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b. The proper operation of our LDL system is critical to our LDL/HDL ratio which is...

b. The proper operation of our LDL system is critical to our LDL/HDL ratio which is a typical component of most blood tests done when you are having a physical. The ideal ratio is 3.5 to 1. In select cases, however, LDL is in very high concentrations in the blood resulting in familiar hypercholesterolemia (FH).

            i. CHALLENGE: There are a number of different genetic defects that can cause FH. You are working with a cell line from a patient with FH and need to determine if the LDL defect is due to the low number of LDL receptors present in the membrane, its ligand binding affinity or mutations (amino acid substitutions) in the NPXY sequence. How might you accomplish this task?

c. Many cancers are characterized by defects in the RTK system. What are some of these defects and why aren't defects in the LDL or ferro transferrin systems implicated in cancer?

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1)Genetic testing and LDL receptor analysis would show mutations in the LDL receptor gene, blood tests would show increased LDL cholesterol levels, and physical examinations would show skin lesions caused by cholesterol rich lipoprotein deposits

2)

One defect is the overexpression of the human epidemical growth factor receptor 2. Another defect is the disruption of microtubules by Herceptin +DA1. Defects in the LDL and ferrotransferrin systems are not implicated in cancer because they are not constantly active

These defects include a mutation RAS that is always ‘turned on’ and human epidermal growth factor receptors that cause overabundance. Also, Kadcyla is a conjugated antibody that disruptsmicrotubules. LDL and ferrotransferrin are involved with receptor mediated endocytosis and affect the heart and blood iron levels

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