Table of Contents
ELEMENT 4 - METABOLISM ................................................................................................ 1
4.1-4.5: Carbohydrate Metabolism ............................................................................................. 1
4.6: Metabolism of Adipose Tissue ............................................................................................. 7
4.7 & 4.8: Metabolism of the Liver ............................................................................................. 9
4.9: Role of Hormones .............................................................................................................. 12
4.10: G proteins in adrenergic and glucagon receptors ............................................................. 13
4.11: Glucagon and Adrenaline Metabolism ............................................................................. 15
4.12: Regulation of Hormone Secretion .................................................................................... 19
4.13: Glucocorticoid Action ...................................................................................................... 21
4.14 & 4.15: Insulin Signalling and Metabolic Effects ................................................................ 22
ELEMENT 4 - METABOLISM
4.1-4.5: Carbohydrate Metabolism
• Define what a carbohydrate is. Aldehydes or ketones with two or OH groups.
• What can carbohydrates be used for? As an energy source and for synthesis of nucleic acids
• What two types of glucose are there in the body? Straight chained and ringed
• What is their chemical difference? Ringed structure has an H2O removed
• What proportions do they exist in the body? 50/50
• Do they react differently? No, they’re interchangeable.
• What monomers are sucrose, maltose and galactose made from and what bonds are involved in
the joining of the monomers?
Monomers present Bonds involved
Maltose Glucose + glucose 1-4 glycosidic
Galactose Glucose + lactose 1-4 glycosidic
Sucrose Glucose + fructose 1-2 glycosidic
• Where are disaccharides broken down? In the small intestine
• Do people make equal amounts of sucrase, maltase and lactase? What are the clinical implications
of this? People make the same amounts of sucrase and maltase, but vary greatly in the amount of
lactase that they produce. This leads to varying degrees of ability in breaking down lactose, and
forms the basis for lactose intolerance. Those with small amounts or no lactase at all feel bloated
(because bacteria in the gut break lactose down somewhat, producing methane) and have diarrhea
(because the lactose in the gut increases the osmolarity, and water is unable to leave)
• Why can lactose intolerant people eat cheese? Because during cheese fermentation, lactoseàlactic
acid and so no need for the lactase enzyme.
• What is a genetic polymorphism and describe how lactose intolerance is an example of this. A
genetic polymorphism is where there are two or more alleles at the same locus in a gene and hence
various phenotypes. Lactase is produced in infant mammals to break down breast milk, but most
stop producing lactase in early childhood. Northern European humans are an exception (due to
drinking milk).
• What do “friendly bacteria” do in the gut? Convert lactose for us
• How can surgery of infections induce lactose intolerance? Minor reversible damage to the gut
sometimes causes lactase to stop being produced
,• What are the 3 glucose polymers, what bonds are involved and what enzymes break them down?
Starch Cellulose Glycogen
Bonds involved α1-4 glycosidic β1-4 glycosidic 1-4 glycosidic (for
main chain) and 1-6
glycosidic (for
branching)
Breakdown enzymes Amylase Can’t in humans See later
• What’s the normal range of glucose osmolarity? 4-6mM
• Why is high concentrations of glucose bad and what can happen if its too high? Glucose is a
reactive molecule and can cause damage to the plasma membrane of cells. The endothelial lining of
the CV system (especially narrow vessels) is particularly vulnerable to this. This can cause blindness
(as the vessels of the retina can be affected) and large cysts/sores/necrotic areas in the extremities
such as legs and feet.
• What are the major glycogen stores in the body? Muscle (larger store) and liver
• What is glycogen stored in, inside the cell? As small insoluble granules
• Why is glycogen insoluble and how is this beneficial? Because the molecule is so massive and
branched. Its insolubility is ideal because it allows glucose to be stored, without it affected the
osmotic gradients of surrounding tissues like glucose does.
• Describe the process of glycogen synthesis.
Step Enzyme Molecule after reaction step
Addition of phosphate Hexokinase
to glucose, trapping (requires ATP)
glucose in the cell.
This step requires the
hydrolysis of ATP.
Movement of the Phosphoglucom
phosphate from the utase
C6 position to the C1
position
, An enzyme swaps the UDP-glucose
phosphate group for a pyrophosphoryl
uridine diphosphate ase (requires
molecule. A UTP UTP)
molecule is also
required to give
energy to the
reaction.
UTPàUDP+Pi
(phosphate ion is
released). This step
puts energy onto the
glucose molecule
Glycogen synthase Glycogen
then adds the synthase
“primed” glucose
(UDP-glucose) onto a
growing glycogen
strand of at least 4.
A branch is formed Branching
every 6-12 glucoses enzyme
forming the 1-6
glycosidic bonds
• Describe the process of glycogen breakdown. It’s effectively the reverse reaction. A debranching
enzyme debranches the molecule. Glycogen phosphorylase (with a free Pi) cleaves off glucose one at
a time, and adds the phosphate onto it, forming glucose-1-phosphate. Phosphoglucomutase moves
the phosphate to the C6 position. In muscle cells, the process ends here and the glucose can go into
glycolysis if needed. In the liver, however, glucose-6-phosphatase removes the phosphate to form
glucose, which goes off into the blood stream (occurs during fasting state).
• What are three glycogen storage diseases?
1. Type 1a (Von Gierke’s) – is a mutation in the glucose-6-phosphatase enzyme, and therefore
glucose is trapped within liver cells as it cant be turned into glucose. This leads to
hypoglycaemic susceptibility (treated by snacking, glucose drip/cornflour before sleep) and
hepatomegaly (swollen liver – glucose cant escape)
2. Type 3 (Cori’s) – defects in debranching enzyme, but most can be broken down. Leads to
mild hepatomegaly and hypoglycaemia
3. Type 5 (McArdle’s) – absence of muscle phosphorylase so glycogen stores in muscles can be
broken down. Leads to being able to exercise for not very long and muscle cramps (as
respiration becomes anaerobic much quicker)
• What is glycolysis? The production of 2x pyruvate from a glucose molecule, forming 2 NADH
moecules and two net ATP molecules
• How does pyruvate enter the mitochondria? Via a countertransport mechanism that brings
pyruvate into the matrix, and OH- out of the matrix (counteracting H+ gradient)
• What is PDH? Pyruvate dehydrogenase, the enzyme which catalyses the link reaction and feeds
pyruvate into the Krebs cycle as acetyl-CoA.
• Why is it called a multi-subunit complex? Because it consists of three enzymes: E1, E2 & E3.
• What does each enzyme do? E1 decarboxylates pyruvate. E2 adds acetyl to CoA to form acetyl CoA.
These two steps reduce the PDH complex, which inactivates it (as PDH is only active when its
oxidised). E3 is responsible for making the PDH complex active again, by reoxidising it, hence
reducing NAD to NADH in the process.
, • Why does a deficiency in vitamin B1 cause impaired glucose usage? Because PDH cannot function
without it and therefore pyruvate builds up and the TCA cannot occur as there’s no acetyl-CoA.
• Which organs do this affect the most? Brain, as it has a high glucose need.
• Why are alcoholics especially at risk of developing Wernicke’s disease? Alcoholics are likely to have
a bad diet and not consume a lot of vitamin B1 AND alcohol destroys vitamin B1. PDH cannot function
without vitamin B1.
• What vitamin B1 deficiency diseases/consequences should we know about?
1. Beriberi – neurological and CV disorders, prevalent in people who eat mainly white rice only
(note that brown rice had the vitamins)
2. Wernicke’s disease – see above. Affects thalamus and hypothalamus and causes confusion,
ataxia (“drunk-like’ symptoms) and nystagmus (flickering eye). Standard A&E treatment
would be glucose and saline for a drunk, but this would make this particular patient worse
and cause even more increase buildup of pyruvate. Instead, vitamin B1 should be given.
3. Korsakoff’s psychosis – a progression of the above where irreversible damage is done and
confabulation and memory loss occurs.
4. (Lactic acidosis – PDH doesn’t convert pyruvate into acetyl Co-A and so aerobic respiration
cannot occur, and instead pyruvate is converted into lactic acid, reducing blood pH.) – not as
relevant as liver often mops this problem up
• Do cytoplasmic and mitochondrial NADH pools ever mix? No, hence the need for shuttles
• How does NADH enter the mitochondria in the muscle and brain? The glycerol-3-phosphate
shuttle. This shuttle involves an energy loss as a reduced cytoplasmic NADH is traded for
mitochondrial FADH2.
• What is the enzyme involved in this shuttle? Glycerol-3DPH
• How does NADH enter the
mitochondria in the liver and the
heart? The malate-aspartate
shuttle. No energy loss as NADH is
traded for NADH.
• Why is reducing pyruvate to
lactate beneficial? It regenerates
NAD+, and prevents the buildup
of pyruvate, allowing glycolysis to
continue and some ATP to be
made.
• During anaerobic respiration,
pyruvate is reduced to lactate. How is this “debt” repaid once oxygen partial pressure is restored?
Lactate dehydrogenase enzyme oxidised lactate to become pyruvate again.
• How does lactate excreted into the blood? Through a lactate transporter, which symports a lactate
molecule with a proton.
• Is lactate ever used as a fuel? Yes, its used as the a fuel for the heart, which turns it back into
pyruvate. It is also used as the sole fuel for early embryos, as the lactate transporter is expressed
first.
• What is the Cori cycle? The cycle of lactate and protons which occurs between anaerobically
respiring tissues (glucoseàlactate/H+) and the liver doing gluconeogenesis (lactate/H+àglucose).
• How does blood loss inhibit the Cori cycle and hence cause acidosis? Because during massive blood
loss, blood is diverted away from the unessential abdominal organs and towards the heart and brain.
This means the liver receives less blood and so lactate and protons are not removed from the blood
à acidosis.
• How could you treat acidosis? A bicarbonate infusion, which neutralises the excess acid.
• What’s the difference between “white meat” and brown meat”?
