Problems related to problems related to oxidative pathway
a. Most imp: cytochrome oxidase (last enzyme before it transfers the electrons to O
Remember the 3 C’s – cytochrome oxidase, cyanide, CO all inhibit cytochrome oxidase.
Therefore 3 things for CO – (1) decrease in O sa2 (hypoxia), (2) left shifts (so, what little you
carry, you can’t release), and (3) if you were able to release it, it blocks cytochrome oxidase,
so the entire system shuts down
b. Uncoupling – ability for inner mito membrane to synthesize ATP. Inner mito membrane is
permeable to protons. You only want protons to go through a certain pore, where ATP
synthase is the base, leading to production of ATP; you don’t want random influx of protons
– and that is what uncoupling agents do. Examples: dinitrylphenol (chemical for preserving
wood), alcohol, salicylates. Uncoupling agents causes protons to go right through the
membrane; therefore you are draining all the protons, and very little ATP being made. B/c
our body is in total equilibrium with each other, rxns that produce protons increase (rxns
that make NADH and FADH, these were the protons that were delivered to the electron
transport system). Therefore any rxn that makes NADH and FADH that leads to proton
production will rev up rxns making NADH and FADH to make more protons. With increased
rate of rxns, leads to an increase in temperature; therefore, will also see HYPERTHERMIA.
Complication of salicylate toxic = hyperthermia (b/c it is an uncoupling agent). Another
example: alcoholic on hot day will lead to heat stroke b/c already have uncoupling of
oxidative phosphorylation (b/c mito are already messed up).
These are all the causes of tissue hypoxia (ischemia, Hb related, cyto oxidase block,
uncoupling agents). Absolute key things!
What happens when there is:
a. resp acidosis – Hb stays same, O s2t’n decreased, partial pressure of O decr2ased (O sat 2
decreased b/c pO is2decreased)
b. anemia – only Hb is affected (normal O sat2n and pO ) 2
c. CO/methemoglobin – Hb normal, O sat’n decreased, pO normal
Rx CO – 100% O ; 2ethemo – IV methaline blue (DOC) or vit C (ascorbic acid)
C. Decreased of ATP (as a result of tissue hypoxia)
1. Most imp: have to go into anaerobic glycolysis; end product is lactic acid (pyruvate is
converted to lactate b/c of increased NADH); need to make NAD, so that the NAD can feedback
into the glycolytic cycle to make 2 more ATP. Why do we ha