Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Glutamate receptor wikipedia , lookup
Biochemical cascade wikipedia , lookup
Lipid signaling wikipedia , lookup
Killer-cell immunoglobulin-like receptor wikipedia , lookup
Paracrine signalling wikipedia , lookup
Purinergic signalling wikipedia , lookup
VLDL receptor wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
Leukotriene B4 receptor 2 wikipedia , lookup
Endocrine (1-27-99) 1st quiz is next week: 20-25 questions 1st hour in the gym 1st assigned chapter + class info You need baseline information on the endocrine system so that you can understand the other things Interdependence of systems (see last week0 Ex – hypothalamic-pituitary-thyroid axis Concepts of: feedback Turn-on/turn-off Other systems use a similar mechanism, just different hormones Innate mechanisms Important for understanding disease Ex – signs and symptoms If the endocrine system operates normally, you don’t see any consequences If it doesn’t, you see consequences (signs and symptoms) Usually due to an abnormality in hormone concentration 1) 2) Why is the hormone concentration increased? How hormones work: Peptide hormones synthesized as parts of larger protein molecules and processed as secretory proteins act via receptors located in the cell membrane with the recognition/binding site exposed on the cell surface and the activity domain facing the inside of the cell receptors provide a sophisticated mechanism of controlling hormone activity ex – if no receptor, the activity of the hormone is negated receptors are proteins that have structural and functional integrity receptors have two essential functional characteristics 1) a recognition site, which binds the hormone with high specificity and affinity 2) an activity site, which transduces the information received into a biochemical message recognition of the hormone is controlled by a number of things: ex – like an enzyme recognizing its substrate depends on the tertiary and quaternary structure if the receptor doesn’t recognize the hormone, there is no interaction activity - ?? nothing said Fig 199-2: shows different receptor structures QQ: What if he gave us this diagram and asked us to fill in the blanks Allosteric receptor proteins: Adopt various conformation Binding of the hormone ligand results in the active configuration If not bound to the hormone, the receptor is in its inactive configuration Getting a hormone to bind to its target cell: Depends on the concentration of the hormone Depends on the concentration of the receptors Depends on the affinity of the receptors Quantitative: depends on the #s of receptors and hormone Qualitative: depends on the effect of affinity/avidity (the tightness of binding) Also – how likely the hormone is to bind to its receptor Ways to increase reaction: Heat the mixture (to increase the # of interactions) Modify the receptor so it binds more tightly/loosely Modify the #s of hormone and receptor QQ: Factors that control the concentration of both the hormone and the receptor determine the biologic responses of cells, of organs, and of the whole organism. Ex – Q – The concentration of the receptor is just as important as the concentration of the hormone. (true/false) TSH and T4 – lag period would get fluctuations if the only method of control was concentration actually, fluctuations are not clinically significant due to receptor responses can alter quality (affinity) faster than you can alter quantity can change receptor #s faster than hormone #s (a lot of Nobel prizes have been given for work done on receptors) some people lack receptors that recognize LDLs their cholesterol levels stay high, no matter what they do so – genes are more important than diet when it comes to cholesterol rate-determining factor for cholesterol control LCAT – hepatic enzyme that degrades cholesterol (happens intracellularly) LDL carries most of the cholesterol Binds to LDL receptors and is brought into the cell Some people lack LDL receptors SOL when it comes to endogenous cholesterol Exercise: enhances cholesterol utilization Tends to qualitatively improve the function of LDL receptors And increase their #s (get more receptors per cell) Innate – protects you from you Receptor protein: recognizes anything that will fit with it If you alter its shape, it can’t interact To alter a reaction: Alter the hormone concentration Alter the relative concentrations of hormone and receptor Receptor regulation: Up regulation Down regulation Some people appear to be euthyroid (‘normal’ thyroid) when they actually have decreased thyroid hormone How? By increasing the #s of their receptors Up regulation: If you decrease hormone concentration, it tends to increase the # of receptors If there are a lot of receptors, it increases the probability of the hormone finding a receptor, and acts as if you had normal levels of the hormone, even though you actually have low levels Down regulation: If you increase hormone concentration, the number of receptors decreases Up/down regulation helps smooth out target cell activity in the face of hormone fluctuations why do the #s of receptors change? Supply and demand receptor sequestation Hormone ligands and receptors bind with high affinities (equilibrium dissociation constants [KD] of nanomolar to picomolar), thus providing the specificity necessary for cells to decode the information provided by the low concentration of hormone present among the many other circulating and extracellular proteins. Also – abnormalities in the receptor Endocrine pathology: 8 basic mechanisms hypofunction: usually decreased concentration or decreased hormone effect hyperfunction: usually increased concentration or increased hormone effect anemia: not a cause but a response/result of something ditto for hyper/hypo ex – hyperthyroid (too much TH) ex – thyroid gland producing too much functional tumor hyperplasia (increased # of cells) ex – trying to compensate for something else hyper: could have elevated ectopic production of the pre-hormone exogenous source of the hormone ex – Cushing’s – can get this if take cortisol over a long period not destroying it fast enough (blocked degradation) enhanced activity on the target cell hypo: destroyed the gland blocked/inhibited the synthesis of the hormone ex – genetic defect metabolic toxins analogs messed up conversion of pre-hormone to hormone enhanced degradation of the hormone decreased action at the target cell antagonists Graves’ – hyperthyroid Antibodies bind to TSH receptors and produce more TSH (act as agonists) Hashimoto’s – hypothyroid Antagonists block TSH from binding Modes of action: Steroid hormones: Synthesized from precursor cholesterol This group acts via structurally related receptors that bind to DNA receptor sites to regulate transcription of target genes. Peptide hormones: Membrane receptors Biologic amplification and 2nd messengers Ex – 1 molecule 25 responses 2nd messenger: once the hormone binds and the message is passed on, you don’t need the hormone anymore activation site turns on the 2nd messenger 2nd messenger does the amplification ex: cAMP: turns on protein kinases via phosphorylation Ca Mg Tyrosine phosphate Diesteryl __??__ Beta blockers: Used for blood pressure and coronary artery dilation Block adrenergic receptors Antagonist calming effect Stimulators: amphetamines, … Steroid: receptors are intracellular (in the cytoplasm or the nucleus) receptors actually transport the message to the cell’s DNA thyroid hormone: needs a receptor carrier proteins: __??__