T. brucei Glucose Metabolism Flashcards
In the bloodstream form of T. brucei, what is the primary carbon source?
Glucose
What is the metabolic mode used by bloodstream T. brucei?
Exclusively glycolysis (no TCA cycle or oxidative phosphorylation)
What is the final product of T. brucei glycolysis?
Pyruvate
What is the ATP yield from T. brucei glycolysis?
2 ATP (which is inefficient but sufficient)
Why is 2 ATP/glucose sufficient for bloodstream T. brucei?
Because human blood is very glucose-rich
What is the mitochondria function in bloodstream form?
Repressed- minimal function (only in NADH recycling)
What are glycosomes?
Specialised metabolic organelles in Trypanasomes that host the first seven glycolytic steps.
Similar structure to peroxisomes
What is the key difference between glycosomes and peroxisomes?
They have no catalase- tailored for glycolysis
What is the advantages of compartmentalising glycolysis (within the glycosome)?
- Segregates glycolysis from cytosol; removes need for allosteric regulation
- Helps maintain tight NAD+/NADH balance within glycosome
- Similar regulation (no feedback loops)
Why are glycosomes potential drug targets?
Glycosomal enzymes differ structurally from mammalian counterparts
How does T. brucei allow for continuous glycolysis?
Through NAD+ regeneration..
Ending glycolysis at pyruvate produces NADH, which must be oxidised back to NAD+ or glycolysis will halt
How does T. brucei regenerate NAD+?
Inside glycosomes, DHAP is turned into G3P by glycerol-3-phosphate dehydrogenase.
This uses NADH and regenerates NAD+
What happens once G3P is produced during regeneration of NAD+?
- G3P exists glycosome and donates electrons to ubiquinone in mitochondria
- Electrons transferred to oxygen via Trypanosome Alternative Oxidase (TAO), forming water
- DHAP (which is produced during reaction) is recycled back to glycosomes (continuous loop)
What is TAO?
An unusual mitochondrial oxidase (potential drug target)
What is the difference between nutrient availability in bloodstream and tsetse fly midgut?
Glucose is scarce in midgut- T. brucei must metabolically adapt
What are the main carbon sources in midgut?
- Proline
- Limited glucose
What is the reliance on the glycosome in procyclic form?
It is still important but less dominant, as other processes outside of simply glycolysis are used
What is the mitochondrial activity in pro cyclic form?
Fully active.
- Christie are more numerous and prominent (increases SA).
- Electron transport chain complexes 2, 3, 4 are active (roman numerals pls)
What is the difference in the structure of the mitochondria in bloodstream and midgut?
Bloodstream mitochondria = small, rudimentary and smooth
Procyclic mitochondria = expanded and remodelled, much greater SA
It is not simply are regulatory shift, but a profound ultrastructural change in mitochondria
What is the importance of glycolysis in procyclic form?
Glucose is still used if any available.
However, unlike bsf which stops at pyruvate excretion, pyruvate is instead converted in acetyl-CoA inside mitochondria.
Acetyl-CoA is then further metabolised
What occurs during mitochondrial oxidative metabolism in tsetse fly?
- Acetyl-CoA enters mitochondrial pathways
- Oxygen used as final electron acceptor
- Electron transport chain operates, generating proton gradient
- Proton gradient drives ATP synthesis via ATP synthase
How do procyclic T. brucei use TCA cycle?
They run a partial TCA cycle, which supports substrate-level phosphorylation
How does proline metabolism work?
Proline is oxidised by proline dehydrogenase
This feeds electrons into the ETC (bypassing glycolysis entirely)
This is crucial for ATP production when glucose is absent
What is the acetate:succinate CoA-Transferase cycle?
A newly discovered ATP-producing pathway that appears to dominate ATP production in procyclics
