Lecture 4: Mitochondrial Bioenergetics Flashcards
What is substrate level phosphorylation? What are some examples?
Direct transfer of a phosphate group to ADP or GDP
PEP –> Pyruvate
Phosphocreatine –> Creatine (MI marker)
What is oxidative phosphorylation?
ATP formation as a result of the transfer of electrons from NADH or FADH 2 to oxygen by a series of electron carriers
What are amphibolic reactions?
Anabolic (making bigger things) and catabolic (breaking down things)
Where does the TCA cycle take place?
Mitochondrial matrix
How does pyruvate enter mitochondria?
Mitochondrial Pyruvate Carrier (MPC)
What downregulates pyruvate dehydrogenase complex (PDC)?
NADH, ATP, Acetyl-CoA
Which three steps of the TCA cycle are irreversible and regulatory? What enzymes catalyze them?
Step 1: Citrate Synthase
Step 3: Isocitrate dehydrogenase (rate limiting)
Step 4: α-Ketoglutarate Dehydrogenase
What are the four products of the TCA cycle?
1 FADH2
3 NADH
1 GTP
2 CO2
What enzyme can hijack the TCA cycle from the start, and what inhibits it to allow the TCA cycle to continue?
Pyruvate Carboxylase (pyruvate –> oxaloacetate). Oxaloacetate will then enter gluconeogenesis
Insulin inhibits Pyruvate Carboxylase
What TCA intermediate can be shunted off to make porphyrins like heme?
Succinyl CoA
What are the clinical effects of phosphatase deficiency?
Lactic Acidosis
When PDC is phosphorylated, it is inactive. Pyruvate Dehydrogenase Phosphatase activates PDC.
When PDC is not activated, pyruvate will produce lactate instead of Acetyl Co-A.
At what part of Pyruvate Dehydrogenase Complex do low energy compunds push the reaction forward?
At Pyruvate Kinase
Low energy compounds STOP pyruvate kinase from phosphorylating Pyruvate Dehydrogenase
Goal: Keep PDC activated (dephosphorylated)
What 4 TCA enzymes produce reducing power?
isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase
succinate dehydrogenase
malate dehydrogenase
Which TCA cycle enzyme produces FADH2?
Succinate Dehydrogenase
What is 2-oxoglutaric aciduria?
Rare disorder with severe neurological and developmental problems in infants
- metabolic acidosis
- severe microcephaly
- mental reatrdation
What is fumarase deficiency?
Severe neurologic impairment and infant fatality
What is Succinyl-CoA syntetase deficiency?
Mutations in enzyme: SUCLA2 and SUCLG1
What happens in mitochondrial depletion syndrome?
Profound hypotonia
Progressive dystonia
Muscular Atrophy
Hearing impairment
Where does oxidative phosphorylation occur?
Inner mitochondrial membrane
What is mitochondrial fission?
Mitochondria divides to make 2 sister mitochondria
What is mitochondrial fusion?
2 mitochondria fuse to make one
Does an agent with a lower Eo’ have a higher or lower affinity for electrons?
Eo’ being low means its affinity for electrons is low.
-Normally will be reducing agent (is oxidized)
What compounds inhibit Complex 1?
Amytal
Rotenone
Myxothiazol
Piericidin A
What compound inhibits complex II?
Malonate
