Endocrine and Exocrine & Intro to Cell Signaling Flashcards
Diagram of exocrine and endocrine gland
What is the difference between endocrine and exocrine glands?
- Endocrine glands are distinguished from another type of gland in the body called exocrine glands.
- Exocrine glands secrete their products into a duct, from where the secretions either exit the body (as in sweat) or enter the lumen of another organ, such as the intestines.
- By contrast, endocrine glands are ductless and release hormones into the blood.
Where are hormones usually released?
Hormones are actually released first into interstitial fluid, from where they diffuse into the blood, but for simplicity, we will often omit the interstitial fluid step in our discussion.
Transport of glucose through the epithelium
- Sodium and glucose are coupled in the same transporter (secondary active transport through a symporter)
- Sodium has a high concentration in the lumen and low in the cell, so there is a strong diffusion gradient
- Glucose has a low concentration outside and high concentration inside
How are glucose and sodium transported from the cell into the intracellular fluid -> rest of the body (after being transported into the cell from the lumen)?
- There is a high concentration of glucose in the cell and lower outside so facilitated diffusion is used
- Sodium needs to be pumped out using active transport (primary) and this is coupled with the movement of potassium in using an antiporter (sodium-potassium pump)
What is Cystic Fibrosis an example of?
Example of:
protein structure/function;
membrane transport;
osmosis and;
exocrine function
Symptoms of Cystic Fibrosis
- Thick secretions in lungs and digestive tract (exocrine)
- Excessive salt in sweat
- Thick secretions in the lungs and GI tract cause difficulty breathing (lungs) and insufficient secretions of digestive enzymes (leading to malabsorption of nutrients –> malnutrition)
Incidence of CF in different ethnicities
- 1/3000 white live births
- 1/17,000 black live births
- 1:377 white live births (England)
- 1:90,000 live births (Asia)
Strong genetic implications…
Causes of CF
- 70% of CF cases are caused by a mutation in chromosome 7
- Deletion of a single amino acid (phenylalanine)
- This is amino acid 508 of 1480 – the CF Transmembrane Regulator protein
- CFTR is a Chloride transporter found in epithelial cells within the airways, pancreas, GI system, and sweat glands (EXOCRINE GLANDS)
What is CFTR?
- A chloride transporter found in epithelial cells within the airways, pancreas, GI system, sweat glands (exocrine)
How does the CFTR mutation affect the lungs and GI tract?
- Digestive enzymes have to be secreted into the lumen of the GI tract
- In order to get those enzymes out, we also have to secrete sodium, chloride, and water, which forms the bulk of the solution that’s secreted to carry the enzymes into the lumen
- If you don’t secrete enough sodium, chloride, and water in the right proportion, it’s not going to have enough volume
- Also, the cells lining the duct that secretes the enzymes have to protect themselves by secreting mucus
- If the ratio of the secretion of mucus and saltwater is not correct, the consistency of the secretion will be off - if there’s not enough sodium chloride and water, it’s going to be too thick/too mucusy and the enzymes aren’t going to get out into the lumen effectively
- The transport of sodium, chloride, and water are all linked to each other. Since the mutation of the CFTR gene causes chloride not to be secreted, there is no anion (negative ion) to join sodium so, it cannot be secreted, and water is not going to follow.
- Instead, there will be excessively thick, mucusy secretions. This makes it difficult to get air through the airways & get particles out of the airways if they get stuck
How does the CFTR mutation affect the sweat glands?
- The cells that form the sweat are at the bottom of the sweat gland. Sodium, chloride, and water are ok there (?)
- As the sweat travels up the sweat gland, it is beneficial to reclaim sodium and chloride and not let it get lost out into the surface of the skin (you don’t need sodium and chloride in sweat to cool down; you need water)
- There are transporters for sodium and chloride that reclaim the sodium and chloride as the sweat goes up the duct. If you interfere with the chloride transport, it prevents sodium from being reclaimed, and so more sodium and chloride is in the sweat.
Construction of CFTR protein (and where it can go wrong)
TMD = trans-membrane domain NBD = nucleotide-binding domain (binds ATP to transport Cl-)
How does the CFTR mutation change the chloride channel?
- The mutation doesn’t interfere with the function of the channel, but rather changes the 3-dimensional shape of the protein such that it doesn’t get transported in the right location in the membrane
- It’s recognized on the intracellular police that recognize misshapen proteins and it’s prevented from being inserted into the membrane. It gets destroyed by cellular processes that destroy proteins
- The protein is perfectly functional, but it gets destroyed (because it’s misshapen) before they can be inserted into the membrane
Latest treatments to address the primary cause of CF
- Drugs that chaperone CTFRΔF508 to the cell membrane
- Drugs that increase the conductance of Cl through CTFR transporters
In current clinical trials - Extremely expensive ($300,000 per person/year)
Gramicidins: Mechanism of action
- The gramicidins behave as ionophoric substances
- The gramicidins self-associate (dimers) forming small pores that cause leakage of cations from the cytoplasm
Intro to cell communications
a. Gap Junctions
b. Surface Protein interaction
c. Chemical Messengers
Chemical communication- nervous system
- Fast (response in msecs)
- Discrete message to specific cells
Chemical communication- endocrine system
- lower (response in secs- mins- years)
- Broadcast message to many cells
