Flashcards in Session 2 Deck (40):
What are the requirements for the TCA cycle?
Where does the TCA cycle occur?
What is the main function of the TCA pathway?
-Oxidise carbon atoms to CO2
-Transfer of H+ and e- to NAD+ and FAD
-Breaking of C-C bonds in acetate
-Production of ATP
What can the TCA cycle not function without?
What does the intermediates in the TCA cycle allow for in terms of biosynthesis?
-Fatty acid synthesis
What enzyme catalyses the conversion of pyruvate to oxaloacetate?
What are the characteristics of pyruvate dehydrogenase?
-Exist in the Mitochhondrial matrix
-Large multi complex (5 enzymes)
-Co-factors required leads to PDH being sensitive to vitamin B1 deficiency.
-Reaction is irreversible so is a key regulatory step
What is the result of PDH deficiency?
What are the ways in which isocitrate dehydrogenase is regulated?
-Stimulated by ADP
-Inhibited by NADH and ATP
What are the ways in which alpha-ketoglutarate dehydrogenase is regalated?
Inhibited by NADH, ATP, and Succinyl-CoA
What are the key characteristics of stage 4 catabolism of carbohydrates?
-NADH & FADH2 re-oxidised
-O2 required which is reduced to H2O
-Large amounts of energy int he form of ATP is produced
What is the use of reducing power in ATP synthesis?
-Electrons on NADH and FADH2 transferred through a series of carrier molecules to oxygen (ELECTRON TRANSPORT)
-Free energy released used to drive ATP synthesis (OXIDATIVE PHOSPHORYLATION)
What is the process of oxidative phosphorylation?
-Electrons are transferred from NADH and FADH2 through a series of carrier molecules to O2 with release of energy
-Energy used to move H+ across membrane
-H+ gradients is established across inner mitochondrial membrane. Proton motive force established
-Return of protons is favoured energetically by the electrochemical potential
-Protons can only return across membrane via the ATP synthase and this drives ATP synthesis
Electrons in NADH have more energy than in FADH2. true/false
How is oxidative phosphorylation regulated?
-When ATP is high (therefore ADP low) no substrate for ATP synthase
-Inward flow of H+ stops
-Concentration of H+ in the intermitochondrial space increases
-Prevents further H+ pumping - stops electron transport
What is an example of an inhibitor of oxidative phosphorylation?
-Cyanide, Carbon monoxide
-Blocks electron transport therefore prevents acceptance of electrons. Therefore no proton motive force so no oxidative phosphorylation
What are examples of uncouplers of oxidative phosphorylation?
How do they work?
-Dinitrophenol, Dinitrocresol, Fatty Acids
-Increases the permeability of membrane of H+
-H+ enters mitochondria without driving ATP synthase so dissipates proton motive force. No phosphorylation of ADP as a result so no inhibition of electron transport
What happens to energy lost during oxidative phosphorylation?
-It is lost as heat.
-Efficiency of oxidative phosphorylation depends on the tightness of coupling
What does brown adipose tissue contain that allows for heat generation in response to the cold?
-Contains thermogenin (UCP1)
-In response to the cold, noradrenaline activates
-Lipase triggers release of fatty acids from TAG
-Fatty acid oxidation occurs so NADH and FADH2 are formed.
-Electron transport can occur
-UCP1 transport H+ back into mitochondria
-Electron transport is uncoupled from ATP synthesis. Energy from the p.m.f is released as EXTRA HEAT
Oxidative VS Substrate level Phosphorylation
-Requires membrane associated complexes
-Energy coupling occurs indirectly through generation & subsequent utilisation of proton gradients
-Cannot occur in the absence of O2
-Major process for ATP synthesis in cells requiring large amounts of energy
Substrate level phosphorylation
-Requires soluble enzymes
-Energy coupling occurs directly through formation of high energy hydrolysis bone
-Can occur to a limited extent in the absence of O2
-Minor process for ATP synthesis in cells requiring large amounts of energy
What are the benefits of TAGs that allow it to be stored?
How is storage and mobilisation control?
-Hydrophobic therefore stored in anhydrous form in a specialised tissue called adipose tissue.
-Controlled by hormones
When are TAGs utilised?
-Utilised in prolonged exercise, starvation and during pregnancy
-Released as fatty acids when need and carried to tissues as albumin-fatty acid complex
How are TAGs in the diet metabolised and transported?
-TAGs in diet are hydrolysed by pancreatic lipase in small intestine to fatty acids and glycerol
-They are recombined back to TAGs in the G.I tract and packaged into lipoprotein particles (CHYLOMICRONS)
-They are released into circulation via lymphatics
-They are then carried to adipose tissue and stored as TAGs
How does fatty acid catabolism occur?
-Occurs in the mitochondria
1. Fatty acid is activated by linkage to co-enzyme A outside the mitochondrion by the action of 'fatty acyl CoA synthase'
2. The fatty acids is transported across the inner mitochondria membrane using a carnitine shuttle
3. Fatty Acid cycles through a sequence of oxidative reactions with 2 carbons being removed each cycle
How is the fatty acid oxidation regulated via the carnitine shuttle?
-Inhibition by malonyl CoA
(Defects can also occur in the transport system leading to exercise intolerance and lipid droplets in muscle)
Main points of Fatty acid metabolism?
-Cycle of reactions
-Removal of 2C units per cycle
-H+ and e- transferred to NAD+ and FAD
-Stops in absence of O2
-No ATP synthesis
What enzyme is used to convert glycerol to glycerol phosphate?
Where is glycerol metabolised?
Glycerol is transported in the blood to the LIVER
Which molecule acts as the main convergence point for catabolic and anabolic pathways?
How are they linked?
-Acetyl is linked to coenzyme A via S-atom
What vitamin does CoA contain?
What are 3 types of ketone bodies?
What are key ranges of ketone bodies?
-Normal plasma ketone body concentration = <1mM
-Stavation ketone body concentration = 2-10 mM (physiological ketosis)
-Untreated Type 1 diabetes = >10 mM
What do statin drugs act on?
Which enzyme is used to form cholesterol from acetyl CoA?
Which enzyme is used to form ketone bodies from acetyl CoA?
What are inhibitors of isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase in the TCA cycle?
-Low NAD+ substrate availability
-NADH product inhibition
What is activated when insulin/glucagon ratio is high?
HMG-CoA Reductase or Lyase
HMG-CoA reductase is activated
Lyase is inhibited
What is activated when insulin/glucagon ratio is low?
HMG-CoA Reductase or Lyase
HMG-CoA reductase is inhibited
Lyase is activated
What are the characteristics of ketone bodies?
-Water soluble molecules
-Permits relatively high plasma concentrations
-Above renal threshold, ketonuria occurs
-Acetoacetate and beta hydroxybutyrate are relatively strong organic acids so can lead to ketoacidosis
-Volatile acetone may be excreted via the lungs