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24 Cards in this Set

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What are the four glycoprotein hormones ('typical'synthesis)and what do they all activate
TSH LS FSH CG
all activate adenyl cyclase
What are the structural features of glycoprotein hormones and what are their activities
alpha chain: same in all glycoprotein hormones, activates adenyl cyclase,

Beta chain: different across hormones, amount of hormone dictated by beta chain

each chain arose from different genes
insulin and angiotensin are two examples of cleavage of peptides to get hormones(prepro->pro->H) describe biochemically the cleavage of insulin
cleave proinsulin at positively charged lys and arg residues


first you do a trypsin like cleavage at the carboxy terminal side of the basic amino acids(lys/arg). Then you cleave off the carboxy at the newly formed end using CARBOXYPEPTIDASE B-like enzyme. Proinsulin is packaged into golgi where removal of c peptide begins in golgi(trans)
Familial cholesterimia and insulin
secrete equal amounts of insulin and proinsulin(usually secreted at about 5%), but apparently normal with respect to glucose metabolism
POMC is an example of what type of hormone?
a polyprotein hormone. Makes ACTH, beta-lipoprotein
POMC gets cleaved in the anterior lobe to what?
ACTH (and side product beta LPH)
POMC gets cleaved to what in the neurointermediate lobe?
POMC -> ACTH -> alpha MSH and CLIP

POMC-> beta LPH ->gamma LPH and beta-END

POMC -> N-term -> gamma MSH and J
Polypeptide hormones can make what type of product?
3 different scenarios
1) products with different aa seq and unrelated activites
2) products with related aa seq and sometimes function
3) multiple repeats of aa seq giving identical copies
Is POMC mono or poly cistronic
Still mono cistronic
a single polypeptide chain will result from mRNA translation, after translation when you have the peptide, THEN you cleave it to ACTH/B-LSH

in contrast to polycistronic mRNA, where translations will yield several polypeptides.
cleavage of POMC: early cleavage is the same in both ant lob and neurointermediate lobe.
but additional cleavage occurs in the intermediate lobe due to the prescence of enzymes not in the adenohypophysis
sdhf
POMC post translational modifications
glycosylation, phosphorylation and alpha amidation

they are common features of neuropeptide hormones and are often essential for activity
what is the characteristic post translational modification of neuropeptide hormones
alpha amidation
ex) ACTH--> alhpa-MSH

mechanism:
1)'typical' cleavage b/w basic aa's(endopeptidase then carboxypeptidase B-like enz)

2) removal of c-terminal basic aa

3)oxidation of C terminal glycine by PAM (peptidyl glycine alpha-amidating monooxygenase) to give an amide(NH2) at the end instead of glycine coo-
why is hyperpigmentation of the skin seen in addisons disease
insufficiency of the adrenal cortex means ACTH isn't inhibited so you have large amounts of it being produced. Since MSH and ACTH come from POMC, msh gets made too??? SEE [age 84
What is the example of a polyprotein cleaved to produce multiple copies of the same protein
opiod-like enckephalins
M1-M6 = Met-enkephalin
L = Leu-enkephalin
Transcriptional control of ACTH and LPH synthesis in the anterior pituitary
Soluble cortisol-receptor complex translocates into the nucleus and exerts a primary effect

POMC mRNA is increased by CRH and adrenalectomy

POMC mRNA is decreased by glucocorticoids
Transcriptional control of alpha -MSH, gamma-MSH, and beta-endorphins in the neurointermediate lobe
mRNA is inhibited by dopaminergic neurons, and stimulated by dopaminergic antagonists
mechanism is unknown
Describe the effects of MSH
MSH binds to Melanocortin-4 receptors on neurons and these neurons suppress appetite.
describe the effects of leptin
leptin is secreted by adipocytes and binds pomc neurons through it's receptor leading to alpha-MSH secretion, MSH suppresses appetite, thus a large amount of fat suppresses appetite

leptin also activates AMP kinase which inhibits acetylCoA carboxylase. Inhibition of acetylcoa carboxylase(makes malonyl CoA) increases FA mobilization
what does Haloperidol do
it is a dopamine antagonist that stimulates POMC-->alpha/gamma-MSH and beta endorphins
what are the consequences of low POMC
low POMC means low MSH which means increased appetite and weight gain with altered lipid metabolism (wt gain out of proportion to food intake)
Explain differential processing of mRNA precursors
its a mechanism for producing different products from a single gene, it's what helps explain some cases of tissue differences
explain the relationship between calcitonin and calcitonin gene-related peptide (CGRP
they are produced from the sa,e gene in different tissues through

Alternative splicing:
Thyroid C-cells = calcitonin
Neurons = CGRP(migraines)
What are the examples of
Post translational
Post transcriptional
processing discussed so far
translational - POMC
transcriptional - CGRP(splice choice)
what is special about thyroxine?
is is cleaved from a large precursoe, but is a modified amino acid

Iodo-Tg -->(cathepsin) T4-gln T3-Gln + aa --> (dipeptidase) T4/T3