Session 3 ILO's - Carbohydrates 3 and Energy production with lipids

Question 1

Explain the key role of pyruvate dehydrogenase in glucose metabolism.

Answer 1

• In poor O2 tissues, lactate dehydrogenate can metabolise pyruvate and NADH to produce NAD+ required for glycolysis of glucose
• It can also work to remove lactate in well oxygenate tissues by converting lactate and NAD+ into pyruvate and NADH

Question 2

Describe the roles of the tricarboxylic acid cycle (TCA cycle)/Krebs cycle in metabolism

Answer 2

Acetyl CoA is oxidised to produce 2 x CO2 and some energy produced by substrate level phosphorylation

Also produces precursors for biosynthesis:
Per cycle (x 2 for per glucose):
3 x NADH
1 x FADH2
1 x GTP
These can then be used to drive the electron transport chain to produce much more ATP

Question 3

Explain how the TCA cycle is regulated.

Answer 3

Regulation occurs at 2 enzymes :

1. Isocitrate dehydrogenase
2. Alpha-ketoglutarate dehydrogenase

• Both enzymes activated by low energy compounds e.g. AMP, NAD+
• Both enzymes inhibited by high energy compounds e.g. ATP, NADH

Question 4

Describe the key features of oxidative phosphorylation.

Answer 4

• Occurs in the mitochondria
• NADH & FADH2 are re-oxidised
• O2 is required (reduced to H2O - gains oxygen)
• Lots of ATP is produced

Question 5

Explain the processes of electron transport and ATP synthesis and how they are coupled.

Answer 5

• Electrons are transferred through a series of carrier molecules along to O2, with release of energy
• 30% of energy is used to move H+ across the membrane, whilst 70% is released as heat (maintain core body temp)
• Movement of the H+ across the membrane, creates a proton motive force and this drives the movement of H+ back across through the ATP synthase - which drives the conversion of ADP to ATP = energy production!!! :)

Question 6

Describe how, when and why uncoupling of these processes occurs in some tissues.

Answer 6

• Uncoupling increase the permeability of mitochondrial inner membrane to protons, which dissipates the proton motive force and hence there is less of a driving force for ATP synthesis
• Uncoupling occurs in brown adipose tissue (which contains UCP1) because it allows for extra heat generation and maintains heat in newborn infants
• Noradrenaline is released in response to cold, which actives lipases to release fatty acids which active UCP1 = heat generation

Question 7

Compare the processes of oxidative phosphorylation and substrate level phosphorylation.

Answer 7

• Substrate level phosphorylation (SLP) requires soluble enzymes, whereas Oxidative Phosphorylation (OP) requires membrane associated complexes
• SLP occurs directly through formation of high energy bonds, whereas OP uses p.m.f to indirectly generate energy coupling
• SLP can occur to an extent anaerobically, whereas OP cannot occur anaerobically
• SLP minorly contributes to ATP synthesis in cells requiring large amounts of energy, whereas OP is the major ATP generator!

Question 8

Describe the various classes of lipids.

Answer 8

1. Fatty Acid derivatives
   Fatty acids = fuel molecules
   Triacylglycerols (triglycerides) = fuel storage & insulation
   Phospholipids = components of membranes and plasma lipoproteins
   Eicosanoids = local mediators (signalling molecules between cells within tissues)
2. Hydroxy-methyl-glutaric acid derivatives
   Ketone bodies = water soluble fuel molecules
   Cholesterol = membranes and steroid hormone synthesis
   Cholesterol esters = form of cholesterol storage
   Bile acids & salts = lipid digestion
3. Vitamins
   A, D, E, K

Question 9

Describe how dietary triacylglycerol is processed to produce
energy.

Answer 9

• Triacylglycerol converted to fatty acids & glycerol by pancreatic lipases by process of lipolysis (in the gut)

-Fatty acids & glycerol are recombined in the small intestine and transported as Triacylglycerol by lipoproteins (chylomicrons)

• Lipoproteins carry these to the consumer tissues, where fatty acids are released and undergo fatty acid oxidation

Question 10

Explain how ketone bodies are formed.

Answer 10

• Ketone bodies are formed in the liver
• Acetyl-CoA is converted to Hydroxylmethyl glutaryl-CoA (HMG-CoA) by HMG-CoA synthase
• Hydroxylmethyl glutaryl-CoA (HMG-CoA) is converted to acetoacetate by HMG-CoA lyase
• Acetoacetate can then be converted to either acetone or Beta-hydroxybutyrate

Question 11

Explain when ketone bodies are formed.

Answer 11

• In low glucose states, fatty acids are mobilised and converted to Acetyl-CoA however this produces a lot of NADH which inhibits the enzymes in the Krebs Cycle (due to low NAD+) so Acetyl-CoA is diverted to make ketone bodies instead

Question 12

Explain why ketone bodies are formed.

Answer 12

• Ketone bodies are formed because they can still produce energy (when glucose is low indicating starvation)
  It spares glucose for use in the brain, if ketone bodies are being used for energy production in the muscles

Question 13

Describe the central role of acetyl~CoA in metabolism.

Answer 13

Acetyl-CoA is the main convergence point for catabolic pathways and can feed directly into the TCA cycle (produced from both carbohydrates and fatty acids)
Acetyl-CoA is the most important intermediate in both catabolic & anabolic pathways

Question 14

Outline fatty acid oxidation

Answer 14

• Occurs in the mitochondria
  Fatty acids are activated by linking to Coenzyme A outside the mitochondrion and are transported across the inter mitochrondrial membrane using a carnitine shuffle.
• Fatty acid cycles through a sequence of oxidative reactions with 2 x carbons removed each cycle
• Acetyl CoA can go into the Krebs Cycle (actually produces more energy from FA oxidation than glucose oxidation)

Question 15

Outline the 3 ketone bodies produced in the body

Answer 15

1. Acetoacetate
2. Acetate
3. Beta-hydroxybutyrate