Denaturing and Protein Function: Teacher Instructions

Teacher: Sue Lighthall; James Madison High School; San Antonio, TX
Research Host: Dr. Andrew Tsin; The University of Texas at San Antonio
Frontiers Summer Research Program 1996

Purpose
To provide students with an opportunity to apply their basic understanding of proteins to a problem involving the hydrolysis of a compound.

Objectives
1) Improve students' skills in experimental design and analyzing data.
2) Gain skills in using a colorimeter as a tool to measure the hydrolysis of a compound.

Materials (for groups of two)

Procedure
Students should be familiar with the structure of proteins and how they can be denatured. A pre-lab activity might include cooking an egg and having students describe what they observe. Afterward, talk about how proteins can be denatured by heat or change in pH.

Background information should also include how proteins function as enzymes. The students should be aware that enzymes function as catalysts and are specifically structured to perform a certain chemical reaction. The natural function of esterase, which is the enzyme used in this lab to hydrolyze pNPP, is to hydrolyze esters in the liver. Esterase is found in the membranes of the liver cells like the endoplasmic reticulum. When the liver encounters substances that the body cannot tolerate, it turns them into esters. The esters are then hydrolyzed by the esterase and can be removed from the body easily.

If students have never used a colorimeter, describe how it measures the amount of light passing through the mixture being tested. It will give the absorbance of light over the amount of time. In this lab it will record the change of absorbance of the pNPP as it is hydrolyzed by the esterase. The more pNPP is hydrolyzed, the darker yellow the solution will become.

The students must design an experiment to prove that esterase will hydrolyze pNPP, changing it from clear to yellow using only the materials available. Also they should prove that temperature and pH change will denature the esterase.

Preparation
Colorimeters can be purchased from: Vernier Software, 2920 S.W., 89th St., Portland, OR 97225, Phone: (503) 297-5317. Colorimeters cost approximately $99.00. The program used to run the colorimeter and the interface box can also be purchased, as well; the program is called "Data Logger."

The liver homogenate can be prepared several months in advance. It should be prepared from fresh liver and then frozen until ready to use. Slice about 100-200g of liver into small pieces. Keep the liver cold at all times or the enzyme may become inactive. Place the liver in a blender with one liter of distilled water. Blend it until no pieces are visible. Next, centrifuge small amounts of the homogenate at 2000-5000 rpms for 10 minutes and extract the liquid. Any solid liver may be thrown away. To prepare a "boiled" liver extract, follow the same steps then boil the extract.

p-Nitrophenyl phosphate can be purchased from Sigma. Dissolve as directed (usually one tablet in 20 ml of methanol).

The esterase buffer is prepared in three steps:
1) Prepare Solution A by placing 130ml distilled water in a 250ml flask and adding 0.7g 20mM Potassium Phosphate Dibasic.
2) Prepare Solution B by placing 130ml distilled water in a 250ml flask and adding 0.54g Potassium Phosphate monobasic (q.s. to 150 ml).
3) Prepare Solution C by pHing Solution A with Solution B to 7.4pH. Into another flask, add 0.2g Trition X-100. Pour Solution C into flask with the Trition. Add 0.074g EDTA then q.s. solution to 200 ml. This can be stored at 4oC for several months.

Prepare the other buffers using purchased buffer pellets. Fischer Scientific or Sigma Chemical are good sources.

Safety
Follow standard safety procedures for laboratory experiments (e.g., goggles, lab coats or aprons, etc.). Students should be warned to be careful when using acids, bases, and chemicals (including pNPP) that can irritate their skin if they come in contact with them. If they should spill some they should rinse throughly with water.

Questions to Ask
What is the purpose of proteins? How do enzymes function? What do you expect the liver and the boiled liver to do to the pNPP? What do you expect the different pH buffers to do to the esterase?

Suggestions for Assessment
The following can be used as assessment tools: 1) Student experimental design, computer data, and laboratory reports; and 2) Oral presentation of results and experimental design.

References and Resources
Acknowledgments to Nathan Mata and Carol Leibl for information used in this lesson.

Where To Go From Here
Students could do protein gels. For example they could take hemoglobin and mix it with detergents such as Era or Wisk that contain enzymes. Then run these proteins on an agarose gel to see if Era or Wisk had the enzymes necessary to break down hemoglobin.


Denaturing and Protein Function: Student Activity
Teacher: Sue Lighthall; James Madison High School; San Antonio, TX
Research Host: Dr. Andrew Tsin; The University of Texas at San Antonio
Frontiers Summer Research Program 1996

Background
Proteins are organic macromolecules composed of smaller subunits called amino acids. The number, type, and arrangement of the amino acids determine the shape of the protein which directly controls the protein's function. The shape and function of a protein can be altered by a process known as denaturing. Too high a temperature or change of pH can cause the denaturing to take place. If this happens, then the protein can be rendered useless, unable to perform it's normal job.

There are several functions which proteins can perform. They can be part of an organism's structure. They can be used like hemoglobin in O2 transportation or used as hormones such as insulin or growth hormone. Finally, they can be used as catalyst to speed up chemical reactions in the form of enzymes. It is this last function which will be explored in this lab exercise.

Esterase is an enzyme found in the liver of many animals including humans and cows. The natural function of esterase is to hydrolyze (break down) esters in the liver. It is found in the membranes of the liver cells, such as the endoplasmic reticulum. When the liver handles toxins that the body can not tolerate and turns them into esters, the esters are then hydrolyzed by the esterase enzyme and can be removed from the body easily.

Esterase will also hydrolyze a substance called p-Nitrophenyl phosphate (pNPP). When this happens the pNPP will change from clear to yellow. The more pNPP is hydrolyzed the darker yellow it will become. This change in color can be measured by the absorbance spectra of a colorimeter.

Problem
Design an experiment using the materials available and a colorimeter. The experiment should prove that cow's liver has esterase which will hydrolyze pNPP, changing it's color and therefore it's absorbance. Also, prove that extreme temperature or pH will denature the esterase.

Materials

  • Computer
  • Colorimeter
  • 5 ml Liver homogenate
  • Ice
  • 5ml Boiled liver
  • 10ul-1000ul Pipettors
  • 500ul pNPP
  • 2ml Esterase buffer pH 7.4
  • 2ml Buffer pH 9
  • 2ml Buffer pH 4
  • 6 Cuvettes

Helpful Hints
1. Always have a source of liver, a buffer and the pNPP for every test.
2. Use 1000ul of buffer, 10ul of liver homogenate, and 50ul of buffer. Put them into the cuvette in that order and do it very quickly. Also, keep the liver and esterase buffer on ice at all times.

Assessment
Oral presentation of results and a laboratory report.


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