biochem clinical correlations

BMR increased when all of the proton gradient energy (as opposed to just some) is transformed into heat...increases BMR

in brown adipose tissue; uncoupling protein-1 (thermogenin) is only in brown fat mit and hormonally controls non-shivering thermogenesis

thryoxine: produces less ATP and increases heat production; seen in hyperthroidism (Grave's disease)

salicylate: degradation prod of aspirin, uncouples mit oxid phosph

flavins used in oxid phosph (FMN in complex 1 and FAD in complex 2) come from riboflavin; def of riboflavin decreases mit ability to make ATP via oxid phosph

results in megamit; due to impairment of complex 1 and complex 2

(aka doxorubicin); impairs mit func by binding to complex 1

when ETC blocked, reduced complex 1 and complex 3 directly reduce molecular oxygen and end up producing superoxide radicles (toxic)

when receive a death stimuli, mit outer mem becomes permeable and releases cyt c into cytosol (act caspase cascade)

brain, heart, kidney super sens to ischemia/hypoxia bc need the most amt of ATP possible

def/prob in oxidative metab which result in accumulation of lactate in blood and incorporation of FA into triglyceride

OXPHOS disease; caused by non-func mit (muscles and nerve cells are super susceptible)

Kearns-Sayre, MERRF, LHON, MELAS

muscle weakness, exercise intolerance, heat failure, rhythm disturbances, dementia, mvmt disorders, stroke-like episodes, deafness, blindness, vomiting, seizures

muscles easily fatiqued or weakened during physical act

fish/rat poison; toxic to humans; binds to complex 1 of ETC

inhibits complex 2

inhibits complex 2

reversible inhibitor complex 4

reversible inhibitor complex 4

competitive inhibitor complex 2

uncoupler of ETC

uncoupler of ETC

binds to complex 5 and blocks mvmt through channel; fixed by adding uncouplers to leak H into the matrix