4 plants
alternate enzyme PEP carboxylase
cost 2 ATP (effectively)
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Cholesterol and isoprenoid synthesis
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important target for drugs to lower cholesterol
levels
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Goldstein and Brown Science 3111721-1723 (2006)
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Several important vitamins converted to
cofactors and their participation in various
reactions
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BIOTIN IS INVOLVED IN ACTIVATION OF CO2
IN CARBOXYLATION REACTIONS
e.g. pyruvate carboxylase
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BIOTIN IS INVOLVED IN ACTIVATION OF CO2
IN CARBOXYLATION REACTIONS
e.g. acetyl-CoA carboxylase
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Vitamin B12 (cobalamin)
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in pathway of propionyl-CoA utilization
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Involvement in decarboxylation reactions, e.g.
pyruvate
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Trace Metals in Metabolic Biochemistry
Fe electron transport chain Fe-S,
cytochromes Cu complex IV (mitochondria),
plastocyanin (chloroplasts) Mn oxygen
evolving complex in chloroplasts Co vitamin B12
Mg, Ca, too numerous to mention
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