TCA and Mitochondria Flashcards
(43 cards)
What are some of the key features of the mitochondria?
- Outer membrane is permeable to most molecules under 6kda
- Inner membrane is VERY IMPERMEABLE, contains cardiolipin almost no cholesterol
- allows voltage and proton concentration gradients to be established, generated using ATP
What does mitochondrial DNA do? How does it effect proteins in the mitochondria?
- Mitochondria have own small genome, machinery for transcription and translation
- Encodes a few proteins of the ETC, and tRNAs used in translation of mitochondrial genes, but most come from nuclear DNA and are delivered there
- Reproduce by fission, inherited maternally
Why is mtDNA hypermutable?
- naked, not bound to histones in chromatine structure
- exposed to high concentrations of reactive oxygen species (ROS), damage increases with age
- Genome has limited ability to repair DNA damage
How does mtDNA over come hypermutability?
- Multiple mitochondria in each cell
- Multiple copies of mtDNA in each mitochondria
How are mt diseases heterogenous?
- Normal and mutant DNA can be present in the same person/cell at diff ratios
- Results in a RANGE of phenotypes for diseases caused by mutations in mt genes
- diseases tend to be progressive, get worse with age
What is the role of Pyuvate dehydrogenase?
Links Glycolysis to the TCA cycle, defects in PDH lead to seroius neurological conditions.
Where are glycolysis, PDH and the TCA cycle in a cell?
Cytosol- glycolysis
Mitochondria- PDH and TCA
What protein transports pyruvate into the mitochondria? What happens if it inherits point mutations?
- MPC (MItochondrial pyruvate carrier
- mutations cause lactic acidosis and hyperpyruvatemia
How many subunits does PDH have and what do they do?
4 subunits
E1- pyruvate decarboxylase (TPP)
E2- Transacetylase (lipoate)
E3- Dihydrolipoyl dehydrogenase (FAD,NAD+)
How is PDH regulated?
-Activated: acetyl CoA, NADH
Phhosphorylation of E1 turns off PDH, swicth to FA metabolism
-Deactivated: Pyruvate and ATP, dephosphorylation of E1 turns on PD
What does PDH phosphatase do?
Has reverse effect on PDH kinase and activates E1, activated by Ca
What are the sources of acetyl coA?
Fatty acids, ketone bodies, glucose, pyruvate, ethanol
What is the key rate limiting enzyme in the TCA cycle?
Isocitrate dehydrogenase
What are the two energetically unfavorable (positive G) reactions?
- Citrate to Isocitrate (reverse favorable)
2. Malate to oxaloacetate (“”)
What does succinate dehydrogenase do?
Oxidizes succinate to introduce double cc bond, reducing FAD and creating fumarate
- SD is a component of the ETC, creates proton gradient for generation of ATP
- Tumor supressor gene, causes mutations in enzyme that generates fumerate, increase conc of fumerate which out competes ketogluterate
How many ATP are created during the TCA cycle?
10 ATP
2 carbon acetyl groups and 2 waters, create 2 CO2
What happens to NAD and NADH when energy is consumed?
What effect does this have on oxaloacetate?
What effect does this have on isocitrate?
NAD increases (moves rxn forward), NADH decreases
Oxaloacetate increases
Isocitrate decreases
What happens when energy is abundant?
What effect does this have on malate? Isocitrate? Citrate?
Nad+ decreases, NADH increases
Malate- increase, isocitrate–won’t change much (hump), citrate–increases
What does ethanol metabolism do?
Produces NADH.
In alcohol poisoning massive amount of NADH produced locks up TCA cycle.
What regulates isocitrate dehydrogenase?
Ratio of ADP to ATP in mitochondria. (allosteric)
Activator-ADP, indicates e shortage, increase TCA cyle to make more FAD, more e
Inhibitor-ATP, NADH
How is the TCA cycle amphibolic?
It is catabolic and anabolic
Catabolic- TCA reduces NAD and FAD for generation of ATP in ETC
Anabolic- TCA intermediates are feedstock for biosynthetic pathways
What are TCA intermediates? What type of biosynthesis do they promote?
Malate--> glucose Oxaloacetate--> AA Citrate--> FA alphaketoglutamate --> glutamate--> GABA Odd chain fatty acids--> succinyl coA--> heme biosynthesis
How does the TCA cycle replace intermediates that leave for other pathways?
- Pyruvate carboxylase–converts pyruvate to oxaloacetate
- Pyruvate–From AA or Carbs
- Glutamate- deaminated to make a ketoglutarate
- Branched chain AA converted to propionyl coA, then succinyl CoA
- Direct transamination of aspartate to malate
When exercising, the amount of oxaloacetate can be a limiting factor for the production of E through the TCA cycle. What pathway supplies oxaloacetate to TCA cycle?
Use ATP to “recharge the batteries”
