Lecture 3 - Carbo. & Lipids Flashcards
Pyruvate does not directly enter the TCA. It undergoes a reaction first. What is the reaction? Desc. the product of the reaction, the enzyme, location and what affects it.
[Reaction: Pyruvate + CoA + NAD+ –> Acetyl CoA + CO2 + NADH + H+]
- Pyruvate converted to acetyl CoA
- Enzyme: Pyruvate Dehydrogenase (PDH)
- Location: Mitochondrial matrix
- Requires cofactor –> sensitive to Vit. B1 deficiency
- Reaction is irreversible = key regulatory step
What inhibits and activates PDH?
Activate:
- Pyruvate
- NAD+
- ADP
- Insulin
- Dephosphorylation
Inhibit:
- Acetyl-coA
- NADH
- ATP
- Phosphorylation
What occurs if there is a PDH deficiency?
Lactic acidosis
What happens in stage 3 of carbohydrate metabolism?
name, products, location
- TCA/Krebs’ cycle
- Pyruvate –> Acetyl CoA –> X3 NADH, X1 GTP/ATP, X1 FADH2
[so its x2 of everything because glucose –> x2 pyruvate] - Occurs in mitochondria matrix
- Catalytic cycle = oxaloacetate is regenerated = no net synthesis or degradation of intermediates
- Acetate C-C bond is broken
What is achieved at the end of the TCA cycle?
- All C-C and C-H bonds are broken
- All C atoms are oxidised to CO2
- X6 NADH, X2 FADH2, X2 GTP
What is the use of reducing power in stage 4 of catabolism (ETC)?
Electrons of NADH & FADH2 transported through a series of electron carriers to O2 –> energy–> ATP (oxidative phosphorylation)
Describe the ETC
- Electrons from NADH & FADH2 –> electron transport carriers –> energy –> move H+ across membrane –> p.m.f
Which carrier transport H+ across mitochondrial membrane?
ATP synthase
How many electrons/ATP does NADH & FADH2 each generate?
- NADH uses 3 PTCs (proton-transporting complexes) –> higher p.m.f =more ATP –> 2.5 moles of ATP each
- FADH2 uses 2 –> 1.5 moles of ATP each
Desc. the regulation of oxidative phosphorylation
- Regulated by [ATP]
- High ATP = low ADP –> no substrate for ATO synthase –> inward flow of H+ stops –> [H+] ⬆️in intermembrane space –> ETC stops
How does cyanide affect the ETC?
- Acts as an inhibitor
- Prevents oxidation of NADH and FADH2
- Prevents acceptance of electrons by O2
How do uncouplers affect the ETC and oxidative phosphorylation? What are some examples of uncouplers?
- Increase the permeability of mitochondrial inner membrane to protons –> reduces p.m.f
- H+ enters mitochondria w/o ATP synthase –> heat
- No oxidative phosphorylation, ETC continues
- Examples: dinitrophenol, dinitrocresol, f.a
What other thing can inhibit oxidative phosphorylation other than uncouplers and inhibitors?
- Ox/Phos disease
- Genetic defects in proteins coded by mtDNA –> ⬇️ETC
What does brown adipose tissue contain? What is its function?
- Thermogenin (UCP 1): transport H+ back into mitochondria
- In response to cold –> noradrenaline (norepinephrine) activates:
i) Lipase –> F.A from TAG
ii) F.A oxidation –> NADH/FADH2 –> ETC
iii) F.a activate thermogenin –> heat - Found in neonates (x shiver)
What are the differences between oxidative and substrate-level phosphorylation?
Oxidative:
- Required membrane-associated complexes (PTC)
- Energy coupling = indirect = p.m.f
- Need O2
- Major source of ATP (32)
Sub:
- Require enzymes
- Energy coupling = direct = hydrolysis of bonds
- Small ATP generated
Describe the various classes of lipids
- F.a = fuel molecules
- TAG = Fuel storage and insulation
- Phospholipid = Plasma membrane
- Ketone bodies = Water sol. fuel mol.
- Cholesterol = steroid hormone synthesis
- Vitamin ADEK
Desc. the metabolism of TAG
- GI tract: Hydrolysis of lipids by pancreatic lipase –> F.a and glycerol
- Packaged into chylomicrons –> lymphatic –> adipose tissue –> TAG (released when needed)
Desc. F.A catabolism
- Occurs in mitochondria, requires O2
1. FA is activated (linking coenzyme A outside mito., enzyme is hormone sensitive lipase)
2. Transported into matrix via carnitine shuttle
3. FA undergo oxidation, 2C removed each time
4. FADH2, NADH, H2O released each 2C
How does the activation of FA occur?
- In the cytoplasm
- FA link to coenzyme A by fatty acyl CoA synthase –> form fatty acyl CoA
- Activated FA X cross mitochondrial membrane readily –> carnitine shuttle
What is the purpose of the carnitine shuttle?
What inhibits it?
- Transport activated FA
- Controls rate of FA oxidation
- Inhibited by malonyl CoA
- Defects can occur due to exercise intolerance
Features of FA metabolism
- β-oxidation of FA
- Mitochondrial
- Require O2
- 2C removed each cycle
- No ATP synthesis (AMP + Pi)
What can glycerol be metabolised into?
Metabolised in liver
- Glycerol –> G. P
[Glycerol kinase] - G.P –> TAG/ DHAP (NADH released when form DHAP)
What is the function of acetyl CoA?
- Converted to F.A (form TAG/phospholipid)
- Converted to CO2
- Converted to HMG (form ketone bodies/cholesterol)
What are the 3 types of ketone bodies and when are they formed?
(Normal range < 1mM)
- Acetoacetate, β-hydroxybutyrate, Acetone
- Produced in starvation or type 1 DM
Where are ketone bodies synthesised and how?
- Made by liver mitochondria
What do statin drugs inhibit?
- HMG-CoA reductase
- Prevent HMG-CoA to be converted to cholesterol
How is the production of ketone bodies regulated?
- Insulin/glucagon ratio is high (fed state) –> lyase is inhibited, reductase is activated –> cholesterol
- When I/G ratio is low –> lyase is activated –> ketone bodies
Is ketone bodies water sol. or X?
Water sol.
