Flashcards in Metabolism Session 3 - Energy production from Carbs and Lipids Deck (43):
List the catabolic roles of the TCA cycle
The catabolic role is to oxidise the acetyl group (CH3CO-) of acetylCoA to two molecules of carbon dioxide, with the concomitant reduction of NAD & FADH and formation of GTP. The NADH and FADH2 are subsequently oxidised via the respiratory chain to generate ATP by oxidative phosphorylation.
List the anabolic roles of the TCA cycle
The anabolic role is to provide intermediates for the synthesis of various important molecules such as haem, fatty acids, glutamate and aspartate
The TCA cycle plays also an important role in the conversion of several glucogenic amino acids to glucose.
What three things does the TCA cycle require?
NAD+, FAD and oxaloacetate.
What is added to NAD+ and FAD?
H+ and e-
Why are there no known defects in the TCA cycle?
They would be lethal
How molecules of ATP does the TCA cycle produce?
What do the C4, C5 and C6 carbon intermediates of the TCA cycle served as intermediates for?
C5 and C4 intermediates used for the synthesis of non-essential amino acids
C4 intermediates used for the synthesis of haem and glucose
C6 intermediates used for the synthesis of fatty acids
How is the TCA cycle regulated?
Inhibited by high energy signals, activated by low energy signals
Give an example of an enzyme which is rate limiting in the TCA cycle, and explain how it is regulated
Isocitrate dehydrogenase, inhibited by high energy NADH, activated by low energy ADP
Give two eventual results of stage 3 catabolism
All C-C bonds have been broken, and C-atoms oxidised to CO2
All C-H bonds have been broken, and H-atoms (H+ and e-) transferred to NAD+ and FAD.
Where does the energy from stage 3 catabolism go?
ATP/GTP formation (2 in glycolysis, 2 in the TCA cycle)
Chemical bond energy of the e- in NADH/FAD2H
What is important about NADH and FAD2H?
contain high energy electrons that can be transferred to oxygen through a series of carrier molecules, releasing large amounts of free energy.
What two things occur in oxidative phosphorylation?
Electron Transport, electrons in NADH and FAD2H are transferrerd through a series of carrier molecules to oxygen, releasing free energy.
ATP synthesis, the free energy released in electron transport drives ATP synthesis from ADP + Pi
Describe the key features of electron transport and explain how the proton motive force (p.m.f) is produced
- In electron transport electrons are transferred from NADH (and FAD2H) sequentially through a series of multi-component complexes to molecular oxygen with the release of free energy. Three of them also serve as proton translocating complexes.
- The free energy is used to move protons from the inside to the outside of the inner mitochondrial membrane.
- The membrane itself is impermeable to protons and as electron transport proceeds the proton concentration on the outside of the inner membrane increases.
- The chemical bond energy of the electrons is transformed into an electro-chemical potential difference of protons. This is known as the proton motive force (p.m.f).
How much pmf energy is required to generate one molecule of ATP?
Where does the energy required to generate ATP from the ATP synthases enzyme come from?
This energy is derived from the pmf that has been produced across the inner mitochondrial membrane by electron transport.
Protons can normally only re-enter the mitochondrial matrix via the ATP synthase complex, driving the synthesis of ATP from ADP and Pi.
What is the ratio of NADH to ATP production?
Same for FAD2H
The oxidation of 2 moles of NADH gives 5 moles of ATP
The oxidation of 2 moles of FAD2h gives 3 moles of ATP
What does it mean to say ET and ATP synthesis are tightly couple?
One does not occur without the other
How ATP concentration being high inhibit further ATP synthesis?
When ATP concentration is high:
The ADP concentration is low and the ATP synthase stops (lack of substrate)
This prevents H+ transport back into the mitochondria
The H+ concentration outside increases to a level that prevents more protons being pumped to the outside
In the absence of proton pumping, electron transport stops
What causes uncoupling, and what is it? Why is it important in the body?
Some substances (eg dinitrophenol, dinitrocresol) increase the permeability of the inner mitochondrial membrane to protons. Therefore protons being pumped out by electron transport can re-enter without passing through the ATP synthase complex.
The two processes become uncoupled so the p.m.f. is dissipated as heat.
Proton leak is physiologically important and accounts for 20-25% of the BMR.
Describe the roles of UCP-1, -2 and -3
UCP1 - (previously known as thermogenin) is expressed in brown adipose tissue and involved in non-shivering thermogenesis enabling mammals to survive the cold.
UCP2 – Quite widely distributed in the body. Research suggest it is linked to diabetes, obesity, metabolic syndrome and heart failure.
UCP3 – Found in skeletal muscle, brown adipose tissue and the heart. It appears to be involved in modifying fatty acid metabolism and in protecting against ROS damage.
How does noradrenaline increase uncoupling?
stimulates lipolysis releasing fatty acids to provide fuel for oxidation in brown adipose tissue. NADH and FAD2H are formed as a result of -oxidation of the fatty acids. NADH and FAD2H drive ET and increase p.m.f. However, noradrenaline also activates UCP1, allowing protons to cross the inner mitochondrial membrane without passing through the ATP synthase complex. The higher p.m.f. is dissipated as heat.
Give four key features of oxidative phosphorylation IMPORTANT KEEP ON YELLOW LEVEL MAX
Requires membrane associated complexes
(inner mitochondrial membrane)
Energy coupling occurs indirectly through generation and subsequent utilisation of a proton gradient (p.m.f.)
Cannot occur in the absence of oxygen
Major process for ATP synthesis in cells that require large amounts of energy
Give four key features of substrate level phosphorylation IMPORTANT KEEP ON YELLOW LEVEL MAX
Requires soluble enzymes.
(Cytoplasmic and mitochondrial matrix)
Energy coupling occurs directly through formation of a high energy of hydrolysis bond (phosphoryl-group transfer)
Can occur to a limited extent in absence of oxygen
Minor process for ATP synthesis in cells that require large amounts of energy
Give four fatty acids derivatives and their functions
Fatty Acids – Fuel molecules
Triacylglycerols – Fuel storage and insulation
Phospholipids – Components of membranes and plasma lipoproteins
Eicosanoids – Local mediators
Give four hydroxymethylglutaric acid derivatives and outline their roles
Ketone bodies (C4) – Water soluble fuel molecules
Cholesterol (C27) – Membranes and steroid hormone synthesis
Cholesterol esters – Cholesterol storage
Bile acids and salts (C24) – Lipid Digestion
Name the four fat soluble vitamins
How are tags digested, and what do they release?
Pancreatic lipases in the small intestine, and they release glycerol and fatty acids.
Requires BILE SALTS and a protein factors called COLIPASE
How is glycerol metabolised in the liver?
Phosphorylated by glycerol kinase, and then either enters TAG synthesis or become DHAP, entering glycolysis in process.
Why are fatty acids excellent energy stores?
hydrophobic and highly reduced molecules
Give an important dietary polyunsaturated fat, and explain why it is essential in the diet
Arachidonic acid is the starting point for the synthesis of the eicosanoids. Cannot be synthesised in the body.
How are fatty acids metabolised?
Via beta oxidation
How are fatty acids activated?
Linked to CoA via S-atom linkage
How do fatty acids enter mitochondrion
Special transport system that ultilises carnitine to shuttle the fatty acid across the inner mitochondrial membrane.
What inhibits transport of fatty acids into mitochondrion, and why?
Malonyl CoA - by product of fatty acid synthesis. Prevents fatty acids newly synthesised in cytoplasm from being oxidised in mitochondria.
How does Beta oxidation proceed?
Removal of 2 carbons from fatty acid at a time (acetate) to form acetyl CoA
Name three ketones produced in body
Acetoacetate – CH3COCH2COO-
Acetone – CH3COCH3 (Spontaneous non-enzymatic decarboxylation of above)
-hydroxybutyrate – CH3CHOHCH2COO-
When does ketone synthesis occur?
D Glucose U Glucagon U Lyase U Ketones and vice versa
What two things are required for ketone bodies to be produced?
Fatty acids to be available for oxidation in the liver following excessive lipolysis in adipose tissue – this supplies the substrate.
The plasma insulin/glucagon ratio to be low, usually due to a fall in plasma insulin – this activates the lyase and inhibits the reductase.
Name enzyme for each arrow
Acetyle coA --> hydroxymethylglutaryl coA --> Ketone
What enzyme is responsible for conversion of hydroxmethylglutarl coA to cholesterol?
How is acetyle coA produced?
by the catabolism of:
Certain amino acids