Metabolic Adaptation

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Metabolic Adaptation
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What is an adaptation?

• An evolutionary modification of the
  characteristics of an organism that facilitates
  an enhanced ability to survive and reproduce in a
  particular environment, or to exploit a new
  environment.

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What do metabolic adaptations do?

• Protect cellular function in the face of
  environmental challenge.
• Modulate energy supply in response to energy
  demand.

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What aspects of energy metabolism can provide
material for the operation of natural selection?

• Fuels/energy storage forms
• Pathways/energy yields
• Endproducts

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Choosing a fuelcarbohydrate vs fat

• Energy yield for complete oxidation of 6 glucose
  carbons is 28 ATP total or about 4.6 ATP/C
• Energy yield for complete oxidation of a 16C
  fatty acid (palmitic acid) is about 91.8 ATP
  total or a little less than 6 ATP/C
• So, we can get more energy from fat carbons than
  glucose carbons (i.e. fat is a more reduced
  material than carbohydrate) but the difference
  isnt huge.

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Fat vs carbs, round 2

• However, on an ATP/gram basis, the difference is
  huge a gram of fat gives us more than twice the
  energy of a gram of glycogen.
• This is especially important because an animal
  has to carry its stored fuel around with it.

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Fat is hard to transfer from place to place

• There is a down side to fat moving fatty acids
  through the bloodstream at a high rate is a
  challenge because they are not very
  water-soluble. Fat can be moved, but only as a
  complex with carrier protein that surrounds it,
  forming a lipoprotein. Similar carrier proteins
  are present in cytoplasm.
• Furthermore, to leave cells or enter them, most
  triacyglycerols must undergo lipolysis.

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It is hard to get energy from fat quickly
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Reliance on anaerobic glycolysis increases as
power output increases
In this graph, the highest rates of power output
are sustained by drawing on creatine phosphate
stores to recharge ATP stores but this can be
sustained for only a few tens of seconds at most.
The term fermentation in this graph refers to
anaerobic glucose metabolism with glycogen as the
startpoint.
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Choosing a fuel carbohydrate versus protein

• Amino acids and carbohydrates are at about the
  same oxidation state so although the exact
  pathways may vary from one amino acid to another,
  the yield of ATP from a gram of amino acid is
  about the same as the yield from a gram of
  glucose.
• However, as in the example of the fly, amino
  acids can be useful in anapleurotic pathways.
• Proteins frequently are catabolized to meet
  energy needs.

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Adaptation at the level of organs/tissues heart
versus brain

• Mammalian brain and heart are both highly
  dependent on oxidative metabolism
• The brain is highly adapted to get its AcetylCoA
  from glycolysis
• In contrast, the heart can metabolize fatty
  acids, lactate and some amino acids as well as
  glucose.

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Adaptation of skeletal muscle

• Type I red slowly fatiguing slow twitch muscle
  preferentially metabolizes fatty acids but can
  utilize glucose-derived pyruvate
• Type IIB white rapidly fatiguing fast twitch
  muscle must utilize glucose or glycogen
  because few or no mitochondria are present.

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Properties of skeletal muscle fibers that relate
to metabolic strategy

• Slow twitch
• Smaller fiber diameter
• Abundant myoglobin
• Small glycogen stores
• Fat stores may be abundant
• Many capillaries

• Fast twitch
• Larger fiber diameter
• Little/no myoglobin
• Extensive glycogen stores
• Few capillaries

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Hypoxia tolerance - Adaptation at the level of
the whole organism 3 kinds of examples

• Infant mammals vs adult mammals
• Fetal heart and brain are significantly more able
  to tolerate low oxygen levels than adult organs.
• High altitude animals vs low altitude animals
• At high altitudes, oxygen is delivered to the
  cells at a lower partial pressure than near sea
  level, so the oxygen affinities of both
  hemoglobin (the oxygen carrier) and cytochrome
  oxidase (the oxygen acceptor) have been increased
  (an evolutionary process) as species adapted to
  live at high altitude.
• Lower vertebrates vs typical mammals
• Some vertebrates can live for phenomenally long
  periods without oxygen aquatic turtles are
  apparently the champs in this the heart and
  brain of the turtle must therefore be able to
  subsist entirely through the glycolytic pathway
  and the animal must have large glycogen stores.

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The respiratory quotient is an indication of what
fuels are being metabolized

• The RQ is the ratio of CO2 produced/ O2 consumed.
• For glucose or glycogen as the starting material,
  the ratio is 1/1
• For fat as the starting material, the ratio can
  be as low as 0.7 when you think about this,
  remember that the O in the CO2 produced by
  oxidative metabolism comes from the fuel, not the
  atmosphere, and fat contains less oxygen per
  carbon than carbohydrate.
• RQ Values for protein lie between the values for
  fat and carbohydrate.

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Carbohydrate metabolism replaces fat metabolism
in exertion
In this example of the RQ of a hummingbird, the
RQ rises as the animal ends its nighttime rest
and starts foraging.
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In this example, a female salmon swimming upriver
to spawn, fat is used during the first part of
the journey when it is gone, protein is
catabolized glycogen (CHO) is saved for the
most intensively energetic parts of the trip
passing through rapids and especially for
building a nest and spawning at the end of the
journey.
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Thought question

• There is a hummingbird species that migrates on a
  path that crosses the Gulf of Mexico what fuel
  should it be using to do this?

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Mammalian brown fat Sometimes, a futile cycle is
OK

• Located around heart and around thorax and neck
  of infant humans and true hibernators.
• Brown color is due to abundant mitochondria in
  contrast to ordinary adipose tissue which is
  white fat.
• Epinephrine released in cold stress or spring
  rewarming causes production of uncoupling factors
  that induce a proton leak in inner mitochondrial
  membrane. Consequently, all of the free energy
  released by oxidative metabolism of fat appears
  as heat.

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Endproduct Adaptations

• The primary endproducts of amino acid catabolism
  are NH3 and CO2. The NH3 may be excreted as NH3,
  NH4, urea or uric acid.
• Which option is best depends on the species and
  life stage.

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Structures of ammonia, urea and uric acid
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Relative advantages and disadvantages of
different endproducts of protein catabolism

• Ammonia Carbon Dioxide
• NH3 is a gas that can be excreted as such (if you
  happen to have gills), or converted to NH4 under
  acidic conditions and thus trapped in solution
  this happens in urine formation for this
  mechanism of excretion, we are also automatically
  forced to excrete the CO2 as HCO3-
• NH3 is relatively toxic, especially to the brain
  of vertebrates
• NH3 is cheap to make, energetically

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Urea

• Urea
• readily soluble in water
• relatively non-toxic
• removes ammonia and carbon dioxide in
  stoichiometric amounts, preventing acid-base
  balance issues
• costly to make
• not just a wasteproduct - has a variety of
  possible uses in physiology ex. It is a
  critical component of the mammalian renal
  concentrating mechanism.

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Uric Acid

• Uric acid and its salts
• not very soluble in water readily form a
  crystalline precipitate when concentrated
• valuable for animals that form a solid urine to
  save water (insects, reptiles, birds), animals
  that estivate as a closed system (snails,
  lungfish) or ones that have to accumulate waste
  products in a closed system (bird and reptile
  eggs).
• In mammals, most of the relatively little uric
  acid produced is the result of purine catabolism.
  Disorders of uric acid excretion can lead to
  deposits of uric acid crystals in joints, i.e.
  gout. This is the most common form of
  inflammatory arthritis in adult men.

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The overall outcome of the urea cycle
The two N atoms of urea come from ammonia and
aspartate whereas the C comes from the HCO3-.
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Arginine and ornithine are potent stimulants of
growth hormone release in adults. Why does this
make metabolic sense?
Remember that glutamate serves as a common
collector of amino groups.
These are also the last three steps of the Krebs
cycle.
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Key features of the urea cycle

• 5 enzymatic reactions two are mitochondrial and
  3 are cytosolic. Ornithine can enter the
  mitochondria in exchange for citrulline, or by a
  separate process driven by the H gradient.
• The mitochondrial enzyme carbamoyl phosphate
  synthetase is a site of control of urea synthesis
  it is activated by increased glutamate
  concentrations that signal that an increase in
  deamination is happening.
• Amino groups from glutamate can be fed into the
  cycle at two different locations.

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Elevated SGOT is a clinical indicator of damage
to the liver

• SGOT is the abbreviation for serum glutamate
  oxaloacetate transaminase also called AST
  (aspartate aminotransferase). This enzyme is
  present in large amounts in liver cells and is
  released into the plasma by damaged cells in
  liver disease.