Category 2 Flashcards
(21 cards)
ATP is generated through subsrate level phosphorylation and oxidative phosphorylation. Approximately what percentage of ATP is generated through substrate level phosphorylation?
Lecture 1
10%
What are the 2 main purposes of the pentose-phosphate pathway?
Generates reducing power in the form of NADPH (an activated carrier). Generates ribose 5-phosphate, required for the synthesis of nucleic acids, precursor for nucleotides found in DNA and RNA.
Where in the cell do all reactions involved in the pentose phosphate pathway occur?
In the cytosol.
What are the functions of the activated carrier NADPH?
Mainly used in anabolic pathways. Required in synthesis of fatty acids, cholesterol, neurotransmitters and nucleotides. Also has a role in detoxification: the reduction of oxidised glutathione (must be reduced to be activated) which helps to detoxify molecules, particularly in erythrocytes.
What are the 2 main phases of the pentose-phosphate pathway and what do they each achieve?
Phase 1: Oxidative phase (generates NADPH and Ribose 5-phosphate, Phase 2: Non-Oxidative phase (converts ribose 5-phosphate into 3 and 6 carbon intermediates that can be fed into the glycolysis / gluconeogenesis pathway.
Describe the 3 enzyme-catalysed reactions that make up the oxidative phase of the pentose-phosphate pathway.
- Oxidation of Glucose 6-phosphate, generates NADPH.
- Hydration of this intermediate to form 6-Phosphoglucunate.
- Further oxidation: 6-Phosphogluconate oxidised to form Ribulose-5-phosphate and Carbon Dioxide.
All reactions are irreversible!
What is the sum of the reactions of the non-oxidative phase of the pentose-phosphate pathway?
3 (Ribose 5-Phosphate) <—–> 2 (Fructose 6-Phosphate) + Glyceraldehyde 3-Phosphate
What is the importance of the non-oxidative reactions of the pentose-phosphate pathway being reversible?
The process can flow into or out of glycolysis/gluconeogenesis, depending on cell requirements.
How might the cell use the pentose-phosphate pathway if it has high requirements for NADPH and ATP but has very low requirements for Ribose 5-Phosphate?
Both phases of the Pentose-Phosphate pathway are switched on, Ribose 5-phosphate generated in the oxidative phase is shuttled back into gluconeogenesis pathway as there is no need for Ribose 5-phosphate. The glucose 6-phosphate formed in gluconeogenesis can then go the the oxidative Phase 1 again, generating lots of NADPH.
What is the result of the glucose 6-phosphate dehydrogenase defiency? How do people get this deficiency?
Genetic basis, more common in areas prone to malaria. Cannot use pentose-phosphate pathway as efficiently, resulting in less NADPH. Lack of NADPH leads to lack of reduced glutathione, which is required to detoxify glucosides.
Why does deficiency in glucose-6-phosphate dehydrogenase lead to favism?
Fava beans and drugs used to treat malaria such as contain large quantities of glycosides, which cannot be detoxified due to the resulting lack of reduced glutathione.
What is the role of reduced glutathione (GSH) in the body?
GSH detoxifies glycosides (found in fava beans) and drugs such as hydroxychloroquine.
Why are fava beans and certain drugs harmful to people with G6PDH deficiency?
These substances require detoxification by GSH, which patients with G6PDH deficiency cannot produce sufficiently, leading to oxidative damage to red blood cells and haemolytic anaemia.
Which enzyme(s) of the citric acid cycle perform substrate-level phosphorylation?
Succinyl CoA Synthetase: Substrate-level phosphorylation is the production of ATP (or GTP) by transfer of a phosphate groups directly from another compound.
Which are the 3 enzymes that catalyse reactions in the citric acid cycle with a negative physiological ΔG - these are the regulation points?
Citrate Synthase, Isocitrate Dehydrogenase, α-ketoglutarate dehydrogenase.
What are the main activators of the citric acid cycle?
ADP (low energy signal) and Calcium ion (muscle contraction signal).
What are the main inhibitors of the citric acid cycle?
NADH and ATP (high energy / reducing power signals) and feedback inhibition.
How is the citric acid cycle inhibited in anaerobic conditions?
There is a build-up of NADH that cannot be oxidised into NAD+. NAD+ is required in the reaction that forms Acetyl CoA from pyruvate.
What is the Pyruvate Dehydrogenase Complex (PDC) and how is it regulated?
3 enzyme complex that catalyses conversion of pyruvate to acetyl CoA. It is regulated by reversible phosphorylation of E1: it is inactive when phosphorylated and active when dephosphorylated.
What are the roles and cofactors of the enzymes in the PDC?
E1 catalyses oxidative decarboxylation of pyruvate; cofactor: thiamine pyrophosphate (TPP).
E2 transfers the acetyl group to CoA; cofactor: lipoamide.
E3 regenerates oxidised lipoamide; cofactor: FAD.
What molecules regulate PDC activity and what is the sequence of reactions?
Kinase activators (inactivate PDC): ATP, NADH, acetyl CoA (high energy/product signals). Phosphatase activators (activate PDC): ADP, pyruvate, Ca²⁺ (low energy or muscle activity signals). Sequence: E1 catalyses decarboxylation, E2 transfers the acetyl group to CoA, E3 regenerates oxidised lipoamide.
