1. On Tuesday Nov. 7, 2017 Olympic marathon champion Jemima Sumgong was banned f
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1. On Tuesday Nov. 7, 2017 Olympic marathon champion Jemima Sumgong was banned from competing for four years for using a banned blood-booster drug. The drug is erythropoietin, known as EPO. EPO has been banned since the early 1990s from the Olympics because its usage is thought to significantly affect exercise performance. EPO is a glycoprotein hormone that is secreted by the kidneys and stimulates the production of red blood cells in the bone marrow. The human gene for EPO is N-glycosylated at 3 asparagine residues and O- glycosylated on a serine.. A) Why is it important for EPO to be glycosylated? B) Human EPO is a 165 amino acid protein, however EPO mature mRNA is 1340 base pairs. Provide two possible explanations for this discrepancy in length C) You are trying to express human EPO in bacteria. You succeed in making the EPO protein coding sequence express in E.coli (bacteria), but EPO is not secreted despite the fact that it was translated. Moreover, the purified protein is unable to stimulate red blood cell production and maturation. Based on your understanding of the eukaryotic secretory pathway provide a rational explanation for these observations.Explanation / Answer
Please find the answers below:
Answer A: Erythropoietin is a peptide hormone which is synthesized from the kidneys. This hormone is essential for maintain normal hemoglobin content in the blood. Like other proteins as well, erythropoietin is required to undergo post-translational modifications such as glycosylation. Thus, erythropoietin undergoes glycosylation and thenafter becomes functionalization.
Answer B: All human gene transcripts undergo post-transcriptional modification and splicing after transcription and hence undergo decrease in total base pair size. Here, the similar situation might have been encountered for the EPO transcript. Hence, although the mature mRNA might be of longer size i.e. 1340 base pairs, the final product would be much smaller in size. Here, it is important to note that three codons encode for an amino acid. Hence 1340 base pairs can encode for 1340/3 i.e. 446 amino acids. However, the product available here is smaller in nature. This could be possible only if the mRNA undergoes splicing and post-transcriptional modifications.
Answer C: Every eukaryotic polypeptide requires a leader sequence to be attached on the N-terminal of it in order to lead the nascent polypeptide to golgi apparatus or its target site. When the nascent polypeptide reaches its target site, it undergoes post-translational modifications and hence a functional protein is generated. Here, the bacterial system is lacking this leader sequence and hence the nascent protein could not be sequestered out of the endoplasmic reticulum. This is why a functional protein was not obtained inspite of obtaining positive translational product in the host.
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