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Metabolic Adaptation
What is the actual yield of ATP from oxidative
phosphorylation?
2 NADH from glycolysis (about 1.5 ATP each)
3
2 NADH from pyruvate dehydrogenase (about 2.5 ATP each)
5
2 FADH2 from citric acid cycle (about 1.5 ATP each)
6 NADH from citric acid cycle (about 2.5 ATP each)
3
15
Total from gradient-mediated phosphorylation
26
2 ATP equivalents (GTP) from substrate-level
phosphorylation in TCA cycle
Total for oxidative metabolism only
2
28
(older calculations gave 36 or 38 ATP)
+2 ATP from substrate level phosphorylations in glycolysis
This is the approximate total yield of ATP starting with 1 glucose –
remember, it’s not a hard number or necessarily an integer
30
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.
What do metabolic adaptations do?
• Protect cellular function in the face of
environmental challenge.
• Modulate energy supply in response to
energy demand.
What aspects of energy metabolism can provide
material for the operation of natural selection?
• Fuels/energy storage forms
• Pathways/energy yields
• Endproducts
Choosing a fuel:carbohydrate 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
isn’t huge.
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.
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 watersoluble. 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.
It is hard to get energy from fat
quickly
Fuel/Pathway
Maximum Sustainable
Metabolic Rate in mammals
(microg ATP/g/min)
Fatty acid oxidation
20
Complete oxidation
starting with glycogen
30
Anaerobic glycolysis
starting with glucose
60
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.
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.
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.
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.
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
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.
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.
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.
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.
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?
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.
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.
Structures of ammonia, urea and uric acid
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
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.
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.
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-.
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.
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.
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.