Graves - PowerPoint PPT Presentation

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Graves

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Graves Disease Case: Previously Normal thyroid signaling requires circuit of signaling: hypothalamus, pituitary, thyroid Signaling between any cells requires ... – PowerPoint PPT presentation

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Title: Graves


1
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 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
2
Whats different in a Graves disease
patient? (hyperthyroidismincreased thyroid
function)
Patients have increased T3 and T4 in bloodstream
What might make a thyroid put in overtime?
YOUR HYPOTHESES?
3
Hypothesis Thyroid being over-stimulated
Normal stimulation results from
TSH/receptor interaction 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?
4
Testing the hypotheses
IF hypothesis is true then what is
expected? What data would suggest the hypothesis
needs to be revised?
5
Protein structure
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
different things?
6
Side chains hold the information
Conventions for writing and speaking about
proteins The N and C termini Polarity of
proteins
7
Can we predict protein structure?
Motifs and Domains
How do you change a proteins shape?
Alter the chain Change the environment what it
is floating in or binding with
8
Levels of Protein Structure
Primary Structure
Secondary Structure
9
Levels of Protein Structure
Tertiary Structure
10
Quaternary structure
Protein Kinase C Interacting Protein.
http//lectures.molgen.mpg.de/ProteinStructure/Lev
els/quaternary.gif
11
TSH Receptor What level of structure?
Extracellular
Plasma membrane
Cytosolic
TSH Receptor from The Thyroid Manager Ch16
12
Graves hypothesis 1 TSH, TSH-Receptorinteractio
n too strong
According to this hypothesis and what we now know
about protein binding
T3 and T4 levels should be _?_ in Graves vs.
normal. TSH levels should be __?__ in Graves vs.
normal TSH/TSH receptor interactions should
show __?___ binding constant vs. normal.
13
Blood tests show
T3 and T4 levels are elevated TSH levels are
decreased TSH/TSH receptor interactions have
same binding constant vs. normal.
Therefore Perfectly logical hypothesis.
14
Now what?
Not supported by data
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