TCA Cycle DR. A

Question 1

How does the pyruvate get into the midocondria?

Answer 1

Through the mitochondrial pyruvate

carrier (MPC)

Question 2

Explain regulation on the Pyruvate dehyrodgenate complex.

Answer 2

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

Question 3

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

Answer 3

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

Question 4

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

High?

Answer 4

Low levels Increase activity

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

Question 5

What are Anaplerotic reactions?

Answer 5

Replenish the intermediates of TCA cycle

Question 6

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

Answer 6

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

Question 7

How can Succinyl Co A be redirected?

Answer 7

Prophorins go to Heme

Question 8

What are the symptoms of 2-Oxoglutaric aciduria?

Answer 8

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

Question 9

What is fumerase deficiency caused by?

Characteristics?

Answer 9

-Autosomal recessive
disorder
-Mutation in fumarase
gene contains Q319E

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

Question 10

What is the recently discovered disorder?

What is it caused by?

Answer 10

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

Question 11

How does mitocondrial depletion syndrome deficency manifest?

Answer 11

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

Question 12

How is E’ defined as?

Answer 12

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

Question 13

How is Standard redox potential related to standard free energy?

Answer 13

delta G’ = -nFdeltaE’ inversely related

Question 14

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

Answer 14

pH gradient, membrane potential

Question 15

What blocks the ATP synthase (complex 5)?

Answer 15

Oligomycin inhibitor

Question 16

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

Answer 16

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

Question 17

What happens when you change the proton gradient?

Answer 17

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

Question 18

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

Answer 18

Brown adipose tissue

Question 19

How does reduced NADH enter the mitocondrial matrix?

Answer 19

Through the Malate aspartate shuttle

and the Glycerophosphate shuttle

Question 20

Where does Malate aspartate shuttle occur?

What is the product and where does it enter? ETC?

Answer 20

Heart, liver, kidneys (COMPLEX I)

Question 21

Where does the Glycerophosphate shuttle occur?

What is the product and where does it enter the ETC?

Answer 21

Skeletal Muscle and brain, 
generates FADH (Complex II)

Question 22

What are the two primary causes of mitochondrial disease?

Answer 22

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

Question 23

What are some other causes of mitochondrial disease?

Answer 23

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

Question 24

What are the clinical manifestations of mitochondrial disease manifested?

Answer 24

– 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.

Question 25

What are the metabolic features of mitochondrial diesases?

Answer 25

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

Question 26

What 4 things were learned by isolating straited muscle mitochondria?

Answer 26

– 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