lecture 2 Flashcards
how many types of secreted messengers are there and what are they
5 small water soluble molecules thyroid hormones eicosanoids steroid hormones peptides and polypeptide messengers
what are the 3 types of water soluble secreted messengers
acetylcholine and catecholamines
other messengers from amino acids
how does acetylcholine work as a water soluble secreted messenger
acetylcholine is a neurotransmitter that acts at neuromuscular junctions and at other synapses in the cns and pns
synthesised from acetyl CoA and choline in the nerve terminal
rapidly broken down by acetylcholine esterases
volatile acetylcholine esterase inhibitors were developed as nerve gas for military use as they cause rapid death by paralysis of respiratory muscles
non volatile forms were used as insecticides but these were also toxic
acetyl choline causes muscles to contract and is broken down to allow for relaxation, inhibition of this stops muscles relaxing
how do catecholamines work as a water soluble secreted messenger
act as neurotransmitters and hormones
synthesised from tyrosine
occurs in various nerve terminals and in chromattin cells of the adrenal gland - they secrete adrenaline to the bloodstream
parkinsons diesease is due to the degradation of neurones that are involved in the control of muscle movement and use dopamine as a neurotransmitter
symptoms can be relieved by administration of DOPA
how do other messengers from amino acids work as a water soluble secreted messenger
several are produced by decarboxylation of amino acids to amines
glutamate to y aminobutyrate
histidine to histamine
other amino acids can be used as neurotransmitters in the CNS without modification
how do thyroid hormones work as secreted messengers
thyroxine is made in the thyroid gland from tyrosine residues located within a larger precursor protein called thyroglobulin
2 tyrosine side chains in thyroglobulin are iodinated
2 di-iodotyrosine side chains then combine and proteolytic cleavage releases free thyroxine
T3 the active hormone is mainly produced by de-ionisation of thyroxine in the liver and kidney
eicosanoids as secreted messengers
made from unsaturated fatty acids
prostoglandins and other eicosanoids are made from arachidonic acids by pathways which initial oxidation and cyclisation steps are catalysed by cyclo-oxygenase
other prostoglandins have different substituents on the 5 membered ring or diff numbers of double bonds
cyclo-oxygenase enzymes which catalyse initial oxidation steps are inhibited by non steroidal anti-inflam drugs such as aspirin or ibuprofen
another class of eicosanoid are leukotrienes made by the lipoxygenase pathway
steroid hormones as secreted messengers
based on the sterane nucleus
made from cholesterol by the cleavage of a side chain
the costicosteroid, cortisol, is released from the adrenal gland during stress and starvation
the synthetic analogue, dexamethasone, is used medically to suppress the immune system
male and female sex steroid hormones and synthetic analogues have various uses and abuses - body building and contraception
peptide and polypeptides as secreted messengers
largest group of extracellular messengers
made from amino acids but are encoded in the genome and synthesised on ribosomes
peptide messenger families
peptide messengers are often related
structurally similar peptides often have related functions
oxytocin and vasopressin are small peptides with similar structure both produced on the pituitary
oxytocin causes contraction of smooth muscle of the uterus during child birth
vasopressin increases blood pressure by causing the contraction of smooth muscles that lines blood vessels and water retention in kidneys
oxytocin also binds with low affinity to vasopressin receptors
oxytocin can be used artificially to induce labour but also raises blood pressure due to its affect on vasopressin receptors
insulin, relaxins and insulin like growth factors (IGF)
insulin is released by b cells of the pancreas when blood glucose or amino acids rise promoting the uptake and storage of glucose and amino acids by other cells
relaxin has important effects in pregnant females
IGF1 and 2 are growth factors related in response to somatotrophin
all 4 have regulated regions corresponding to A and B chains of insulin and a conserved pattern of disulphide bridges
A and B of IGFs are part of longer polypeptides
the missing piece in insulin
pancreatic b cells synthesise insulin from the precursor proinsulin
proinsulin has a c peptide, cleaved out by a specific proteinase during transit from the golgiA to the mature storage vesicles in pancreatic beta cells
c peptide has no function other than use in clinic as a biomarker indicating the rate of release of insulin
what are promessengers
precursors to peptide messengers can also be called prohormones
pro-enkephalin family give rise to multiple messengers
peptide messengers effects are mimicked by heroine and morphine
pro-opiomelanocortin and pro-dynorphin give rise to other peptide messengers such as adremocroticotrophin
why are peptides presursors
they are made with targeting sequences that direct them to the secretory pathway and are then cleaved off
some are small, there may be a lower limit as to the size of polypeptide that can be made on ribosomes
making several proteins from 1 gene product by alternative splicing cleavages increases the diversity of messengers that can be produced from a limited number of genes
