Signal Transduction and Basic Concepts and Design of Metabolism
Signal-transduction
the conversion of information into a chemical change
biosignaling
the signal represents information that is detected by specific receptors and converted to a cellular responses
always involves a chemical process
principles
release of the primary messenger
reception of the primary messenger
relay of information by the second messenger
activation of effectfors that directly alter the physiological response
termination of the signal
benefit of using secondary messenger
free to diffuse to other compartments of the cell
the signal may be amplified significantly by generation of secondary messenger
receptor proteins
seven-transmembrane-helix receptors
dimeric receptors that recruit protein kinases
dimeric receptors that are protein kinases
change conformation in response to ligand binding and activate G protein
~50 % drugs that we use alter receptors of this class
protein : G protein-coupled receptors (GPCRs)
generates an intracellular second messanger and a guanosine nucleoide-binding protein (G-protein)
beta-adrenergic receptor, a prototype of all GPCRs
the fight or flight response occurs when a person is subject to a treat
causes a signaling process to occur for the body to react to the potential danger
once a threat is perceived, a signal is sent to the brain. the brain then sends nerve impulses to the adrenal gland in the kidneys to release epinephrine
how is the signaling pathway switched off?
the phosphoinositide cascade
a receptor that dimerizes on ligand binding and recruits tyrosine kinases to propagate the signal
some receptors contain tyrosine kinase domains within their covalent structure
growth factors and hormones bind to extracellular domains of transmembrane receptors that have tyrosine kinase domains within their intracellular domains
mutation in these receptors cause a range of pathologies including cancer, inflammation and type 2 diabetes
Metabolism
catabolism
anabolism
a set of reactions that extract biologically useful energy from the environment sources such as meat
a set of reactions that use this energy and small molecules derived from the breakdown of food to synthesize new biomolecules, supramolecular complexes and cells themselves
biochemical fuel generation is digestion
protein digested by protease secreted by stomach and pancreas
alpha-amylase from pancreas and lesser extent from saliva to degrade carb. to monosac.
lipids are converted to fatty acids by secreted by the pancreas
the low of pH of food stimulates the cells of the small intestine to release hormone "secretin"
polypeptide products of pepsin digestion stimulate the release of cholecystokinin (CCK) produced by intestinal cell
pancreas respond to CCK by releasing digestive enz. to the intestine
most end products; glucose, fructose and galactose
pancreastic enz. alpha-amylase cleaves the alpha-1,4 glycosidic bond of starch but not the alpha-1,6 bond.
lipids are ingested in the form of triacylglycerols and must be degraded to fatty acid for absorption across the intestinal epithelium
lipid form emulsion and the digested products form micelles
in the stomach convert lipids into an emulsion, mixture of lipid droplets and water
bile salts; emulsification- amphipathic molecules synthesized from cholesterol in the liver and secreted from the gall bladder
3 stages
large molecules are broken down into smaller units
various small molecules are further degraded to a few simple units that play a central role in metabolism, acetyl CoA
ATP is produced from the complete oxidation of acetyl CoA
basic principles that underlie in all living systems
fuels are degraded and large molecules are constructed step by step in a series of linked reaction called metabolic pathways
an E currency common to all life forms, ATP, links energy releasing pathways with energy-requiring pathways
the oxidation of C fuels powers the formation of ATP
although there are many metabolic pathways, a limited number of types of reactions and particular intermediates are common to many pathways
metabolic pathways are highly regulated to allow the efficient use of fuels and of coordinate biosynthetic processes
ATP is the universal currency of free energy
most of catabolism consists of reactions that extract E from fuels such as carb and fats and convert it into ATP
other nucleoside triphisphate are a senergy rich as ATP, ut the reasons that they are not used as the energy currency is unknown
ATP is an efficient energy currency because
electrostatic repulsion among phosphate groups in ATP
resonance stabilization if the inorganic phosphate is greater than do any of the phosphate in ATP
increase in entropy of the products
stabilization due to hydration, water bind to ADP and Pi, rendering the synthesis of ATP less favorable
metabolic pathways contain many recurring motifs
activated carriers of electron for fuel oxidation
activated carries of electron for the synthesis of biomolecular
activated carrier of to-carbon fragments
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