Lecture 5/8: Parasite metabolism Flashcards
Why does genomics alone not always give the complete picture of which metabolic pathways are operational in an organism?
There are no fundamental differences between aerobic and anaerobic animal lineages in respect to the genes/enzymatic repertoire
Where do the cells get the pyruvate from that is part both panels in Fig 1? What external substrate is used to make pyruvate?
Pyruvate is an end product of glycolysis. The substrate is glucose
What is a substrate?
The substance on which an enzyme acts
Look up the pathway leading to pyruvate in a text book. Going from one molecule of substrate to pyruvate, how much nett ATP is generated?
2 ATP
What is substrate-level phosphorylation and what is oxidative phosphorylation?
Substrate-level phosphorylation: the formation of ATP from ADP and an phosphorylated intermediate. This is the direct method. It is quicker than oxphos, but has a lower ATP yield.
More explanation: Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP or GTP by the transfer of a phosphate group from a substrate directly to ADP or GDP. Transferring from a higher energy (whether phosphate group attached or not) into a lower energy product.
Oxidative phosphorylation: An indirect method of phosphorylation in which energy is released in ECT to generate ATP.
More explanation: Oxidative phosphorylation is the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH 2 to O 2 by a series of electron carriers. This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms
What are redox half reactions?
Either the oxidation or the reduction component of a redox reaction.
What are the redox half reaction for NAD+/NADH, O2/H2O and H+/H?
NAD+ + H+ + 2 e- NADH
O2 + 4 H+ + 4 e- 2 H2O
2 H+ + 2 e- H2
??What does the diaphorase enzyme do – which reactions does it couple?
Diaphorese is a NADH dependent enzyme/dehydrogenase. It acts as a hydrogen acceptor, meaning it transfers hydrogen ions between donor and acceptor molecules
What is meant by exergonic?
Exergonic: a chemical reaction that releases free energy in the process
What does heterotrophic mean?
A heterotroph is an organism that cannot produce its own food, instead taking nutrition from their surroundings (other sources of organic carbon, mainly plant or animal matter).
What would be the use of making lactate out of pyruvate? What happens to co-factors in this reaction?
In the process of making lactate out of pyruvate NADH + H+ will be recycled back to NAD+, which can be used for glycolysis. Fermentation occurs when oxygen is low. It generates substrates that can be used as a terminal electron acceptor
Why do the authors of article 1 conclude that LECA had a mitochondrion?
There are no differences between aerobic and anaerobic gene sets, the anaerobic eukaryotes have small differences indicating an evolutionary process of specialization to an anaerobic lifestyle distinct from the process in protists. Together with the finding that all known eukaryotic groups possess an organelle of mitochondrial origin
What kind of organelle is the glycosome?
A peroxisome. It is a membrane-bound organelle in the cytoplasm that oxidizes fatty acids and amino acids. In the reaction H2O2 is produced. The glycosome contains a major part of the glycolytic pathway
Where do the reactions of the glycosome take place in other eukaryotes?
In the cytoplasm
Where are the enzymes that function inside the glycosome synthesized?
In the cytosol. They are then imported in.
What is the role of the mitochondrial respiratory chain in the bloodstream form of T. brucei?
Converd G3P to DHAP, which will be shuttled back to the glycosome and converted to pyruvate
Consider 1 molecule of glucose entering bloodstream-form T. brucei. Consider aerobic conditions.
• How much nett ATP is generated inside the glycosome?
0 ATP (-2 ATP +2 ATP=0 ATP)
Consider 1 molecule of glucose entering bloodstream-form T. brucei. Consider aerobic conditions
Is there a redox balance inside the glycosome?
Yes.
DHAP –> G3P + 1 NAD+
GAP –> 13 BP6A + NADH
Consider 1 molecule of glucose entering bloodstream-form T. brucei. Consider anaerobic conditions.
• How much nett ATP is generated inside the glycosome?
0 ATP
Consider 1 molecule of glucose entering bloodstream-form T. brucei. Consider anaerobic conditions
Is there a redox balance inside the glycosome?
Yes. 1 NAD+, 1 NADH
Why would an inhibitor of trypanosomal alternative oxidase (AOX) not block ATP synthesis completely? With what kind of inhibitor should it be combined to block ATP synthesis?
Alternative oxidase (AOX) converts G3P to DHAP in the mitochondrion. The pyruvate branch is not blocked and generates 1 ATP. Possible targets are GAP dehydrogenase and 3PG kinase
?? Look at the table in Fig 1. What happens to the glycolytic enzymes that are in the glycosome when the parasite differentiates from the bloodstream-form into the insect stage (procyclic stage, PCF)?
It is no longer the main metabolic route. The concentration of glycolytic enzymes is reduced by pexophagy
What could be an advantage of having a glycosome?
Increased metabolic flexibility and no regulated cytosolic activation (more energy efficient)
Describe the decision tree used to classify organelles of mitochondrial origin
- Does it produce ATP? Yes –> 2., No: it is a mitosome (class 5)!
- Does it EXCLUSIVELY use O2 as the terminal electron acceptor? Yes: it is an aerobic mitochondrian (class 1), No –>3
- Does it produce H2? Yes–>4, No: it is an anaeobic mitochondrion (class 2)
- Does it possess an electron transport chain? Yes: it is a H2 producing mitochondrion (class 3), No: it is a hydrogenosome (class 4)
