Alkaptonuria results when an individual has no functional HGD enzyme. Without functional HGD, breakdown of excess tyrosine stops at homogentisate. The accumulated homogentisate is polymerized by the enzyme polyphenol oxidase to a complex set of molecules called “ochronotic pigment” that stain the patient’s urine and tissues dark brown or black. Through an unknown mechanism, it is believed that the accumulated ochronotic pigment leads to arthritis and other symptoms of alkaptonuria.
Interestingly, none of the other intermediates in this pathway are toxic or lead to any observed disease symptoms.
The drug NTBC inhibits the enzyme 4-hydroxyphenyl pyruvate hydroxylase. NTBC has been used successfully to reduce the symptoms of alkaptonuria.
ii) In an alkaptonuria patient (one that consumes excess tyrosine) being treated with NTBC, which, if any, of the following compounds would accumulate?
4-hydroxy phenylpyruvate
4-maleyl-acetoacetate
iii) If a normal individual that consumes excess tyrosine were to take a therapeutic dose of NTBC, which, if any, of the following compounds would accumulate?
4-hydroxy phenylpyruvate
homogentisate
I believe it's a and a. Can somebody tell me for sure?
what is answer
Did you get the answer?
Ans ii)4-hydroxy phenylpyruvate iii)4-hydroxy phenylpyruvate
To determine which compounds would accumulate in an alkaptonuria patient being treated with NTBC and in a normal individual consuming excess tyrosine taking NTBC, we need to understand the metabolic pathway involved and the effect of the drug NTBC.
The metabolic pathway in question involves the breakdown of excess tyrosine. In individuals with functional HGD enzyme, excess tyrosine is broken down into several intermediates until it reaches homogentisate. Homogentisate is then further metabolized into the final products.
In alkaptonuria patients without functional HGD enzyme, breakdown of excess tyrosine stops at homogentisate. The accumulated homogentisate is then polymerized into ochronotic pigment, leading to the symptoms of the disease.
Now, let's consider the effect of NTBC. NTBC inhibits the enzyme 4-hydroxyphenyl pyruvate hydroxylase, which is responsible for the conversion of 4-hydroxyphenylpyruvate (a downstream intermediate) into homogentisate. By inhibiting this enzyme, NTBC prevents the formation of homogentisate, thereby reducing the accumulation of ochronotic pigment and alleviating the symptoms of alkaptonuria.
Now, let's answer each part of the question:
ii) In an alkaptonuria patient being treated with NTBC, which compounds would accumulate?
Since NTBC inhibits the conversion of 4-hydroxyphenylpyruvate into homogentisate, it means that 4-hydroxyphenylpyruvate would accumulate in the patient's body. Therefore, the answer is 4-hydroxyphenylpyruvate.
iii) If a normal individual consuming excess tyrosine takes a therapeutic dose of NTBC, which compounds would accumulate?
In individuals with functional HGD enzyme, excess tyrosine is metabolized into 4-hydroxyphenylpyruvate, which is then further converted into homogentisate and subsequently into the final products. However, since NTBC inhibits the conversion of 4-hydroxyphenylpyruvate into homogentisate, it means that homogentisate would accumulate in the body. Therefore, the answer is homogentisate.
In conclusion, the correct answers are:
ii) In an alkaptonuria patient (one that consumes excess tyrosine) being treated with NTBC, the compound that would accumulate is 4-hydroxyphenylpyruvate.
iii) If a normal individual that consumes excess tyrosine were to take a therapeutic dose of NTBC, the compound that would accumulate is homogentisate.