Mitochondrial

Question 1

What are the products of anaerobic respiration?

Answer 1

Glucose is broken down into pyruvate, ATP, and NADH

Question 2

What happens to pyruvate with and without oxygen?

Answer 2

No oxygen - then pyruvate is converted to lactate (in cytoplasm)

Oxygen - transported to mitochondria where pyruvate dehydrogenase converts it into Acetyl-CoA for use in the TCA cycle

Question 3

What could elevations in pyruvate, lactate, and alanine during times of sufficient oxygen supply indicate?

Answer 3

dysfunction of either the Krebs cycle or Electron Transport Chain

Question 4

What is heteroplasmy?

Answer 4

the presence of more than one type of mitochondrial DNA in an individual; variable ratios of normal to mutant mtDNA in each cell

Question 5

Point mutation in mtDNA at 8993 is responsible for what spectrum of mitochondrial disease?

Answer 5

Kearns-Sayre Syndrome 80% mutation

severity of disease increases with mutation percentage

Question 6

What is a biproduct of protein catabolism?

Answer 6

Ammonia

ETC dysfunction can cause ammonia levels to elevate very quickly

Question 7

CoEnzymeQ is the product of which complex(es) in electron transport chain?

Answer 7

Complex I and Complex II

accepts electrons from these complexes and transports them to Complex III

Question 8

Which organs are most affected by mito disorders?

Answer 8

Organs that require the most energy:

CNS, eye, hearing, cardiac, GI, renal, endocrine/diabetes, peripheral nervous system

Question 9

What are the symptoms of Leigh Syndrome?

Answer 9

early childhood onset, hypotonia, spasticity, peripheral neuropathy, brainstem & basal ganglia degeneration, visual loss, exacerbation with intercurrent infections, usually fatal in infancy

Question 10

Common mtDNA mutation: A1555G

Answer 10

Associated with aminoglycoside-associated deafness, non-syndromic deafness and maternally-inherited cardiomyopathy.

Question 11

Common mtDNA mutation: A3243G

Answer 11

MELAS, but far more than just that– a wide variety of neuromuscular, endocrine, and renal tubular diseases have been reported. The most common phenotype is diabetes (estimated 1% of all diabetes is due to this mutation). Migraine and deafness are also common with this mutation.

Question 12

Common mtDNA mutation: A8344G

Answer 12

Common MERRF mutation

Question 13

Common mtDNA mutation: T8993G/C

Answer 13

Moderate levels of heteroplasmy cause NARP, higher levels cause Leigh disease

Question 14

Pearson syndrome

Answer 14

Infantile refractory sideroblastic anemia (with variable other blood cell anomalies) and exocrine pancreatic dysfunction. Usually caused by large mtDNA deletion/duplications. KSS can occur in survivors.

Question 15

NARP

Question 16

MNGIE

Question 17

MERRF

Question 18

LHON

Question 19

Leigh disease

Question 20

Barth syndrome

Answer 20

X-linked cardiomyopathy, skeletal myopathy and cyclic neutropenia. The gene (tafazzin) was recently identified.

Question 21

KSS

Question 22

MELAS

Answer 22

Myopathy, mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes; may present only as diabetes mellitus and deafness

Most common mutation: tRNA leu UUR; 3243A>G

Question 23

Mitochondrial deafness

Answer 23

progressive sensorineural deafness, often induced by aminoglycoside antibiotics; nonsyndromic sensorineural deafness