Biochemistry 1: TCA cycle & ETC (11 main concepts) Flashcards
Why does your skin get bright red with cyanide poisoning?
Cyanide binds to complex IV in electron transport chain → shuts down → O2 not consumed by ETC as final electron-acceptor → stays bound to hemoglobin → venous blood more oxygenated → bright red skin
Cyanide poisoning – treatment? Why?
2 steps:
1. Oxidizing agent (amyl nitrite): Hemoglobin (Fe2+) → methemoglobin (Fe3+); yes, you actually TRY to generate methemoglobin, which is itself pathogenic, but in this case, useful, since CN- binds more effectively to Fe3+ than Fe2+
2. Thiosulfate + cyanide → thiocyanate → excreted in urine
Cyanide poisoning – would lactic acid levels be higher or lower? Why?
Lactic acid. Recall that the electron transport would be shut down → reliance on anaerobic glycolysis. Lactic acid produced to turn NADH → NAD+, so it can be used in glycolysis to generate a small amount of ATP (2 net ATP per glucose).
NOTE: you MUST understand why lactic acid is produced, as this is a very common molecule that shows up on tests very often
Cyanide poisoning – why are we “triple screwed”?
- Oxygen displaced by cyanide on hemoglobin
2. Oxygen bound more tightly to Hgb and can’t be released
3. If oxygen is released, it can’t be used for OxPhos
How many carbons does citrate have? How can you make sense of this based on its precursor molecules?
Citrate = 6 carbons. Acetyl-CoA has 2 carbons (made from the 3-carbon pyruvate via dehydrogenase enzyme that eliminates CO2 from pyruvate) + oxaloacetate has 4 carbons.
What is the point of the electronic transport chain? How does it accomplish this?
Generate ATP (much more efficient than glycolysis).
Movement of electrons donated from NADH and FADH2 (from TCA cycle) → protons pumped into the intermembranous space, against its gradient. Movement of H+ down its gradient, through ATP synthase, drives ATP production
Walk through the electron transport chain. What is the end result?
As electrons from NADH and FADH2 move through the electron transport chain, H+ move from the inner mitochondrial matrix to the intermembrane space → H+ moves down its chemical gradient to drive production of ATP
End result = ATP production (with O2 consumed as the final electron acceptor)
What is methemoglobin, and what problem does it cause?
The iron (Fe) atom within hemoglobin is usually in the 2+ state. Methemoglobin has Fe3+, and does not bind O2 well → tissue hypoxia if levels high enough
Why might someone actually try and abuse 2,4-DNP?
Recall that the ETC uses the electrons from NADH/FADH2 generated by the TCA cycle to pump protons into the inter membranous space in the mitochondria. The energy from the electrochemical gradient generated in this process is used to generate ATP.
2,4-DNP is an uncoupler, and destroys the H+ (proton) gradient, by moving the protons from the inter membranous space back INTO the mitochondria. Instead of the energy of the gradient being used for ATP generation, it will simply be dissipated as heat.
Uncouplers cause weight loss, because instead of efficiently generating ATP from NADH/FADH2, you “waste” their energy. This causes weight loss.
Walk through the electron transport chain. How would 2,4 DNP affect it?
As electrons from NADH and FADH2 move through the electron transport chain, H+ move from the inner mitochondrial matrix to the intermembrane space. Normally, these H+ ions would drive the production of ATP. However, 2,4-DNP destroys the H+ gradient by shuttling the H+ back into the mitochondrial matrix → ATP production ↓.
What is the purpose of brown fat? How does it work?
Brown fat is found in (predominantly) babies. It contains thermogenin, which, like 2,4-DNP is also an uncoupler. As the name “thermogenin” (thermo = heat, genin = generator) implies, uncoupling the ETC increases heat generated – this is why baby’s have brown fat.
