Ground Rules of Metabolism

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Chapter 6

• Ground Rules of Metabolism

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6.1 Energy

• Potential Energy- capacity to do work (chemical
  energy- measured in kilocalories) transformed
  into
• Kinetic Energy- energy of motion (mechanical
  energy- move flagella or the whole body, bottom
  right)
• Electrochemical energy- moves charged
• ions in/out of cell (above, also seen in
• fuel cell technology)

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6.1 (cont.)

• First Law of Thermodynamics- total amount of
  energy remains constant
• No energy conversion can ever be 100 efficient
• Wasted energy dissipates into surroundings as
  heat- thermal energy
• Are we eventually going to lose all our energy to
  our surroundings?
• Any system becomes disorganized w/out energy to
  maintain it
• Entropy- measure of degree of disorder
• Second Law of Thermodynamics- entropy exists
  ex) Will the pyramids crumble? yes

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6.2 Energy and Cellular work

• Endergonic- results in net increase of usable
  energy occurs in photosynthetic cells, energy is
  taken in during the formation of glucose uphill
  reaction
• Exergonic- spontaneous reactions (down-hill)
  energy out
• (United Streamline video)

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6.2 (cont.)

• ATP- Adenosine triphosphate
• 5-C ring (ribose), nucleotide base
• adenine and 3 phosphate groups
• Phosphorylation (phosphate group transfer)
• is energetically favored and releases large amt.
  of usable energy
• ATP ? ADP Pi ? ATP (cyclical)
• Electron transfer reactions
• (oxidation-reduction) are key for driving
• the synthesis of ATP, which then drives Ca
• (see right) and Na/K pumps etc.
• (see video clip)

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6.3 Chemical Equilibrium in Cells

• Reactant(s) combine together, forming
  intermediates during the sequential reaction, to
  finally create the product(s)
• Energy Carriers (ie. ATP) activate enzymes (or
  RNAs) by phosphorylation to speed up reactions
• Cofactors (metal ions and coenzymes) pick up
  electrons, functional groups and give them to
  different sites
• Transport proteins help
• substances cross membranes
• Right- the substrate and cofactor form
• an intermediate with the enzyme before
• formation of the final product

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6.3 (cont.)

• Biosynthetic pathways- ex) photosynthesis small
  molecules used to build larger molecules w/
  higher bond energies must have energy inputs
  anabolic
• Degradative pathways- exergonic break down
  larger products to smaller ones with lower bond
  energies ex) aerobic respiration catabolic
• C6H12O6 O2 ? H2O CO2 energy (ATP)
• Three pathways cyclic (left), linear and
  branched (right)

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6.3 (cont.)

• Chemical Equilibrium occurs at a fixed pace and
  ratio of product and reactant formation
• Ex) glucose-6-phosphate converts to
  glucose-1-phosphate in a 191 ratio
• Law of Conservation of Mass- of elements in
  reactants of elements in products

?
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6.4 Electron Transfer Chain

• Energy is released efficiently in cells through a
  series of redox rxns.
• NADP is the e- transferring coenzyme in
  photosynthesis, NAD and FAD are counterparts
  NADPH, NADH and FADH2 are the reduced forms
• These pass on the H and e- FOR electron transfer
  chains they are transport enzymes, not proteins
• Right NADPH accepts e-
• at the end of a series of
• electron transfer chains

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6.4 (cont.)

• Electron transfer chains involve e- falling from
  higher excited states (or higher energy levels),
  losing energy at certain steps

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6.4 (cont.)

• Throughout this process, these e- would be
  attracted to what? _____
• During certain steps, components repel these H
  ions across the membrane, establishing a
  concentration gradient and electrical gradient
• The movement of these H ions back across the
  membrane (through transport proteins) drives the
  synthesis of ATP

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6.5 Enzymes and Energy Hills

• Enzymes are catalytic molecules that speed up
  rates of reactions
• Do not make anything happen that could not happen
  on its own
• They are not permanently altered or used up
  during the reaction
• The same enzyme usually catalyzes the forward and
  reverse reactions
• They are picky about their substrates
• Right The structure of thrombin (red is
  negative,
• blue is positive) and the receptor
  (arginine-glycine
• section) are necessary for thrombin to convert a
• certain protein into the clotting factor in RBC

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6.5 (cont.)

• Activation energy (Ea) is the minimum amount of
  collision energy required to get a reaction
  going enzymes speed up reactions by lowering the
  Ea

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6.6 How do enzymes lower Ea?

• Active sites -pockets or crevices where enzyme
  binds to substrate (region that complements the
  enzyme in shape, size, solubility and charge)
• Sometimes cofactors help out (metal ions or
  coenzymes) sometimes cofactors are so tightly
  bound to active site they are prosthetic groups
  ex) heme group of hemoglobin
• Right The active site of EP24.15 (mammalian
  zinc
• peptidase) includes four helix bundles and loops
  this
• enzyme is involved with neuropeptide regulations
  and
• is linked to Alzheimers and Schizophrenia
• Left Immuno-reactivity
• regions in hippocampus
• and cortex of
• alzheimers patient

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6.6 (cont.)

• The enzyme is bound most tightly to substrate in
  the transition state, the point when the reaction
  can run easily in either direction to obtain
  chemical equilibrium
• Possible ways of reaching this transition state?
• (There are 5 possibilitiesthink about it, look
  back in your notes)
• Binding energy is the sum of all energies
  released from the weak bond interactions when
  intermediates form, which drives the formation of
  the transition state, enzyme-substrate complex
• Right General model of an enzyme binding
• to its substrate to form the transition state

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6.6 4 mechanisms for how binding energy can
speed up a reaction

• Helping substrates get together. By boosting the
  substrates, a reaction rate can increase x1000
• Orienting substrates in positions favoring
  reactions. Make weak bonds that place reactive
  groups as prime targets at active site
• Shutting out water. Making an active site
  non-polar can lower the Ea up to x 500,000 lower
  ex) attaching a carboxyl group (COO-)
• Inducing changes in enzyme shape. Induced-fit
  model- the substrate bends to accommodate
  functional group binding with enzyme
• Right Induced-fit model

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6.6 (cont.)

• Cofactors mediate electron transfers
• and other stabilizing events during
• intermediate formation ex) Heme
• has an Fe2 center that can bind with
• an O from H2O2 to push the formation
• of the transition state (pg.107)
• Enzymes are large repeated
• folding 1. creates an open active
• site for substrate binding and
• 2. provides structural stability

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6.7 Enzymes are controlled when conditions are
unfavorable

• Allo-(different)-steric-(structure)
• control- the active site
• changes to prevent binding
• Feedback inhibition-a loop
• starts and ends at an allosteric
• Recognition proteins (hormones)
• Also regulate enzyme activity
• Below general pattern for feedback
• inhibition

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6.7-6.8 Practical applications

• Extreme temperature changes disrupt metabolism
  (ie. fever 112 usually do not survive
• Most enzymes function in pH 6-8 ex) intestinal
  enzyme trypsin protein digesting enzyme pepsin
  functions in pH 1-2
• High salinity (NaCl) prohibits enzyme function
• Left Healthy liver alcohol dehydrogenase and
  other enzymes are working to break down alcohol
• Right Heavy drinkers kill liver cells, thereby
  reducing the of enzymes that can break down
  alcohol. The liver becomes consumed with fatty
  tissue, resulting in cirrhosis of the liver

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6.9 Bioluminescence

• Enzymes called Luciferases convert chemical
  energy to light energy
• ATP transfers a phosphate to luciferin
  (fluorescent substance)
• This destabilizes molecule, causing an e-
  transfer chain (mediated by luciferase)
• Some energy is released as fluorescent light
• Bioluminescence found in worms
• (left) and bacteria (right) can
  be
• used in research applications to
• track antibiotic resistant
  bacteria