Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BIOL 432 > Peptide Hormone Mechanisms & Biosynthesis > Flashcards

Peptide Hormone Mechanisms & Biosynthesis Flashcards

1
Q

peptide/protein hormones are the….

A

most numerous type of hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

many peptide hormones belong to____

A

families that share genetic and peptide structure homologies - essential for aspect of conformation and biological activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

where are many of the peptide hormones produced from?

A

hypothalamus, anterior pituitary, pancreas, nontraditional endocrines cells (ie GI tract)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

where does hormone synthesis of peptide hormones take place?

A

the nucleus and cytoplasm of secretory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

peptide hormone gene transcription

A

form precursors RNA molecule from DNA in the nucleus -> mediated by RNA polymerase II

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what happens with peptide hormone precursor RNA transcript?

A

post transcriptional modifications in the nucleus -> excision of intron sequences

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

peptide hormone translation…

A

of mature mRNA into the encoded peptide chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what happens to the peptide chains?

A

cotranslational and posttranslational modifcations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what does the start of the mRNA encode?

A

a signal sequence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what does the signal sequence do?

A

indicate that peptide hormone must be packaged for secretion, therefore it must be translated in the ER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is produced first: active hormone, prohormone, prehormone, preprohormone

A

preprohormone first - has the signal peptide causing the protein to be translated in the ER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what happens after the signal peptide causes translation?

A

the signal sequence is then cleaved enzymatically to produce prohormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

describe the prohormone

A

not biologically active, may need to be processed/cleaved to produce biologically active hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

most peptide hormones only require ________

A

transcription of a single gene -> ie human INS gene (insulin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what are the exceptions? (where transcription of 2 genes is required)

A
  • Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Thyroid-stimulating hormone (TSH) and human chorionic gonadotropin (hCG)
  • Heterodimers with alpha and beta subunits (encoded by two different genes) and carb side chains
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

describe heterodimers

A

have alpha and beta subunits encoded by two different genes on separate chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

alpha subunit

A

encoded by same gene for all four hormones (FSH, LH, TSH, hCG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

beta subunit

A

unique for each hormone, gives biological specificity
-> designates the specific hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how are the subunits linked?

A

covalently

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

can also have ____ encode multiple hormones, or a hormone requiring _____

A

one gene, two different genes
-> E.g. same cell produces LH and FSH, which one is currently produced is determined by increased expression of LH gene vs. FSH gene.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

genes

A

Consist of coding regions (exons + introns) and regulatory regions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

coding regions

A

– exons containing nucleotide sequences that are conserved in mature mRNA + intron (intervening) sequences excised during posttranscriptional modification of RNA transcript in nucleus
- encode protein in question

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

promoter region

A

most important regulatory region, 5’ end of gene immediately upstream of first transcribed nucleotide; needed for accurate initiation and efficiency of transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

whats included in the promoter region?

A

initiator element, regulatory elements, enhances/silencers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

initiator element

A
  • has transcription start site 25-30 nt downstream of TATA box
  • required for correct initiation of transcription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

regulatory elements

A

specific binding sites for various transcription factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

transcription factors

A

proteins that initiate, activate, or repress transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

enhancers/silencers

A

regulatory regions - binding sites for activators or repressors, are usually further upstream or downstream of promoter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

peptide hormone gene expression

A
  • DNA: tightly packaged (e.g., histone proteins forming nucleosomes, which bundle together)
  • To allow dynamic access to condensed DNA, chromatin remodeling alters this architecture
    to expose or hide regions for transcriptional regulation.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what could gene expression of peptide hormones involve

A
  • histone modifying enzymes (eg HATS, add acetyl group to histones, causing more open conformation - vs histone deacetylates, HDACs)
  • ATP dependent chromatin remodeling complexes can move, eject or restructure nucleosomes to expose binding sites for transcription activators or repressors at gene promoters or enhancers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

in the promoter region, the pre initiation complex forms….

A
  • incl RNA polymerase II (enzyme that transcribes genes to mRNA), general TFs and other regulators (specific TFs, chromatin, remodeling complexes, etc)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

once transcription is initated….

A

RNa polymerase II continues to elongation until a sequence is transcribed that signals cleavage and polyadenylation of RNA : transcription termination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

pre-mRNA/mRNa processing

A
  • (during transcription): 5’ end of RNA is capped with modified guanine nucleotide (7-methylguanosine)
  • Key for nuclear export, translation and stability
  • 3’ end is polyadenylated (adenosine residues added)
  • Key for nuclear export, translation and stability
  • Introns (intervening sequences), spliced out, and exons (expressed) plus 5’ and 3’ UTRs (untranslated regions) ligated
  • Mature mRNA is exported via nuclear pore
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

calcitonin

A

32-a.a. peptide hormone secreted by the thyroid gland. Reduces blood calcium, opposing the effects of parathyroid hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

calcitonin gene related peptide

A

37-a.a. peptide primarily secreted in nervous system. Vasodilator, implicated in sensing pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

alternative splicing enables _____ of a hormone receptor

A

synthesizing variants
- eg there are two splice variants of the insulin receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

T/F: protein and mRNA are degraded at variable rates (often fast for signaling molecules like hormones)

A

true, 5’ mRNa cap and length of 3’ poly a tail affect mRNa half life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

regulation at the level of a hormones receptor is also an important…

A

point of endocrine function control
- eg increasing or decreasing receptor synthesis in target cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

hormone receptors (as well as specific blood binding proteins) are comprised of proteins…

A

therefore encoded by genes
- subject to the same types of regulatory control of their genes transcription/translation as peptide hormones
- some hormones affect the synthesis of their own receptors ( feed back regulation)
– hormones might regulate their target genes at transcriptional, post- transcriptional, and/or post-translational levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

stages of peptide hormone translation (mRNa to protein)

A
  • initiation stage
  • elongation stage
    -termination stage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

mature mRNA

A

template for assembling amino acids via tRNAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

translation of mRNA to protein starts at…

A

specific site on mRNa = start codon (usually AUG, encodes methionine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

translation will continue until…

A

a stop codon is reached

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

initiation stage

A

ribosome (small subunit first) and initiation factors assemble at 5’ mRNA cap, and scan for start codon; the first tRNA [with methionine] is attached at the start codon

45
Q

elongation stage

A

peptide bond between methionine and subsequent amino acid, and assembled ribosome translocates three nucleotide along the mRNA

46
Q

termination stage

A

when stop codon is reached, ribosomal subunits dissociate and releases the polypeptide and mRNA

47
Q

translation =

A

energetically costly, driven by ATP/GTP hydrolysis

48
Q

initiation usually involves…

A

interactions of certain key proteins ( the initiation factors) with 5’ mRNA cap. these proteins bind the small (40S) ribosomal subunit and hold the mRNA in place

49
Q

peptide hormones are stored and secreted from

A

secretory vesicles - therefore, must be synthesized within the rough ER

50
Q

first amino acids that are translated from the ___ template form a _____

A

mRNA, signal sequence
-> causes the nascent peptide chain to enter a secretory pathway. the signal sequence bind to a signal-recognition particle (SRP), which docks with an SRP receptor complex

51
Q

a translocation channel…

A

transports the nascent peptide chain into the ER lumen; translation continues

52
Q

most peptide hormones are synthesized…

A

as large precursors, which then undergo several modifications during and/or after translation
-> eg preprohormone (w/ signal sequence) -> prohormone -> mature hormone

53
Q

after the transfer of ___ to the ER membrane…

A

ribosomes, the growing polypeptide chain enters the ER lumen as translation continues, and the signal sequence is rapidly cleaved enzymatically

54
Q

additional modifications that may occur during translation in ER lumen (contributing to the stability and folding of the final peptide hormone product)

A
  • covalent addition of oligosaccharide side chains (glycosylation)
  • folding and assembly of proteins, and quality control (mediated by molecular chaperones in the ER)
  • disulphide bond formation
55
Q

once translation is terminated and proper folding and assembly have occurred…

A

the hormone or prohormone is transferred to golfi apparatus (membranous regions)

56
Q

in the golgi further processing may incl…

A

proteolytic cleavage, glycosylation/modifications of carbohydrates, acylation, acetylation, phosphorylation

57
Q

incorporated into _____, often as ______: cleavage by a prohormone convertase (PC) needed to produce ______

A

secretory granules (membrane vesicles), inactive prohormone, active hormone

58
Q

proglucagon is processed in a

A

tissue specific manner, depending in part on the local dominant prohormone convertase (PC)

59
Q

in pancreate alpha cells, glucagon is

A

synthesized (‘opposes insulin: raises blood glucose)

60
Q

enteroendocrine cells synthesize

A

glucagon-like peptides (GLP)
-> GLP-1: a peptide hormone which amplifies glucose-stimulated insulin secretion (among other effects)

61
Q

post-translational modifications in the ER and golgi apparatus:

A

can regulate bioactivity and or synthesis of different hormones

62
Q

insulin post translational processing

A

preproinsulin -> proinsulin -> c-peptide + insulin

63
Q

preproinsulin

A

110-a.a., biologically inactive. In ER.

64
Q

proinsulin

A

86-a.a., biologically inactive.
- In ER:folding, disulphide bonds
- In Golgi apparatus:further modifications (glycosylation)

65
Q

c-peptide

A

31 aa, cleaved in secretory granules

66
Q

insulin

A

51 aa
- biologically active as monomer. in secretory granules

67
Q

peptide hormones are released from secretory granules…

A

by exocytosis
- cytoskeletal protein-mediated migration of vesicles toward cell surface, vesicle (granule) fusion with the plasma membrane, expulsion of contents (eg hormones) into extracellular space

68
Q

what happens during sorting of exocytosis

A

Specific proteins meant to be secreted are concentrated into secretory granules at the far side of the Golgi apparatus. Sorting receptors that “gather” specific vesicle cargo help mediate this.

69
Q

what happens during budding of exocytosis

A

Proteins that coat membrane-bound transport vesicles gather and cause vesicle to break free. These coat proteins mediate transfer of vesicles within the cell.

70
Q

what happens during trafficking

A

vesicles moved via motor proteins along cytoskeleton (e.g. microtubules); requires energy.

71
Q

what does trafficking require

A

energy (ATP, also myosin required)

72
Q

what happens during docking/fusion

A

mediated by interactions with docking proteins at the destination site

73
Q

exocytosis is

A

regulated
-> is not continuous but rather acutely triggered in response to a stimulus

74
Q

what is exocytosis triggered by

A

changes in calcium concentrations in the cytoplasm that affects secretory granule fusion

75
Q

exocytosis results in ____ secretion…

A

acute, allowing for a rapid release of a large amount of hormones

76
Q

what factors may stimulate exocytosis

A

metabolites, other hormones, or neuropeptides or direct nerve innervations

77
Q

secretory granule release is

A

an important control point for peptide hormones

78
Q

secretion of peptide hormones is

A

pulsatile, may be rhythmic

79
Q

why is pulsatile release important

A

crucial for physiological function due to the fluctuating levels of hormones during secretion

80
Q

how does the freq of pulses vary among diff peptide hormones

A

some exhibiting intervals of 4-30 minutes, while others may have longer intervals of 45-180 minutes

81
Q

what about amplitude of pulsatile release?

A

it varies, for anterior pituitary hormones, it may undergo 1000-fold changes during secretion

82
Q

what patterns may hormones exhibit in terms of rhythmic changes

A

rhythmic changes, such as bursts every hour, every ~24 hours (circadian), or even longer intervals

83
Q

what factors could influence the rhythmic changes in hormone secretion?

A

by environmental stimuli, such as the light-dark cycle, or an internal biological clock

84
Q

example of hormone with notable circadian rhythm

A

Adrenocorticotropic hormone (ACTH), which exhibits a circadian rhythm characterized by high levels during the early morning hours

85
Q

what hormones, associated w the menstrual cycle have peaks approx every 30 days

A

Gonadotropins, specifically Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH), have peaks every ~30 days during the menstrual cycle.

86
Q

characteristics of peptide hormones in terms of solubility

A

most are soluble in aqueous solutions, making them hydrophilic

87
Q

how do peptide hormones travel in blood stream

A

do not require blood binding proteins bcuz are soluble in aq solutions

88
Q

what is consequence from solubility of peptide hormones

A

makes them vulnerable to rapid degradation, resulting in short plasma half life and duration of action

89
Q

how do blood binding proteins influence the release and stability of hormones?

A

affect the controlled release and stability of the hormone pool, providing a reservoir and influencing solubility

90
Q

what increases in hormone solubility important

A

blood binding proteins, benefit hydrophobic hormones like steroid hormones

91
Q

what does growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis regulate

A

linear growth in children and adolescents

92
Q

what is the structure of GH and where is it synthesized

A

191 aa polypeptide synthesized by anterior pituitary

-> approx half in circulation is bound to specific GH-binding proteins, reducing oscillations and prolonging half-life

93
Q

what is the structure of IGF-1 and where is it synthsized

A

70 aa polypeptide, synthesized by many tissues, acting in a paracrine/autocrine manner

-> most circulating is produced by liver and its bioavailabity is determined by specific IGF binding proteins

94
Q

protein/peptide hormones are often ____ after being _____ by target cells

A

degraded, internalized

-> eg receptor mediated clearance: hormone degraded in intracellular lysosomes)

95
Q

how else can peptide hormones be degraded

A

by non target cells, or cleared/filtered by kidney
- also by extracellular proteases

96
Q

many peptide hormones circulate in

A

free form (exceptions: GH, IGF-1), therefore rapid degradation/short duration of action

97
Q

type 2 diabetes

A

Initially, failure of target cells to adequately respond to insulin; in later stages, insulin biosynthesis in β-cells is impaired

98
Q

GLP-1

A

a peptide hormone which amplifies glucose- stimulated insulin secretion, among other effects

99
Q

control points for hormone levels

A

important for healthy physiological function (changes in hormone levels due to environmental & internal changes mean that hormones to carry out their intended function of communicating/ causing appropriate responses within the body)

100
Q

what happens when a hormone interacts w its specific receptor on a target cell

A

triggers cascade of biochemical rxns in the target cell, eventually modifying the cells function or activity

101
Q

what are the main types of cell surface receptors for peptide hormones

A
  • G-protein-coupled receptors
    (or “7-transmembrane receptors”)
  • Receptor tyrosine kinases
    (or “growth factor receptors;” have tyrosine kinase domain)
  • Cytokine receptors
    (assoc. with an accessory protein with a tyrosine kinase domain)
  • Guanylyl cyclase receptors (have guanylyl cyclase domain)
102
Q

interactions btwn hormones and their receptors depend on…

A
  • number of receptors
  • affinity of the hormone
  • concentration of circulating hormone
103
Q

regulation at the level of the receptor is also important point of endocrine function control…

A
  • increasing or decreasing receptor synthesis
  • internalization vs cell membrane localization of cell surface receptors
  • desenitization of receptors (‘uncouple’ from signal transduction pathway due to such mechs as phosphorylation of receptor)
104
Q

define these: [H], [R], [HR], k+1, k-1

A

[H] = concentration of free hormone
[R] = concentration of free receptor
[HR] = concentration of hormone-receptor complex
(hormone bound to receptor)
k+1 = rate constant for [HR] formation
k-1 = rate constant for [H] + [R] formation

105
Q

cells with more receptors will have…

A

a greater response (more [HR]) at a given concentration of hormone

106
Q

higher concentration of hormone will lead to more

A

[HR]

107
Q

what is kd

A

equilibrium dissociation constant that defines the affinity of the hormone receptor binding

  • lower kd the higher affinity of receptor for the hormone
108
Q

what is ICYP

A

Iodocyanopindolol (ICYP) is a β-adrenoceptor antagonist. Its [125I]-radiolabeled derivative has been used to map the distribution of β-adrenoceptors in the body.

BIOL 432 (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions