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Biochemistry Exam 3 > Signals > Flashcards

Signals Flashcards

0
Q

Lipophilic hormones that bind to intracellular receptors

A

Steroids, retinoids, FA derivatives

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1
Q

Two modes of ligand receptor interaction

A

Secreted molecules, membrane to mebrane

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2
Q

Hydrophilic hormones that bind to cell surface receptors

A

Peptide hormones (insulin, growth factors), small charged AA derivatives (histamine, epinephrine)

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3
Q

Paracrine signaling

A

Short range signaling. Ligands have short half life. Developmental signaling molecules like TGF-beta

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4
Q

Endocrine signaling

A

Long range signaling via hormones (such as nuclear hormones). Ligands have long half-life and are synthesized in endocrine organs and travel through blood to reach multiple target organs

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5
Q

Autocrine signaling

A

Cells respond to ligands that the themselves release (feed-back). Growth factors. Embryonic development as well as abnormal growth of tumors.

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6
Q

Gap Junction Signaling

A

Ensure synchronized signaling response. Early development. Muscle, neuron, epithelial cells.

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7
Q

Synaptic signaling

A

The nerve cell releases neurotransmitter into space termed the synapse between the tip of its axon and its target cell

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8
Q

Detail the time and affinity for endocrine signaling

A

Ligand turnover is long half-life long duration. Blood delivery is slow response. Tight binding to receptors give prolonged response.

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9
Q

High affinity receptors lead to what response?

A

Slow and prolonged (endocrine)

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10
Q

Low affinity receptors lead to what response?

A

Rapid response and termination (synapse)

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11
Q

T or F: Signaling is reversible

A

T

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12
Q

T or F: Signaling involves amplification

A

T

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13
Q

T or F: Different signaling pathways can interact

A

T

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14
Q

T or F: One ligand, one receptor, one pathway

A

F, one ligand can activate multiple receptors in multiple signaling pathways

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15
Q

The presence of homologous signaling molecules leads to?

A

Overlapping and distinct function

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16
Q

Describe signaling by phosphorylation

A

Signal in and protein kinase phosphorlaytes protein to “on” signal then sent out. Protein phosphatase to remove P to turn effector off and signal off. ATP signal

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17
Q

Describe nucleotide exchange signaling

A

Signal in and signal dissociates GDP from protein, GTP is added to turn on effector and send signal out. GTP hydrolysis takes GTP to GDP and turns signal off

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18
Q

Source of signal inn phosphate transfer

A

Kinase activity

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19
Q

Source of signal in nucleotide exchange

A

GTP/GDP

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20
Q

Describe how signals are amplified

A

Ligand to receptor to effectors (multiple) to many more downstream effects

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21
Q

Describe signal crosstalk in the context of phosphate and nucleotide signaling

A

G protein secondary messengers activating proteins that interact with other phosphorylated proteins in eliciting cellular response (from MAP kinase for example)

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22
Q

Describe several different effects of acetylcholine

A

Heart muscle decrease rate/force of contraction, skeletal muscle contraction, salivary gland secretion

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23
Q

What are the three major classes of cell surface receptor

A

Ion channel linked receptors, G protein coupled receptors, and enzyme linked receptors

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24
Q

Describe function of ion channel linked receptors

A

Ligand binding changes the conformation of the receptor so that specific ions can flow through it Resulting ion flow causes an electric potential across the membrane

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25
Q

Describe G protein linked receptors

A

Ligand binds a trimeric G protein which in turn activates or inhibits an enzyme that generates a specific second messenger or modulates an ion channel

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26
Q

Describe enzyme linked receptors

A

Receptors with direct enzymatic activity that are activated by ligand binding (e.g. receptor tyrosine kinases, TGF-beta). Receptors that are associated with enzymes. Dimer is formed upon ligation which lead to activation of cystolic protein-tyrosine kinases e.g. cytokine receptor

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27
Q

T or F: The same ligand always activates one specific signaling pathway in different cell types

A

F

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28
Q

T or F: Different signaling pathways can activate the same target molecule

A

T

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29
Q

T or F: Because synaptic signaling must be rapid, it requires high affinity receptors

A

F

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30
Q

T or F: Paracrine signaling is a long distance signaling mechanism in which the signaling molecule travels through the bloodstream

A

F

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31
Q

T or F: Autocrine signaling is a type of endocrine signaling

A

F

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32
Q

What are nuclear receptors (NR) and what are their ligands?

A

Elicit intracellular response by binding to small lipophilic hormones

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33
Q

Ligands for nuclear receptors

A

Small lipophilic hormones

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34
Q

Describe the general pathway of nuclear receptor action

A

Ligands diffuse through the membrane and receptors act as transcription factors in the nucleus

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35
Q

NR signaling is responsible for what general activities in body?

A

Development, cell differentiation, organ physiology, homeostasis (disregulation can lead to cancer, developmental defects, and metabolic disease)

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36
Q

T or F: NR form dimers on DNA

A

T

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37
Q

What are the two types of steroid signaling for NRs?

A

Nuclear intimated steroid signaling (NISS) and Membrane-initiated steroid signaling (MISS) (classical vs rapid).

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38
Q

What is NISS?

A

Nuclear initiated steroid signaling (classical NR steroid signaling)

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39
Q

What is MISS?

A

Membrane initiated steroid signaling (rapid steroid NR sigaling)

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40
Q

NISS signaling generally involves what type of signaling?

A

Gene transcription. Ligand causes conformational change in receptor that complexes with DNA to lead to control of Tx.

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41
Q

T or F: MISS involves multiple signaling pathways

A

T

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42
Q

Describe MISS pathways

A

Steroid hormone receptor associates in outer membrane leading to complex magnitude of membrane protein response leading to phosphphorylation of many different proteins. Rapid response

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43
Q

Describe glucocorticoid receptor activity

A

GR functions to regulate carb, protein, and fat metabolism. Modulates immune anti-inflammatory and immunosuppressive actions. CNS mood and cognitive system responses.

44
Q

What is the HPA axis?

A

Hypothalamo-pituitary-adrenal axis

45
Q

Describe the HPA axis

A

Chronic or acute stress to the brain to the hypothalamus to anterior pituitary to adrenal gland to glucocorticoid to lung,adrenal medulla, immune system, liver, skin, and brain. Feedback to anterior pit, brain, and hypothalamus

46
Q

Glucocorticoids inhibit what immune system effector?

A

Pro-inflammatory cytokines which then promotes brain and hypothalamus on the axis down to glucocorticoid release

47
Q

The hypothalamus releases what to do what in the anterior pituitary on HPA axis?

A

Vasopressin and corticotropin releasing factor to stiulate the release of adrenocroticotropic hormone (ACTH) from anterior pit cells

48
Q

ATCH does what in the HPA axis?

A

Stimmulates the production of glucocorticoids in the adrenal cortex

49
Q

GR have what 5 functions in the HPA axis?

A

Enhance Tx of gluconeogenic enzymes in liver, increase lipolysis in fat, supresses glucose uptake in peripheral tissue, stimulates feeding behavior in CNS, and inhibits over-reactivity to infection (immune suppresion)

50
Q

What is Cushing syndrome?

A

Hypercortisolism (too much glucocorticoid) resulting from adrenal hyperplasia (secondary to the overproduction of ACTH). Manifests as obesity, hypertension, osteoporosis, and diabetes. Primarily caused by pituitary tumor that overproduces ACTH

51
Q

Describe knock-out, knock-in, and conditional knock-out

A

Knock-out removes a gene, knock-in puts in a mutant form of gene, and conditional knock-out knocks out gene in particular tissue

52
Q

T or F: GR knock-out is lethal

A

T (respiration after birth)

53
Q

T or F: Mutation in GR DNA zinc DBD is leathal

A

F, MISS pathway still exists

54
Q

What is the function of mineralcorticoid receptors (MR)?

A

Aldosterone is ligand. Functions in Na+ reabsorption in the kidney by causing reabsorption of salt and water back into the blood.

55
Q

Mutations in MR lead to?

A

Early onset hypertension. In women it can lead to preeclampsia in pregnancy.

56
Q

What type of steroid is cortisol?

A

Glucocorticoid

57
Q

What type of steroid is aldosterone?

A

Mineralcorticoid

58
Q

Testosterone is what type of steroid?

A

Androgen

59
Q

Estradiol is what type of steroid?

A

Estrogen

60
Q

The precursor to all steroid hormones is immediately?

A

Progesterone

61
Q

Function of sex steroid receptors

A

Receptors for estrogens, progesterone, or androgen. Development of sex characteristics and reproductive function

62
Q

Effects of ER knockout in mice?

A

Male mice are infertile! ER has a role in spermatogenesis

63
Q

Describe the link between ER receptors and breast cancer therapy

A

If ER positive, use anti ER therapy. Use aromatase inhibitors to reduce production of estrogen. Use Tamoxifen to be antagonist towards ER cancer cells. Causes potential endometrial malignancy though.

64
Q

What is Androgen insensitivity syndrome?

A

AIS. caused by many different mechanisms that lead to defect in AR. Lead to abnormality in sex organs and characteristics. Range of defect.

65
Q

What is Kennedy’s disease (SBMA)?

A

Adult onset neurodegenerative disease leading to slow, progressive muscle weakness and atrophy. Caused by CAG repeat in the AR gene. Occurs in adult males symptomatically.

66
Q

T or F: AR have a central role in prostate carcinogenesis

A

T

67
Q

Name the three types of non-steroid hormone receptors

A

Thyroid hormone receptor (TR), Vitamin D receptor (VDR), and Retinoic acid receptor (RAR)

68
Q

Type II nonsteroid hormone receptors dimerize with…?

A

RXR (retinoid X receptor)

69
Q

Type I steroid hormone receptors dimerize…?

A

With themselves, homodimers

70
Q

Where do non-steroid hormones receptors constituitively reside?

A

In the nucleus, bound to DNA element. In absence of ligand, they act as Tx receptors. When ligand binds, they activate Tx.

71
Q

T or F: Type II non-steroid hormone receptors require RXR ligand to activate

A

F

72
Q

Non-steroid hormone nuclear receptors use what to activate/deactivate Tx?

A

HAT to activate, HDAC to deactivate (acetylation on histones)

73
Q

Thyroid receptors (TR) function?

A

Control the rate of metabolism

74
Q

What is general resistance to thyroid hormone (GRTH)?

A

Dominant disorder in the ligand binding domain. High circulating levels of thyroid hormones. Hearing defects, mental retardation, learning disabilities, emotional disturbance.

75
Q

Two major types of thyroid hormone

A

T4 (thyroxine) and T3 (triiodothyronine)

76
Q

What is hyperthyroidism?

A

Graves’ disease (overactivity of thyroid gland), excessive intake, hyperproliferation of gland or pituitary tumor, thyroiditis (inflammation of thyroid).

77
Q

What is a thyroid storm?

A

Super high levels of thyroid hormone leading to fever, dehydration, rapid heart rate, heart failure, etc. Use PTU or methimazole to decrease hormone synthesis

78
Q

Vitamin D receptor (VDR) function?

A

Calcium homeostasis, vitamin D metabolism

79
Q

Diseases associated with VDR mutation

A

Rickets, hypocalcaemia, secondary hyperparathyroidism, total absence of hair.

80
Q

What is the function of retinoic acid receptors?

A

Regulation of development and cellular differetiation.

81
Q

What is Acute promyelocytic leukemia (APL)?

A

Mutation in RAR gene involving chromosome translocations

82
Q

T or F: Retinoic acid can be used to treat some forms of (P?)AML?

A

T, if there is only one corepressor, retinoic acid can fix the heterodimer part there. Some have double corepression, not as able to do so

83
Q

Function of orphan receptors?

A

Sense levels of ligands and try to maintain levels (homeostasis)

84
Q

T or F: Orphan receptors heterodimerize with RXR

A

T

85
Q

T or F: Orphan receptors can be activated by RXR ligand

A

T (specific, RXR (9-cis retinoic acid) or both)

86
Q

Simple precursor to cholesterol

A

acetyl CoA

87
Q

Cholesterol has two sources, what are they?

A

Acetyl-CoA and Diet

88
Q

Cholesterol can be made into what two end products?

A

Oxysterol and bile acids

89
Q

Oxysterol inhibits and promotes what?

A

Inhibits SREBP to stop cholesterol formation from Acetyl CoA and promotes LXR (orphan receptor) to take cholesterol to bile acids

90
Q

What is the function of LXR orphan receptor?

A

Ligand is oxysterol to promote cholesterol to bile acids

91
Q

What is function of FXR orphan receptor?

A

Bile acids as ligands and helps with cholesterol removal

92
Q

Function of SREBP

A

Sterol regulatory element binding proteins that are in ER when cholesterol is high, in nucleus when low. Promotes the production of cholesterol in cell

93
Q

Rate limiting enzyme in the production of bile acids

A

Cholesterol 7a-hydroxylase (Cyp7-alpha)

94
Q

Ligand of LXR

A

sterol concentration, upregulates Cyp7-alpha Tx in high sterol levels

95
Q

Function of FXR orphan receptor

A

Senses the level of bile acid and regulates the expression of genes important for bile acid synthesis (from cholesterol) and secretetion

96
Q

What are peroxisome proliferator activated receptors?

A

Lipid sensors with ligands of various FA and FA metabolites. Involved in diabetes, obesity, atherosclerosis and cancer

97
Q

PPARalpha is responsible for?

A

Lipid metabolism. Targets genes that participate in FA uptake through membrane and so on. Can be targeted with fibrates (fate FA) to reduce TAG levels.

98
Q

PPARgamma is responsible for?

A

Glucose and lipid homeostasis. Adipocyte differentation! Ligands are various FA and eicosanoids (like prostaglandin). TZD synthetic compounds can be used here to treat type II diabetes for blood glucose reduction

99
Q

T or F: PPAR alpha knockout is lethal

A

F

100
Q

T or F: PPARgamma knockout is lethal

A

T

101
Q

What is the function of PXR(pregnane X receptor)?

A

Xenobiotic sensor. Targets P450 superfamily. Mediator of drug interactions. Expressed in liver and intestines

102
Q

Orphan receptor activation ususally leads to what effect?

A

Lowering of ligand level by increasing production of enzymes to degrade ligands

103
Q

PXR ligands?

A

Steroid derivatives

104
Q

LXR ligands?

A

Oxysterols

105
Q

FXR ligands?

A

Bile acids

106
Q

PPAR ligands?

A

FA

107
Q

Fibates can be used on what receptors?

A

PPAR alpha

108
Q

TZD can be used on what receptors?

A

PPARgamma

Biochemistry Exam 3 (11 decks)

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