Oxidative Phosphorylation

Question 1

describe the P/O ratio

Answer 1

• P/O ratio = ratio of ATP formed per O atom reduced
• P/O ratio for NADH = 3 ATP:1 NADH oxidized by ETC
• P/O ratio for FADH₂ = 2 ATP:1 NADH oxidized by ETC
  
  • less ATP because it bypasses complex I of the ETC

Question 2

name inhibitors of the ETC

Answer 2

Question 3

ETC will be active when ___ > ____ and ____ > _____

Answer 3

ETC will be active when [ADP] > [ATP] and [NADH] > [NAD+]

Question 4

describe mt DNA and mutations

Answer 4

• mtDNA encodes 37 genes
• phenotypes are highly pleiotropic: one mutation can cause multiple phenotypes

Question 5

mitochondrial disorders are characterized by “____ ___ ___” which can be stained with ______

Answer 5

mitochondrial disorders are characterized by “ragged red fibers” which can be stained with Gomoritrichrome

Question 6

mitochondrial proliferation in muscle fibers also seen by staining for ______ ______

Answer 6

mitochondrial proliferation in muscle fibers also seen by staining for succinate dehydrogenase (complex II)

Question 7

describe Leber’s hereditary optic neuropathy

Answer 7

• defect in NADH dehydrogenase (complex 1 of ETC)
• characterized by degeneration of the retinal ganglion cells

Question 8

describe deafness induced by aminoglycoside antibiotics

Answer 8

• mutation in mitochondrial rRNA may cause predisposition to aminoglycoside toxicity causing deafness

Question 9

describe Kearns-Sayer

Answer 9

• deletion within mt DNA
  
  • most common region is 4997 bp
• affects system with higher energy requirements
  
  • paralysis of eye muscles and degeneration of retina
  • cardiac problems
  • ataxia

Question 10

describe MELAS

Answer 10

• mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
• most common mt disease
• oxdiative phosphorylation defect caused by a mutation in mt tRNA
• causes excess pyruvate to be reduced to lactic acid which accumulates in blood and other fluids

Question 11

describe MERRF

Answer 11

• myoclonic epilepsy; ragged red fibers
• most common mutation in mt tRNA gene

Question 12

what are potential treatment for patients with mt disorders?

Answer 12

• small frequent meals
• CoQ₁₀
• vit. C
• high fat diet
• carnitine

Question 13

describe artificial reproductive technology with mt disorders

Answer 13

1. healthy nucleus is extracted from mother’s defective egg
2. nucleus removed from healthy donor egg and replaced with mother’s nucleus (so donor’s mtDNA still there)
3. egg carrying genetic material of two women fertilized by male sperm and implanted