Question

1. On your internship, you visit the Mass Spectrometry Lab. Mass spectrometry can identify short peptide fragments based on their molecular weights. Your fellow intern Jerry has neglected to label his tubes of amyloid beta peptide 42 after digesting them with some proteases that we learned about in Module 6: pepsin, trypsin, and chymotrypsin. Help him figure out what protease is in each tube. Jerry’s supervisor has the fragments listed in the same order as the original peptide primary sequence, which is shown as the three-letter amino acid code, left-to-right from the free amino end (N-terminal) to the carboxyl end (C-terminal). Each fragment is listed as a separate line, in order.

Hint: see the figure and table on section 01 slide 6, we would give you the protease cleavage recognition sites on an exam. (3 marks total, 1 mark each)

Consider the sequence for the amyloid beta peptide 42, which is involved in Alzheimer’s disease:

Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Ile-Ala

Tube A:

Asp-Ala-Glu-Phe-Arg

His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys

Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys

Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Ile-Ala

Tube B:

Asp-Ala-Glu

Phe-Arg-His-Asp-Ser-Gly

Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val

Phe

Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Ile-Ala

Tube C:

Asp-Ala-Glu-Phe

Arg-His-Asp-Ser-Gly-Tyr

Glu-Val-His-His-Gln-Lys-Leu

Val-Phe

Phe

Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu

Met

Val-Gly-Gly-Val-Val-Ile-Ala

2. We express multiple types of proteases in digestion to efficiently break down proteins into short sequences, including pepsin, trypsin, and chymotrypsin.   Looking at the digestion products above, you can see that the amyloid beta peptide 42 is readily cleaved into many short sequences, making it no longer active. Many proteases are produced as proenzyme zymogens. Briefly explain why most digestive enzymes are produced as zymogens in the body, and how pancreatitis can result from cystic fibrosis (2 marks)

3. Briefly describe the biochemical basis for the following diseases. Be sure to clearly state the symptoms as well as the enzyme and metabolic pathway defect(s) involved in each: (10 marks, 2 marks each)

1. Cystinuria
2. Gout
3. PKU
4. Maple Syrup Urine Disease
5. Newborn Jaundice

Answer 1

A) Cystinuria :   

It is an autosomal recessive disorder caused  due to improper absorption of few amino acids like cysteine, lysine, arginine and ornithine.

Symptoms - nausea (vomiting sensation + giddiness) / urinary track infection / sometimes blood in urine too / formation of kidney stones.

B) Gout :

it is a medical condition caused in people with high levels of uric acid in the body .

Symptoms - Severe joint pain /inflammation of joints sometimes redness /restricted movement

.C) PKU :

It is an inherited disorder wherin the gene responsible to produce an enzyme that breaks the amino acid phenylalinine doesn’t function and hence the level of phenylalanine keeps increasing.

Symptoms : newborns usually donot show any symptoms but after few months the symptoms can be noticed. Rashes /musty odour in urine or from skin/ seizures/ psychiatric disorders/ hyperactivity / slow development/ bluish eyes.

D) Maple Syrup Urine Disease :

it is an autosomal recessive diorder affecting branched chain amino acids (isoleucine, leucine,

Symptoms : brain damage/ if left untreated death often often occurs within 5 months. In older adults symptoms like nausea/dehydration/ weight loss / lethargy (feeling tired all the time) / weight loss/ low appetite/ hypo-glycemia (low sugar) / seizures/ ketoacidosis/ pancreatitis.

E) Newborn Jaundice :

It is a condition which is caused due to excessive production of a pigment called “bilirubin” due to breakdown of red blood cells.

Symptoms : yellowish skin and eyes due to high levels of bilirubin / dark yellow to brownish coloured urine/ low appetite.