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Flashcards in TCA Cycle DR. A Deck (26):

How does the pyruvate get into the midocondria?

Through the mitochondrial pyruvate
carrier (MPC)


Explain regulation on the Pyruvate dehyrodgenate complex.

Always phosphorylated and inactive by the PDK (Pyruvate dehyrodgenase kinase)
Dephosphorylated by the PDP


If have a phosphotase deficiency what are the effects on the body?

The PDC is then always phosphorylated and inactive causing pyruvate to be turned into lactate ---> lactic acidosis


If have low levels of ATP what does this do the TCA?

Low levels Increase activity
HIgh levels decrease activity through mechanism of TCA cycle ->mitochondrial ETC inhibition


What are Anaplerotic reactions?

Replenish the intermediates of TCA cycle


What AA's can be added and where to the TCA?

Alpha ketoglutarate: Glutamate, Gluatamine, Proline, Histamine, Arginine
Succinyl CoA: Propinyl Co A, Isoleucine, methionine, threonine, valine
Fumerate: Aspartate, Phenylaine, Tyrosine
Oxaloacetate: Asparagine, Asparate


How can Succinyl Co A be redirected?

Prophorins go to Heme


What are the symptoms of 2-Oxoglutaric aciduria?

A rare disorder with global developmental delay and
severe neurological problems in infants
- Metabolic acidosis
- Severe microcephaly
- Mental retardation


What is fumerase deficiency caused by?


-Autosomal recessive
-Mutation in fumarase
gene contains Q319E

Characterized by severe neurological impairment.
Fatal outcome within the first 2 yrs. of life
-Increased urinary excretion of fumarate, succinate, aketoglutarate, and citrate


What is the recently discovered disorder?
What is it caused by?

Succinyl-CoA synthetase (SCS)
Caused by mutations in SUCLA2 and SUCLG1
encode B subsunit of SCS


How does mitocondrial depletion syndrome deficency manifest?

Profound hypotonia
- Progressive dystonia
- Muscular atrophy
- Severe sensory neural
hearing impairment


How is E' defined as?

Standard redox potential measures affinity for electrons
Lower the Redox potential less it wants electrons, i.e.
High Redox potential takes the e- you do not want the electrons


How is Standard redox potential related to standard free energy?

delta G' = -nFdeltaE' inversely related


What are the two factors that contribute to the proton motive force?

pH gradient, membrane potential


What blocks the ATP synthase (complex 5)?

Oligomycin inhibitor


What happens when the flow of e- along ETC is inhibited? (3`)

-A decrease in the
pumping protons
-A decrease in the
protein gradient
-Inhibition of ATP


What happens when you change the proton gradient?

H+ ions that were pumped will flow back into mit. matrix and you will generate heat, but NO ATP


In what type of tissue is there uncoupling of oxidative phosphorylation?

Brown adipose tissue


How does reduced NADH enter the mitocondrial matrix?

Through the Malate aspartate shuttle
and the Glycerophosphate shuttle


Where does Malate aspartate shuttle occur?
What is the product and where does it enter? ETC?

Heart, liver, kidneys (COMPLEX I)


Where does the Glycerophosphate shuttle occur?
What is the product and where does it enter the ETC?

Skeletal Muscle and brain,
generates FADH (Complex II)


What are the two primary causes of mitochondrial disease?

–Defect in nuclear DNA (nDNA) encoding the mitochondrial proteins
– Defect in mitochondrial DNA (mDNA)


What are some other causes of mitochondrial disease?

– Ischemia
– Reperfusion
– Cardiovascular diseases
– Renal failure
– Drugs and aging
– Alcohol
– Smoking.


What are the clinical manifestations of mitochondrial disease manifested?

– Nervous system: seizures,ataxia,dementia, deafness, blindness
– Eyes : ptosis, external ophtalmolplegia,retinis pigmentosa with visual loss
– Skeletal muscle : Muscle weakness, fatigue, myopathy, exercise
intolerance, loss of coordination and balance
– Heart: cardiomyopathy
– Others: gastrointestinal, liver failure, kidneys, pancreatic disease,
diabetes, etc.


What are the metabolic features of mitochondrial diesases?

– Low energy production
– Increased free radical production
– Lactic acidosis


What 4 things were learned by isolating straited muscle mitochondria?

– Uncoupling of oxidative phosphorylation was found
– High levels of Cytochrome-c oxidase
– Relatively low levels of coenzyme Q10
– High content of RNA in muscle homogenate (evidence of mito-protein synthesis