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24 Cards in this Set
- Front
- Back
What are the four glycoprotein hormones ('typical'synthesis)and what do they all activate
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TSH LS FSH CG
all activate adenyl cyclase |
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What are the structural features of glycoprotein hormones and what are their activities
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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 |
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insulin and angiotensin are two examples of cleavage of peptides to get hormones(prepro->pro->H) describe biochemically the cleavage of insulin
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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) |
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Familial cholesterimia and insulin
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secrete equal amounts of insulin and proinsulin(usually secreted at about 5%), but apparently normal with respect to glucose metabolism
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POMC is an example of what type of hormone?
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a polyprotein hormone. Makes ACTH, beta-lipoprotein
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POMC gets cleaved in the anterior lobe to what?
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ACTH (and side product beta LPH)
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POMC gets cleaved to what in the neurointermediate lobe?
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POMC -> ACTH -> alpha MSH and CLIP
POMC-> beta LPH ->gamma LPH and beta-END POMC -> N-term -> gamma MSH and J |
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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 |
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Is POMC mono or poly cistronic
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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. |
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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
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POMC post translational modifications
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glycosylation, phosphorylation and alpha amidation
they are common features of neuropeptide hormones and are often essential for activity |
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what is the characteristic post translational modification of neuropeptide hormones
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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- |
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why is hyperpigmentation of the skin seen in addisons disease
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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
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What is the example of a polyprotein cleaved to produce multiple copies of the same protein
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opiod-like enckephalins
M1-M6 = Met-enkephalin L = Leu-enkephalin |
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Transcriptional control of ACTH and LPH synthesis in the anterior pituitary
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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 |
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Transcriptional control of alpha -MSH, gamma-MSH, and beta-endorphins in the neurointermediate lobe
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mRNA is inhibited by dopaminergic neurons, and stimulated by dopaminergic antagonists
mechanism is unknown |
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Describe the effects of MSH
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MSH binds to Melanocortin-4 receptors on neurons and these neurons suppress appetite.
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describe the effects of leptin
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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 |
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what does Haloperidol do
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it is a dopamine antagonist that stimulates POMC-->alpha/gamma-MSH and beta endorphins
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what are the consequences of low POMC
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low POMC means low MSH which means increased appetite and weight gain with altered lipid metabolism (wt gain out of proportion to food intake)
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Explain differential processing of mRNA precursors
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its a mechanism for producing different products from a single gene, it's what helps explain some cases of tissue differences
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explain the relationship between calcitonin and calcitonin gene-related peptide (CGRP
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they are produced from the sa,e gene in different tissues through
Alternative splicing: Thyroid C-cells = calcitonin Neurons = CGRP(migraines) |
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What are the examples of
Post translational Post transcriptional processing discussed so far |
translational - POMC
transcriptional - CGRP(splice choice) |
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what is special about thyroxine?
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is is cleaved from a large precursoe, but is a modified amino acid
Iodo-Tg -->(cathepsin) T4-gln T3-Gln + aa --> (dipeptidase) T4/T3 |