03- Cell Signaling Flashcards
What are the types of hormones and where are they derived from?
- catecholamines and thyroid hormones: derived from amino acids
- steroid hormones and Vitamin D: derived from cholesterol
- prostaglandins: derived from fatty acids
- proteins or polypeptides: derived from translation of hormone specific mRNA
what are some examples of the types of hormones?
catecholamines: dopamine, epinephrine and norepinephrine
thyroid hormones: T3 (triiodothyronine) and T4 (thyroxine)
steroid hormones: cortisol, aldosterone
protein/polypeptide hormones: insulin
what is the function of thyroid hormones?
helps in the metabolism of sugars
how are thyroid hormones synthesized?
- iodide ions are taken into the thyroid follicular cells by the sodium iodide symporter (NIS)
- iodide ions are oxidized to an iodine molecule by the enzyme thyroperoxidase
- iodine is attached to tyrosine residues on a protein which is called thyroglobulin (tyrosine residues are coupled together to form thyronines)
- proteolytic digestion of thyroglobulin then yields T4 and T3 in a 10:1 ratio
what is the half-life of T4 and T3?
the half-life of T4 is 7 days and the half-life of T3 is 1 day
which thyroid hormone is the active form and how is it produced?
T3 is the more active thyroid hormone however, a small concentration is released through proteolytic digestion. Therefore, T3 is produced in the peripheral tissues through the deiodination (removal of a phosphate group) of T4
where are steroid hormones produced?
steroid hormones are produced in the adrenal glands, ovaries, testes and the placenta
how are steroid hormones synthesized?
enzymes in the various glands control the synthesis and final product.
- cytochrome P450c11 which is located in the adrenocortical cells is involved in the production of cortisol. This enzyme is lacking in the gonads because they do not produce cortisol or aldosterone
- gonads produce dihydrotestosterone, estradiol, and progesterone depending on the enzymes present in the gonadal tissue
what is the half-life of cortisol?
60-100 minutes
what are some of the steroid hormones and where are they produced?
progesterone- placenta estradiol- ovary/placenta testosterone- testis cortisol- adrenal cortex corticosterone- adrenal cortex
where does the synthesis of catecholamines take place?
in nervous tissues from which the adrenal medulla is derived
how are catecholamines synthesized?
- phenylalanine is converted to tyrosine by phenylalanine hydroxylase (PA hydroxylase)
- tyrosine is converted to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylases
- DOPA is converted to dopamine and then to nor epinephrine which is released by most catecholamine-producing cells of the body
- in the adrenal medulla and a few other tissues, norepinephrine is converted to epinephrine by methyl transfers
what is the half-life of catecholamines?
1-2 minutes
what is the major source of circulating epinephrine?
adrenal medulla
how are catecholamines synthesized in melanocytes?
- phenylalanine is converted to tyrosine by phenylalanine hydroxylase
- tyrosine is then converted to DOPA by tyrosinase
- DOPA is converted to melanin
what condition is caused by a mutation in tyrosinase/ non-functioning tyrosinase?
albinism
what condition is caused by a mutation in PA hydroxylase/ non-functioning PA hydroxylase?
phenylalanine levels rise and lead to a condition called phenylketonuria
how are prostaglandins synthesized?
- plasma membrane is broken down into Arachidonic acid by phospholipase A2
- arachidonic acid is converted to Prostaglandin G2 or PGG2 by PGH synthase (cyclooxygenase-COX pathway)
- PGG2 is converted to PGH2 by peroxidase
- PGH2 is then converted to a number of prostaglandins including:
- PGI2 (prostacyclin): which is a vasodilator and decreases platelet aggregation
- TXA2 (thromboxane): which is a vasoconstrictor, and bronchoconstrictor and increases platelet aggregation
- PGF2a: uterine contraction and pregnancy regulation
- PGE2: fever and pain
what are the 2 catalytic activities of PGH synthase?
- cyclooxygenase pathway (COX)
- peroxidase
what is phospholipase A2 inhibited by?
steroids
what is the cyclooxygenase pathway (COX) inhibited by?
aspirin, indomethacin and other NSAIDs
how are leukotrienes synthesized?
- plasma membrane is broken down into Arachidonic acid by phospholipase A2
- arachidonic acid is converted to several leukotrienes by the lipoxygenase pathway (LOX) including:
B4: chemotaxis which affects immune cells
C4, D4, E4: bronchoconstriction
what are leukotrienes synthesized by?
montelukast
what is the half-life of prostaglandins and leukotrienes?
a few seconds
How is amplification done in a signaling pathway?
Each protein in the signaling pathway amplifies the signal by activating multiple copies of the next component in the pathway.
1 primary signal activates an enzyme activity that processes 100 substrates per second. The primary enzyme activates 100 target enzymes, and each of the 100 target enzymes activates an additional 100 downstream target enzymes. Each of the 10,000 downstream targets activates 100 control factors so rapidly have 1,000,000 active control factors.
what is signaling?
cell-cell communication via signals
what is signal transduction?
process of converting extracellular signals into intra-cellular responses
what is a ligand?
the signaling molecule
what is a receptor?
it binds specific ligands and transmits signals to intracellular targets
what are the components involved in signaling?
ligands, receptors, intracellular signaling proteins: intermediary proteins, enzymes, second messengers, target proteins and inactivating proteins
what are the types of signaling?
1) contact-dependant: via proteins in the plasma membrane
2) via secreted signals:
- autocrine: via growth factors, the cell releases the signal that is also the target
- paracrine: via neurotransmitters and cytokines, action on adjacent target cells
- endocrine: via hormones, action on distant target cells
- synaptic: via neurotransmitters, action on post-synaptic cell in response to electrical stimuli
what are the types of signaling ligands?
A) Ligands that bind to cell-surface receptors:
- neurotransmitters, e.g. norepinephrine, histamine- hydrophilic
- peptide hormones e.g. insulin- cannot cross membrane
- growth factors e.g NGF, EGF, PDGF
- lipophilic signaling molecules e.g. prostaglandins
B) Ligands that bind to intracellular receptors
-lipid soluble hormones that diffuse across the plasma membrane and interact with receptors in the cytosol or nucleus e.g. steroids, thyroxine, retinoic acid, nitric oxide