Carbohydrate metabolism 4-5 (wk4)

Question 1

Describe oxidative phosphorylation

Answer 1

-Oxidative phosphorylation -> Oxidative phosphorylation is an aerobic metabolic pathway with a high energy yield taking place in the mitochondrial intermembrane space and matrix: Reactants = 8 NADH and 4 FADH2 and Products = 26 ATP + 6 CO2 + 6H2O
-Oxidative phosphorylation -> Spontaneous electron flow through each of complexes I, III and IV (-∆G) is coupled to H+ ejection from the matrix to the intermembrane space. The energy released from the electron flow (-∆G) is used to pump free protons across the membrane, creating a proton concentration gradient. A total of 10 H+ are ejected from the mitochondrial matrix per 2 e- transferred from NADH to oxygen via the respiratory chain (6 H+ for FADH2 – because it enters at complex 2)

Question 2

Describe the key phases of the electron transport chain (ETC)

Answer 2

-ETC -> The ETC re-oxidises reduced coenzymes NADH and FADH2 back to their oxidised forms, NAD+ and FADH- releasing H- (2 electrons and 1 proton). These 2 electrons are then passed down a series of haem proteins embedded in the mitochondrial membrane, each ‘wanting’ the electrons more than the previous, with oxygen (aerobic) being the final electron acceptor and H2O produced (low energy end product). NAD+ and FADH are then recycled back to the cytosol and mitochondrial matrix.

Question 3

Describe the relationship between ATP yield and free energy change with regards to all the metabolic pathways covered
(Metabolism and free energy change, ATP synthase and oxidative phosphorylation)

Answer 3

-Metabolism and free energy change -> Gibbs free energy falls as electrons are transferred to FADH and NAD+ during glycolysis and the TCA cycle. NADH and FADH2 can be used to fuel ATP synthesis via the ETC and oxidative phosphorylation. NAD+ can be recycled back to glucose.
-ATP synthase -> ATP synthase is embedded in cristae of the inner mitochondrial membrane. ATP synthesis is directly related to 1) supply of ADP and Pi and 2) the proton gradient. The enzyme binds ADP + Pi when 4 protons are present, yielding 1 ATP molecule. 1 NADH —10 protons—- 2.5 ATP produced/ 1 FADH2—-6 protons—- 1.5 ATP produced.

-Oxidative phosphorylation -> Oxidative phosphorylation is an aerobic metabolic pathway with a high energy yield taking place in the mitochondrial intermembrane space and matrix. Reactants: 8 NADH and 4 FADH2, Product = 26 ATP.

Question 4

Draw the table for net energy yields from aerobic and anaerobic metabolism glucose
-For: glycolysis, pyruvate ox, krebs cycle, net gain, ox phos
-Includes -> substrate, main products, NADH and FADH gain, ATP net gain, protons, location, oxygen needed?

Question 5

Describe the role of NAD+ in bridging aerobic and anaerobic metabolism
-Limiting factors in aerobic metabolism, energy generating pathways, hydride ion

Answer 5

-Limiting factor in anaerobic metabolism -> Regeneration of NAD+. Increased ratio of NADH: NAD+ due to high ETC demand.
-Energy generating pathways -> Resynthesis of ATP is optimised for different activities by utilising different energy systems. These vary in maximal rates and also sustainability.
-Hydride Ion -> Breakdown of carbohydrates, lipids and protein can supply protons and electrons for chemical energy provision (ATP). When a substrate is oxidised it gives up 2 hydrogen atoms, passing one as a hydride ion (:H-) to NAD+ (to make NADH) and the other is released as a proton (H+) to the aqueous environment (lowers pH).

Question 6

Describe the anaerobic metabolism in muscle: Lactate

Answer 6

-Anaerobic metabolism in muscle: Lactate->
* Under aerobic conditions, glucose catabolism yields NADH to fuel high rates of ATP synthesis (30 ATP per 1 glucose) via oxidative phosphorylation.
* At high exercise intensities, the NADH: NAD+ ratio increases and the electron transport chain can’t regenerate NAD+ quick enough to maintain glycolysis
* As NADH is the product and NAD+ the reactant, many metabolic enzymes are inhibited by the accumulating NADH e.g. pyruvate dehydrogenase
* Under these anaerobic conditions e.g. sprinting events (100-400m), lactate is produced from pyruvate via lactate dehydrogenase, in turn regenerating NAD+.
* Muscle and blood (lactate) can increase from 1 to 30 mmol kg-1 during maximal exercise

Question 7

Describe aerobic v anaerobic metabolism
-ATP resynthesis rates during intense exercise

Answer 7

-PCr system: 2.6 mmol/ kg/ sec -1 (0.7 sec)
-Anaerobic CHO: 1.5 mmol/ kg/ sec -1 (5-60 sec)
-Aerobic CHO: 0.5 mmol/ kg/ sec -1 (>60 sec)

Question 8

Describe the lactate utilisation in muscle (3)

Answer 8

• Lactate production is associated with muscle fatigue and soreness during hard exercise, as muscle H+ production increases and cytosolic pH drops (~6.2), but is not a cause
• Lactate leaves active muscle fibres down a concentration gradient, entering less active muscle fibres, in turn reforming pyruvate
• Pyruvate can then be re-oxidised in less active muscle fibres to yield 14 ATP molecules via the pathways we have already discussed (TCA cycle and ETC/Oxidative phosphorylation)

Question 9

Describe the Cori Cycle and it’s importance in maintaining glucose supply to the exercising muscles

Answer 9

-Lactate utilisation in the liver ->
* Liver glycogen is a source of glucose during exercise
* During prolonged periods of exercise carbon skeletons from other molecules can be used to synthesise glucose for energy provision in muscle in a process called gluconeogenesis
* Lactate can leave fatiguing muscle, enter the liver via the blood and reform pyruvate. Pyruvate is then used as a substrate for gluconeogenesis and glucose shuttled back to fatiguing muscle fibres (Cori cycle)