Graves’ Disease Case: Previously. Normal thyroid signaling requires circuit of signaling: hypothalamus, pituitary, thyroid. Signaling between any cells requires signals and receptors 5 types of extracellular signaling What they are and how they work
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Normal thyroid signaling requires circuit of signaling:
hypothalamus, pituitary, thyroid
Signaling between any cells requires signals and receptors
5 types of extracellular signaling
What they are and how they work
4 classes of receptors (only showed list)
Receptors: What are they (describing all of them)
Now: More details on the 4 classes of receptors
Hypothesizing what goes wrong in Graves’
(hyperthyroidism=increased thyroid function)
Patients have increased T3 and T4 in bloodstream
What might make a thyroid put in overtime?
Normal stimulation results from TSH/receptor
How does the thyroid know to react?
How does a receptor provide specificity
Hypothesis: Mutation in signaling within cell leading
increase in thyroid hormone production
Normal activation is the result of signal transduction
second messenger cascade
How does signal transduction work?
What could have gone wrong?
Known: Normal stimulation results from TSH/receptor
How does the thyroid ‘know’ to react?
How does a receptor provide specificity?Testing the hypotheses
IF hypothesis is true then what is expected?
What data would suggest the hypothesis
needs to be revised?
Amino acid sequence and folding environment
determine the conformation of a protein
Parts of a protein: amino acids
Amino acids: 5 characteristic parts
If all proteins made of amino acids and all amino
acids have the same parts why do proteins do
Conventions for writing and speaking about proteins:
The N and C termini
Polarity of proteins
Motifs and Domains
How do you change a protein’s shape?
Alter the chain
Change the environment–
what it is floating in or binding with
Protein Kinase C Interacting Protein.http://lectures.molgen.mpg.de/ProteinStructure/Levels/quaternary.gif
TSH Receptor:from “The Thyroid Manager” Ch16
According to this hypothesis and what we
now know about protein binding……
T3 and T4 levels should be _?_ in Graves’
TSH levels should be __?__ in Graves’ vs.
TSH/TSH receptor interactions should show
__?___ binding constant vs. normal.
T3 and T4 levels are elevated
TSH levels are decreased
TSH/TSH receptor interactions have same
binding constant vs. normal.
Therefore: Perfectly logical hypothesis…….