In sickle-cell anemia, a base substitution in the hemoglobin gene replaces glutamate (a polar amino acid) with valine. Why does the replacement of one amino acid cause such a drastic change in biological function?

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Accepted Answer

All right. Hello everyone. So this question says that Fennel Keeton Nuria or PKU is a genetic disorder resulting from a mutation in the gene coding the enzyme phenylalanine hydroxylase. How does the mutation cause a drastic change in biological function? So, first and foremost, right, let's talk about some context to PKU as a disorder and then talk about the answer choices individually. So PKU as mentioned before is a genetic disorder from or resulting from a mutation in the gene that results in the enzyme phenylalanine hydroxylase. So, first and foremost, what does this enzyme do? And why is it important when its function is compromised? Well, based on the name, we can get an idea as to what happens to it or what it does I should say. First and foremost, based on the name, we can tell that it's going to act on the amino enzyme phenylalanine, which if you recall is a large amino acid with a benzene ring in its side chain. So phenylalanine hydroxylase implies that a hydroxy group is being added to the amino enzyme phenylalanine. And so the end result is a new amino acid where we have the same benzene ring this time with a hydroxy group. This amino acid, if you recall is tyrosine. So phenylalanine hydroxylase catalyzes the conversion of phenylalanine into tyrosine during the metabolism of amino acids. So here right, if if there's a mutation in the gene coding for phenylalanine hydroxylase, then mutations if you recall can significantly impact the structure and function of the enzyme. So if the function of phenylalanine hydroxylase is compromised, then phenylalanine cannot be converted into tyrosine. This means that pheno alanine is going to start to accumulate in the body. And phenylalanine at high levels is actually toxic to humans, which is why the symptoms of PKU begin to be observed. So with this context in mind, let's start by reading option A which says that the mutation leads to the production of a nonfunctional enzyme, preventing the conversion of phenylalanine to tyrosine. This is accurate, right. If the mutation leads to a nonfunctional gene, that's going to code for a nonfunctional version of phenylalanine hydroxylase, meaning that the conversion of phenylalanine into tyrosine cannot be done. So A is correct, but for the sake of completeness, let's talk about the other choices. Option B says that the mutation increases phenylalanine hydroxylase activity leading to excessive phenylalanine conversion. This is incorrect, right? Because an increase in phenylalanine hydroxylase activity would prevent the accumulation of phenylalanine that is toxic to humans, right. Thereby resulting in the symptoms of PKU. Option C says that the mutation enhances the binding affinity of phenylalanine to the enzyme causing it to function more efficiently, which is not true, right? Because an increase in enzyme efficiency would to an extent prevent the symptoms of PKU. And lastly, option D says the the mutation results in an enzyme with a broader substrate specificity affecting the metabolism of various amino acids. Now, the reason why D is not correct either is because this mutation that's being described here is not directly related to PKU specifically. So there you have it, right? Just to reiterate our correct answer is option A in the multiple choice. And so with that being said, thank you so very much for watching and I hope you found this helpful.

In sickle-cell anemia, a base substitution in the hemoglobin gene replaces glutamate (a polar amino acid) with valine. Why does the replacement of one amino acid cause such a drastic change in biological function?

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Key Concepts

Amino Acids and Their Properties

Protein Structure and Function

Sickle-Cell Anemia Pathophysiology