Oxidative Phosphorylation

Describe the steps of Oxidative phosphorylation, Name the complexes

1. NADH —> NAD + at COMPLEX 1 (NADH:CoQ Reductase); 4H+ pumped

2. CoQ now has the electron and go to COMPLEX III (Cytochrome v-c1 complex); 4H+ pumped

3. Cytochrom C now has the electron

4. Goes towards COMPLEX 1V (cytochrome oxiase); 2H+ pumped; 2O2 + 4e- = 2 H2O

NOTE: complex II = succinate dehydrogenase an ETF:Q oxidoreductase. FADH goes here but NO H+ IS PUMPED

What are chemical uncouplers? What is it also known as? What is the consequences of this

• AKA proton ionophores are lipi soluble compounds

• able to transport H+ from cytosolic side to matrix

• this dissipates the electrochemical potential gradient

• = mitochondria can’t make ATP; mitochondria lost integrety and function

What is DNP? Describe how it is problematic? Toxicities of these products = what symptoms? Describe the mechanism of this?

• 2,4 Dinitrophenol is a lipid soluble ionophore

• problematic because can transport protons from intermembrane space to the matrix = heat

• symptoms: tachycardia, tachypnea (rapid shallow breath), diaphoresis (sweating) and death

• mechanism: high [H+] = proton binding to DNP in intermembrane space; low [H+] = proton dissociating from DNP into matrix

What do UCPRs Do? What do UCP1 do in the body?

UCPRs form pores through the inner mitochondrial membrane; causing proton to go down its concentration gradient

UCP1 = Thermogenin = association of heat production in brown adipose tissue

• What is brown adipose tissue’s function? What is white adipose tissue’s function? Why is brown adipose brown? How does epinepherine relate to brown adipose tissue? Why do infants have brown fat?

brown adipose tissue = generate nonshivering heat

white adipose tissue = store fat as triglycerie

brown because lots of mitochondria

when cold or low in food —> Epinepherine activates hormone-sensitive Lipase —> cleaves FA —> these cause CoQ to be reduced for ATP synthesis and UCP1 to be activated, returning protons back to the matrix = heat production

Infants have brown fat because to insulate them from cold (have no control over their environment, noobs)

What is the function of amytal? What complex does it target?

amytal = sedative and hypnotic; complex 1

What is the function of rotenone? What complex does it target?

inset control in gardens and on pets; complex 1

What is the function of antimycin A? What complex does it target?

fungicie; complex 2

What complexes does CO and CN- disable?

complex IV

What does oligomycin do? What can this lead to?

• binds to ATP synthase and blocks H+ channel

• metabolic acidosis due to accumulation of lactate in blood

• ETC and phosphorylation = tightly coupled; inhibition of one leads to the other

what is fatal infantile mitochondrial myopathy?

ecreases in the synthesis of proteins involved in complex 1,3,4,5;

progressive liver failure and neurologic abnormalties, hypoglycemia and increased lactate in body fluids

what does defieciency in NADH:Ubiquinone oxidoreductase lead to?

leads to mitochondrial encephalopathy, lactic acidosis, and stroke (MELAS) disorder

What is LHON?

Leber’s hereditary optic neuropathy results from point mutation in MTDNA for gene coding for NADH dehydrogenase or NADH:ubiquinone oxidoreductase; patients with this disease develop loss of central vision in 20s to 30s

what is Kearn-Sayre syndrom

mutations in mtDNA lead to defect in complex II;

symptoms: short stature, complete external opthalmoplegia, pigmentary retinopathy, ataxia, and cardiac conduction defects

what is leigh disease

mtDNA disorder; leads to lactic acidmia, developmental delay, seizure, extraocular palsies, hypotonia and death by 2

what does overconsumption of alcohol and certain drugs do?

expression of various cytochrome mono-oxidases; these form reactive oxygen species from the P450