Prions are the suspected cause of a wide variety of neurodegenerative diseases in mammals. According to prevailing theory, prions are infectious particles made only of protein and found in high concentrations in the brains of infected animals. All mammals produce normal prion protein, PrP^C, a transmembrane protein whose function remains unclear. 

Infectious prions, PrP^Res, induce conformational changes in the existing PrP^C proteins according to the following reaction:

PrP^C  + PrP^Res  → PrP^Res + PrP^Res

The PrP^Res is then suspected to accumulate in the nervous tissue of infected patients and cause disease. This model of transmission generates replicated proteins, but does so bypassing the standard model of the central dogma of molecular biology. Transcription and translation apparently do not play a role in this replication process.

This theory is a major departure from previously established biological dogma. A scientist decides to test the protein-only theory of prion propagation. He establishes his experiment as follows:

Homogenized brain matter of infected rabbits is injected into the brains of healthy rabbits, as per the following table:

Rabbit 1 and 2: injected with normal saline on days 1 and 2

The above trials serve as controls.

Rabbit 3 and 4: injected with homogenized brain matter on days 1 and 2

The above trials use unmodified brain matter.

Rabbit 5 and 6: injected with irradiated homogenized brain matter on days 1 and 2

The above trials use brain matter that has been irradiated to destroy nucleic acids in the homogenate.

Rabbit 7 and 8: injected with protein-free centrifuged homogenized brain matter on days 1 and 2

The above trials use brain matter that has been centrifuged to generate a protein-free homogenate and a protein-rich homogenate based on molecular weight.

Rabbit 9 and 10: injected with boiled homogenized brain matter on days 1 and 2

The above trials use brain matter that have been boiled to destroy any bacterial contaminants in the homogenate.

Another experiment shows that PrP^C reacts with hormones that circulate among nervous tissue. As a transmembrane protein, what kinds of hormones are most likely to interact with PrPC?

I. Peptide hormones

II. Catecholamines

III. Steroid Hormones

There are two models for the operation of the Golgi apparatus in eukaryotic cells. As it is difficult to visualize the operation of cells at the molecular level in real time, scientists typically rely on static electron micrographs to see the morphology of organelles. As a result, the dynamic operation of these organelles can sometimes be unclear.

Cisternal Maturation Hypothesis

In the cisternal maturation hypothesis, the cisternae of the Golgi apparatus evolve. Proteins leave the endoplasmic reticulum, and enter the cis-Golgi. The cisterna of the cis-Golgi then matures, with its enzymatic contents and internal environment changing as it becomes the medial-Golgi, and, eventually, the trans-Golgi.

In this model, the proteins never physically leave their membrane-bound cisternae during their transit across the Golgi. Instead, the entire unit of contents remains within the evolving cisternae.

Vesicular Transport Hypothesis

In contrast to the cisternal maturation hypothesis, the vesicular transport hypothesis posits that the cis-, medial-, and trans-Golgi cisternae are more static structures. Instead of evolving around their contents, the contents are physically shuttled via vesicular intermediates from each cisterna to the next.

In the case of vesicular transport, vesicles are shuttled along microtubules. Motor proteins facilitate this movement, with unique proteins being used for each direction of movement along a microtubule.

The Golgi is involved in the packaging of many neuronal transmembrane proteins, including membrane ion channels. Which of the following is true of a normal resting membrane potential?

(Note: membrane potential is typically measured relative to the cytosolic face.)

Carbonic anhydrase is a very important enzyme that is utilized by the body. The enzyme catalyzes the following reaction:

A class of drugs that inhibits this enzyme is carbonic anhydrase inhibitors (eg. acetazolamide, brinzolamide, dorzolamide). These drugs are commonly prescribed in patients with glaucoma, hypertension, heart failure, high altitude sickness and for the treatment of basic drugs overdose.   

In patients with hypertension, carbonic anhydrase inhibitors will prevent the reabsorption of sodium chloride  in the proximal tubule of the kidney. When sodium is reabsorbed back into the blood, the molecule creates an electrical force. This electrical force then pulls water along with it into the blood. As more water enters the blood, the blood volume increase. By preventing the reabsorption of sodium, water reabsorption is reduced and the blood pressure decreases. 

When mountain climbing, the atmospheric pressure is lowered as the altitude increases. As a result of less oxygen into the lungs, ventilation increases. From the equation above, hyperventilation will result in more  being expired. Based on Le Chatelier’s principle, the reaction will shift to the left. Since there is more bicarbonate than protons in the body, the blood will become more basic (respiratory alkalosis). To prevent such life threatening result, one would take a carbonic anhydrase inhibitor to prevent the reaction from shifting to the left.  

Carbonic anhydrase inhibitors are useful in patients with a drug overdose that is acidic. The lumen of the collecting tubule is nonpolar. Due to the lumen's characteristic, molecules that are also nonpolar and uncharged are able to cross the membrane and re-enter the circulatory system. Since carbonic anhydrase inhibitors alkalize the urine, acidic molecules stay in a charged state.

How will excess intake of a carbonic anhydratase inhibitor affect the blood's osmolarity if not properly regulated by the body?

Nuclear transport is a very important concept of study in modern cellular biology. Transport of proteins into the nucleus of an organism requires energy in the form of GTP, which is attached to a protein called Ras-related Nuclear protein (RAN).

RAN is a monomeric G protein found in both the cytosol as well as the nucleus and its phosphorylation state plays an important role in the movement of proteins into and out of the nucleus. Specifically, RAN-GTP and RAN-GDP binds to nuclear import and export receptors and carries them into or out of the nucleus. They also play a role in dropping off cargo that import and export receptors hold onto. RAN's functions are controlled by two other proteins: RAN guanine exchange factor (RAN-GEF) and RAN GTPase activating protein (GAP). RAN-GEF binds a GTP onto RAN, while RAN-GAP hydrolyzes GTP into GDP. As a result, there is a RAN-GTP and RAN-GDP concentration gradient that forms between the cytosol and nucleus.

Further research indicates that RAN-GTP and RAN-GDP form a concentration gradient across the nuclear membrane. The nuclear pore is only permeable to RAN-GTP. 

Given that our cells at any given time can only have  total concentration of RAN-GDP, with the cytosol having 3 times the concentration of RAN-GDP than in the nucleus, what can be said about the motion of RAN-GDP across the nuclear membrane? 

Sildenafil (commonly called Viagra) is a common drug used to treat erectile dysfunction and pulmonary arterial hypertension. Sildenafil's effect comes from its ability to cause vasodilation in smooth muscle cells. For this problem, we're only going to consider its effects on erections in males. 

Erectile dysfunction is a common medical problem in older men. Its most significant effect is the prevention of erections. Erections occur when there is an increase in blood flow via enlargement of an artery (vasodilation). Understanding the mechanism by which vasodilations occur is important in order to treat erectile dysfunction.  

Erections occur when nitric oxide  is released from an area in the penis and binds to guanylate cyclase in other cells of the penis, which creates cyclic guanosine monophosphate (cGMP) from GTP. cGMP causes a relaxation of the arterial wall in order to increase blood flow to the region, thereby causing an erection. cGMP is broken down over time by cGMP-specific phosphodiesterase type 5 (PDE5) into GTP, which reverses the effect and causes vasoconstriction on the arterial wall. Combatting this effect is the major method by which Viagra functions. 

cGMP is also found in cells of the eye, and is known to open sodium channels. Given that Sildenafil functions by inhibiting phosphodiesterases, which of the following is also inhibited by Sildenafil in the eye? 

Which of the following organelles is most important in testosterone synthesis?

Type 1 diabetes is a well-understood autoimmune disease. Autoimmune diseases result from an immune system-mediated attack on one’s own body tissues. In normal development, an organ called the thymus introduces immune cells to the body’s normal proteins. This process is called negative selection, as those immune cells that recognize normal proteins are deleted. If cells evade this process, those that recognize normal proteins enter into circulation, where they can attack body tissues. The thymus is also important for activating T-cells that recognize foreign proteins.

As the figure below shows, immune cells typically originate in the bone marrow.  Some immune cells, called T-cells, then go to the thymus for negative selection. Those that survive negative selection, enter into general circulation to fight infection. Other cells, called B-cells, directly enter general circulation from the bone marrow. It is a breakdown in this carefully orchestrated process that leads to autoimmune disease, such as type 1 diabetes.

T-cells use receptors in their activity to defend their biological hosts. These receptors are protein molecules, heavily modified before being sent to the cell's surface. In which organelle does the majority of such modification take place?

A vesicle travelling from the __________ back to the endoplasmic reticulum is most likely contains a __________ protein coat.

Which of the following choices describe functions of the Golgi apparatus?

I. Post-translational modifications

II. Formation of lysosomes

III. Carbohydrate synthesis

IV. Protein trafficking

What is the difference between cytosolic ribosomes and ribosomes on the rough endoplasmic reticulum (RER)?