Take-Home Assignment 2 Key for Fall 2008

Please use the "Talk to Ed and Mike" forum in Moodle if you wish to discuss the assignment further.

The answers here are probably more detailed than we would expect you to have included in your answers, but we want to take another stab at helping you understand these ideas.


Cells and Membranes: (20 points - 10 points per question)

These questions will help you achieve Objectives #3 & 4 for lecture #6.

The diagrams you are asked to produce below are to be your own. DO NOT copy a diagram from the text, the web, or any other source. Your drawings do not need to be beautiful, but they do need to be neat and understandable.


Question 1. Erythropoeitin (EPO) is a human protein that is produced and secreted by specific cells of the kidney. The EPO gene is located on chromosome #7. Erythropoeitin is a hormone that is produced when the oxygen level in the blood passing through the kidney is low. EPO is secreted into the blood stream and flows past all the cells of your body. The hormone interacts with EPO receptor proteins on the surface of red blood cell precursor cells in the bone marrow and stimulates the activation (transcription and translation) of genes that produce proteins that control the maturation of red blood cells. Increasing the number of red blood cells carrying hemoglobin in the blood increases the ability of the blood to carry oxygen from the lungs to all the cells of your body needing oxygen for aerobic respiration. (from MedicineNet.com)

EPO has become the drug of choice for elite cyclists.  Strenuous events like the Tour de France demand tremendous expenditure of energy. Increasing the concentration of red blood cells increases the ability of the blood to deliver oxygen to the muscles to support aerobic respiration, which produces ATP to keep the cyclist going longer and stronger.  Early attempts at "blood doping" were tried by transfusions of red blood cells from a donor or from the cyclist's own blood, collected earlier and held for later use.  Today blood doping is most commonly attempted by administering the protein hormone EPO, produced by recombinant DNA techniques. EPO stimulates the athlete's bone marrow to produce more red blood cells. Tests for blood doping include examination of the blood for abnormal red blood cell content and urine tests that look for the presence of EPO. Doping tests during the 2008 Tour de France placed cyclists under suspicion of using EPO to enhance their performance.
(From The Guardian, July 12, 2008

Describe and/or diagram the production and secretion of the erythropoetin hormone protein by the cells of the kidney.

Explain the involvement of these components of the cells of the kidney in your description and/or diagram:

Hint: This process is very similar to the production and secretion of milk proteins by human mammary gland cells. See text chapter 3 and lecture outline #6.


Ed's Answer:

DNA (the EPO gene) containing the information for the production of the hormone - Erythropoeitin (EPO) (a protein) is stored in the nucleus of all cells of your body. As a reaction to low blood oxygen levels, specific cells of your kidneys initiate the transcription of the information of the EPO gene in their nuclei, to produce mRNA.

The mRNA, carrying the copied code for the EPO hormone then travels out of the nucleus (through the nuclear pore) into the cytoplasm where the mRNA enters a ribocome that becomes attached to the rough endoplasmic reticulum (ER). The mRNA instructs the ribosome to put together the proper sequence of amino acids to produce the initial EPO protein.  Think of this as the beginning of the making of a great cupcake.  This is the baking part.

The new, raw EPO protein enters the membrane spaces of the endoplasmic reticulum as it is manufactured by the ribosome and is further chemically processed by enzymes and packaged into small vesicles by the endoplasmic reticulum.  The processing of the initial EPO protein in the ER is like putting the icing on the cupcake.

The ER vesicles move to and join with the membranes of a Golgi apparatus. In the golgi apparatus the EPO protein is further processed by other enzymes to produce its final form and then packaged in a vesicle formed by the golgi body.  As you know, no self respecting cupcake would be seen without sprinkles - they are applied in the Golgi.

The golgi vesicle moves to and fuses with the cell membrane secreting the completed EPO protein from the cell by exocytosis.  The EPO moves into capillaries of the circulatory system and the hormone is carried to all the cells of your body.

The hormone interacts with receptor proteins on the surface of immature red blood cells in your bone marrow and signals specific genes in the nucleus of those cells to produce proteins (the same process as above).  The new proteins are involved in the maturation process that causes the cells to become mature red blood cells, ready to carry more oxygen from your lungs to your muscles and the rest of your body.  One of the most important proteins produced in the new red blood cells is hemoglobin, the red protein that actually carries oxygen.  Cells not having the EPO receptor proteins on the surface of their cell membranes do not react to EPO. Taking extra artificial EPO enhances the production of red blood cells and gives the "doper" an unfair, increased ability to provide oxygen to his/her muscles.

Drawing Optional

Question 2. Draw a diagram of the cell membrane of one of your bone marrow cells (just a small portion of the outer membrane, not the whole cell)

Illustrate and label these cell membrane components:

As part of your drawing, describe how the jobs of the proteins you were asked to include in your membrane drawing are accomplished. Which protein (or proteins) require(s) the chemical bond energy of ATP to do it's/their job(s)?

See textbook chapter 3 on the structure of the Cell Membrane and Signal Transduction (figure 3.8, pg 56), Chapter 4 on passive and active transport (pg 90-94), and chapter 30, Water-Soluble Hormones Trigger Second Messenger Systems (pg 619-620).

Ed's Answer:

Drawing Required

The backbone of an animal cell membrane consists of two layers of phospholipid molecules with the hydrophobic (water hating) arms of the molecule making up the interior of the membrane and the hydrophilic heads (water loving) making up the two exterior surfaces of the membrane. Transport and receptor proteins are inserted into the membrane. Transport proteins allow for the passage of compounds into and out of the cell, while receptor proteins serve as communication devices for the cell.

Passive transport proteins transport small molecules or ions that do not require energy to enter the cell, but cannot pass through the phospholipid bilayer. Passive transport of water, oxygen, and CO2 across the cell membrane, depends on the concentrations of these materials on either side of the membrane. Movement is from a higher concentration to a lower concentration. Passive movement may be through the phospholipid bilayer for fat-soluble molecules or through protein molecules for others.

Active transport proteins facilitate the movement of large molecules or charged ions across membranes against a concentration gradient - from an area of low concentration to an area of high concentration. This type of transport protein requires energy in the form of ATP. Active transport of larger molecules or charged ions moving against a concentration gradient requires the expenditure of energy in the form of ATP in conjunction with special membrane proteins.

Hormone receptor proteins have specific shapes and chemical properites that allow them to bind to specific types of hormone molecules in the environment of the cell. The example used in this assignment is a receptor protein that bound to a hormone molecule, but there are other types of receptor proteins that interact with lots of other types of molecules and particles. Receptor proteins in the outer cell membrane interact with molecules outside the cell. Receptor proteins in the interior membranes of the cell interact with molecules already in the cell.

In this case, the EPO hormone binds to the EPO receptor protein on the surface of immature red blood cells in your bone marrow and causes them mature and become functioning red blood cells, able to carry oxygen through your blood stream.

Some receptor proteins help the body distinguish between cells of the body and cells invading from outside. Other receptor proteins help the cell parts know how to package molecules and where to send them within the cell. Viruses, like the HIV virus, "know" which of the many different kinds of cells in the body to attack by the receptor proteins located in the outer membrane of the "right" cells.