Really want reference Sources for this question, either textbook or Peer Reviewe
ID: 3514470 • Letter: R
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Really want reference Sources for this question, either textbook or Peer Reviewed Journal.
During the late 1980s, HIVIAIDS patients were treated with azidothyramidine (AZT), a drug that was designed to inhibit DNA polymerase which is involved in HIV replication. However, patients were found to develop complications such as weakening heart muscle. When their muscle was stained and viewed under the microscope, ragged red fibres were observed (see image below). a) b) c) What are ragged red fibres? Explain how AZT affects mitochondria. What happens to the cell when mitochondria become damaged? In your answer make comparisons to a normal cell. What marker can be used as an indicator of mitochondrial failure and why? (2 marks) (2 marks) (2 marks) (2 marks) d)Explanation / Answer
1) When viewed under microscope, red ragged fibres and red rimmed and often have blank cracks. They also show granular degeneration and rods. This is a consequence of DNA depletion and mitochondrial myopathy.
2) ?AZT interferes with mitochondrial DNA and causes it to dysfunction. This in turn defects the beta oxidation of fatty acids. When the beta oxidation impairs, the muscle carnitine levels fall and lipid droplets accumulate in muscle. Muscle carnitine levels fall since muscle start uptaking carnitine. Muscle energy stores also deplete.
3) ?When mitochondrial machinery fails, muscles start to deplete in carnitine. (Carnitine causes transport of long chain fatty acids in muscles)
Due to absence of beta oxidation, lipid accumulates in muscles.
Muscles do not get enough energy.
In a normal muscle, energy from beta oxidation is utilised and thus lipid does not accumulate
4) Recent studies show that insulin resistance can be a marker of mitochondrial dysfunction.
Lipomata are reliable markers here, produced due to the same cause- non metabolism of fatty acids.
We are not allowed to give external links as per Chegg policy. However, I'll mention the name of a journal- you may refer to it. Research is ongoing on this subject and varying answers may be found on different sources. I am presenting you the most widely accepted probability.
You may refer the abstract of Zidovudine-inducedmitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage by DalakasMC, et al. Ann Neurol. 1994.
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