Lecture 5 - Bioenergetics and TCA cycle? Flashcards
What is the distinction between deltaG* and deltaG?
DeltaG* calculated w/ 1M products and reactant, deltaG at actual concentrations
What does a Keq greater than 1 indicate?
Products favored
What does a Keq smaller than 1 indicate?
Reactants favored
What does a negative deltaG indicate?
Products favored
What does a positive deltaG indicate?
Reactants favored
Where does beta oxidation occur?
Mitochondrial matrix
Where does TCA cycle occur?
Mitochondrial matrix
State the enzymes of the TCA starting with the enzyme that acts on Acetyl-CoA.
Citrate synthase > Aconitase > Aconitase > Isocitrate dehydrogenase > alpha-ketoglutarate dehydrogenase > succinyl-CoA synthetase > succinate dehydrogenase > fumarase > malate dehydrogenase
(CS A A ID alphaKD S SD F MD)
What regulates isocitrate dehydrogenase?
(+)Ca2+, (+)ADP (allosteric), (-)NADH
What regulates alpha-ketoglutarate dehydrogenase complex?
(+)Ca2+, (+)NADH, (-)Succinyl-CoA (product of alpha-ketoglutarate)
What regulates malate dehydrogenase?
(-)NADH
State the input and outputs into 1 cycle of the TCA loop.
INPUT: 2-carbon unit (Acetyl-CoA)
OUTPUT: 2 CO2, 1GTP, 8 high energy e-
What enzyme converts pyruvate to acetyl-coA?
Pyruvate dehydrogenase complex (PDH)
How many carbons make up pyruvate?
3
How many carbons make up acetyl-coA?
2
What are the outputs of the oxidation of pyruvate?
Acetyl-CoA, CO2, NADH (per pyruvate molecule)
What is the general enzymatic set-up of the alpha-keto acid family enzymes?
Highly integrated set of three units:
E1 - Thiamine pyrophosphate (TPP), E2 - Lip-S-S, E3 - FAD
What is the significance of arsenite relative to alpha-leto acid enzymes?
binds S-S of Lipoate and inactivates enzyme.
How is PDH (or PDC) regulated?
Phosphorylation INACTIVATES
Dephosporylation ACTIVATES
Activation: Phosphatase (Ca2+ activated)
Inactivation: Kinase (ADP & Pyruvate inhibit, Ac-CoA & NADH activate)
What is added to NAD+ by ID and alpha-KD?
Hydride ion (2 e- and proton)
Where does substrate level phosphorylation occur in the TCA cycle?
Succyinyl CoA Synthetase (Succinate thiokinase)
Dry beriberi
low B1 + peripheral neuropathy, impaired reflex functions
Wet beriberi
low B1 + cardiovascular disease
How to chronic alcohol abuse cause thiamine deficiency?
Ethanol inhibits thiamine intake + alcohol abuse often accompanied by poor nutrition
What inhibits function of citrate synthase?
Citrate - it’s own product, negative feedback
How many ATP/cycle?
1 GTP + 3 NADH + 1 FADH2 = 10ATP/cycle
Explain why anaplerotic pathways are necessary.
Intermediates in the TCA cycle may be used for biosynthetic reactions and thus deplete a given intermediate. Anaplerotic pathways allows intermediates to be “re-filled” or replenished.
List the three anaplerotic pathways contained within the notes.
1) Substrate: pyruvate, Enzyme: pyruvate carboxylase, Intermediate: oxaloacetate
2) Substrate: Glutamate, Enzyme: Glutamate dehydrogenase + transaminase, Intermediate alpha-ketglutarate
3) Substrate: Odd # FAs, valine, & isoleucine > propionyl CoA then enter as intermediate: Succinyl CoA