• Explain how the TCA cycle is regulated
energy availability
- ATP/ADP ratio
- NADH/NAD+ ratio
a-ketoglutarate dehydrogenase
isocitrate dehydrogenase
- rate limiting enzyme
Describe the key features of oxidative phosphorylation, explain the processes of electron transport and ATP synthesis and how they are coupled.
- electrons transferred from NADH & FAD2H through series of carrier molecules to O2, with release of energy
- H+ moved across inner membrane
- H+ gradient generated across inner mitochondrial membrane = proton motive force (pmf)
- return of H+ energetically favoured by electrochemical potential
- H+ returns via ATP synthase
- energy from dissipation of pmf is coupled to synthesis of ATP from ADP
Why is more ATP synthesised with NADH than with FAD2H with oxidative phosphorylation
- electrons in NADH have more energy than in FAD2H
- NADH uses 3 PTCs (protein translocating complexes), while FAD2H uses 2- oxidation of 2 molecules of NADH synthesises 5 moles of ATP, whereas 3 moles of ATP for FAD2H
How is oxidative phosphorylation inhibited by high atp
- high [ATP]
- no ADP substrate for ATP synthase
- inward flow of H+ stops
- [H+] in inter-mitochondrial space increases
- prevents further H+ translocation
- stop electron transport
• Describe how, when and why uncoupling of these processes occurs in some tissues
e.g. dinitrophenol, dinitrocresol, fatty acids
- increases permeability of mitochondrial inner membrane to H+
- dissipates H+ gradient, reducing pmf
- no drive for ATP synthesis so no electrochemical gradient
describe the various classes of lipids
fatty acids - fuel molecules
triacylglycerols - fuel storage + insulation
phospholipids - components of membrane and plasma lipoprotein
eicosanoids - local meditators
ketone bodies C4 - water soluble fuel molecules
cholesterol - membrane + steroid hormone synthesis
cholesterol esters - cholesterol storage
bile acids and salts - lipid digestion
vitamins A, D, E, K
describe how dietary triacylglycerols are processed to produce energy
- broken down to glycerol + fatty acids
- converted back in GI tract
- packaged into lipoprotein (chylomicrons)
- released into circulation via lymphatics + carried to adipose tissues
- stored as triglycerides
- released as fatty acids when needed
- carried to tissues as albumin-fatty acid complex
• explain how, when and why ketone bodies are formed
- produced when acetyl coA is in excess
- low NAD+ substrate availability and NAPH product inhibition
- used by peripheral tissues (muscle)
- synthesised by liver mitochondria
fed state vs starvation state
fed state: insulin/glucagon is high
- lyase inhibited, reductase activated
- cholesterol synthesis occurs
starvation state: insulin/glucagon low
- opposite
- ketone body synthesis
Inhibition of oxidative phosphorylation
- inhibitors block electron transport by preventing acceptance of electrons by O2
- e.g. cyanide
Explain the key role of pyruvate dehydrogenase in glucose metabolism.
- oxidises pyruvate to acetyl CoA while reducing NAD+ → NADH + H+
- irreversible
what is pyruvate dehydrogenase sensitive to
- sensitive to vitamin B1 deficiency
- enzyme acitivy requires various coenzymes provided by B-vitamins
