Lecture 3 Flashcards
(19 cards)
Explain how each of the following works:
1) g protein-coupled receptor
2) receptor tyrosine kinase
3) receptor guanylyl cyclase
1) GPCR: there must be a receptor present on the cell membrane which binds a ligand. The alpha subunit of the G-protein will bind a GTP (replaces its GDP which is bound to it,) allowing the alpha-GTP to dissociate from the beta and gamma G-protein subunits. The alpha-GTP can now bind/activate another secondary messenger down the road.
2) Receptor tyrosine kinase: a ligand comes in and binds to the receptor, which causes the 2 arms of the tyrosine kinase to swing towards each other and high-five (dimerization) which they autophosphorylate. Phosphorylation will lead to a protein binding to that phosphorylation site through SH2 domains, which will lead to another protein getting pulled in and activated/phosphorylated, then leading to an alteration of gene expression.
3) Receptor guanylyl cyclases: GTP forms cGMP. receptor guanylyl cyclase has its own receptor. Signal comes directly into contact with the guanylyl cyclase which will lead to the production of cGMP from GTP, leading to some response throughout the cell.
Explain how each of the following works:
1) gated ion channels
2) adhesion receptors (integrin)
3) nuclear receptors
1) Gated ion channels: activated through hormones/ligands/action potentials, causing the transmembrane channels to open/close, letting things into the cell based on the concentration and can be pumped through active transport
2) Adhesion receptors: they bind the extracellular matrix and hold the cell where it is (must be released/rebounded for the cell to move)
3) Nuclear receptors: active proteins that enter the nucleus and bind directly to DNA (on/off gene expression). These bind to promoters, enhancer regions, etc. turning on/off gene expression
What’s the difference between neuronal and hormonal signaling?
Neuronal signal is usually neurotransmitters (type of signal that goes between neurons) meaning the signals are between nearby cells.
Hormonal signal is where hormones are carried throughout the body through the blood so that they can go further.
Explain the general scheme of a signaling pathway.
A hormone/signal will bind to a specific receptor, usually leading to a conformational change as soon as it binds the signal/ligand. This change is then signaled in the cell (secondary messenger cascade, adaptor proteins, etc.) Amplification of the signal happens at each of these steps and these secondary messengers will then lead to a bunch of responses, leading to protein activation/inactivation or changes in gene expression.
Give an example of the importance of cell contact signaling.
It’s important for immunity when it comes to the body recognizing itself. Cells will check for surface receptors to see if they are foreign or not. If surface receptors are not present for these signals, then the cells are not recognized by the body and will be destroyed.
Give the general scheme for how nuclear receptors work. Is it fast or slow? What kinds of molecules bind to nuclear receptors?
The hormones are going to pass through the cell membrane and going through the cytoplasm to the nucleus. When in the nucleus, these hormones are going to bind to specific receptors in the nucleus. These receptor-hormone complexes are going to bind to DNA which can then lead to changes in gene expression.
It’s a slow process since we have to recruit all the other proteins necessary to have the protein bind to DNA and expressing/inhibiting the gene.
The kinds of molecules that bind to nuclear receptor are steroid and thyroid hormones, retinoid, and vitamin D. (nonpolar, lipophylic, hydrophobic hormones)
Hormones and neurotransmitters may use the same biochemical mechanisms, but their classification depends on what?
Where these signals came from and where they are going
If it is a nerve releasing something to another nerve across the synaptic cleft, this would be neuronal. If it is the same signaling molecule which is being released into the bloodstream to from a faraway tissue, this would be hormonal.
In order for a hormone to be released by the pancreas, what must occur?
The organ/cell that releases the hormone must be activated/triggered by a signal. Pancreas, for example, needs high blood sugar conditions to release insulin.
List the types of downstream events which follow a hormone binding to a receptor. How specific are these events?
1) A secondary messenger (cAMP, inositol triphosphate, IP3) which is then released inside of a cell to allosterically regulate enzymes. These are allosteric regulators which bind to enzymes and change their conformation, leading to activation or inhibition.
2) Receptor tyrosine kinase becomes activated. Tyrosine kinases are kinases on the cell membrane which take a signal and dimerize. It’s then activated by autophosphorylation, leading to other proteins binding. The result is alteration of gene expression in the nucleus.
3) Hormone gated ion channel become open or closed, resulting in changes to membrane/action potential
4) Adhesion receptors send information to the cytoskeleton. Cytoskeleton holds the shape of the cell, but also moves things throughout the cell. Some of these hormones and certain signals can affect the actin and myosin and things that are holding cells together. Cancer cells take advantage of this process.
5) Lipophilic hormones cross the membrane without any receptors. Then they bind to a receptor within the cell, leading to gene expression.
Explain the 4 classes of action by mammalian hormones.
1) Endocrine: hormones are released into the blood and carried by blood to target cells.
2) Paracrine: hormones are released into extracellular space and diffuse to neighboring targets
3) Autocrine: hormones affect the cell where they are produced
4) Cell contact: signaling molecules fixed to the plasma membrane of one cell interact with the receptors on the membrane of an adjacent cell
What and where are the major endocrine glands?
In the brain, the hypothalamus and the pituitary gland (posterior and anterior).
The thyroid and parathyroid (in your neck).
Fat tissue (adipose tissue all around the body) - very important for the endocrine system because it can store hormones (steroid hormones for example).
Adrenal glands (on top of the kidneys) - this is where you get adrenaline (epinephrine) from.
The pancreas (midsection of body) - releases insulin and glucagon (etc.).
Ovaries/testes - important for estrogen and testosterone production (etc.).
What is the role of the portal vein? What about the lymphatic system?
Portal vein carries nutrients from the intestine to the liver. The lymphatic system carries lipids from the intestine to the liver.
What two hormones are produced by the pancreas? What do these hormones do?
The pancreas produces insulin and glucagon. Insulin lowers blood sugar and glucagon increase blood sugar levels.
Where do water soluble hormones bind to? What occurs after the hormone binds?
Where do lipophilic hormones bind to? What occurs after the hormone binds?
Water soluble hormones bind to external receptors. This leads to an internal secondary messenger, leading to the activation of a pre-existing enzyme, the activation of transcription of that enzyme, etc.
Lipophilic hormone/ligand can cross the cell membrane without a receptor and try to get to the nucleus where the nuclear receptors are. It then binds to the receptor and bind to transcriptional machinery to turn on/off gene expression.
Why is it important that our small intestine is so long? What is the purpose of our small intestine?
Longer small intestine means more surface area which allows for better absorption of nutrients from our diet. It absorbs nutrients from the diet and transports these nutrients into the blood.
Your pancreas has just released insulin into the bloodstream because blood sugar levels were high. In order for metabolic change to occur, what must be present?
The cells must have receptors for the insulin. Because the body is releasing hormones, the cells that need the hormone signal to do something need a receptor for this hormone. If it’s not present, the hormone will ignore it.
What does total binding incorporate? What do they represent?
Total binding = Specific Binding + Nonspecific Binding
Specific binding represents the amount of receptor sites that have a ligand bound at the active site of the receptor.
Nonspecific binding represents binding of the ligand anywhere else but the active site.
Describe the binding sensitivity/affinity of the hormone molecules from left to right on a graph.
If the curve is closer to the left, that means it binds to the receptor at a much lower concentration (this happens really easily, higher affinity.)
As the curve moves to the right, the hormones bind to the receptor at a higher concentration (the binding this doesn’t happen easily, lower affinity)
Three hormones, which all bind to the same receptor, have the following Kd values:
Hormone A: Kd = 5 μM
Hormone B: Kd = 0.4 μM
Hormone C: Kd = 0.0046 μM
Which hormone binds to the receptor with the highest affinity? Why?
Hormone C binds to the receptor better because it requires a much lower concentration such that half of the receptor active sites become filled. This means it really wants to bind to the receptor, meaning it has the greatest binding affinity for the receptor.
