Aherns Biochemistry 18 Carbohydrates amp Signaling











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1. Contact me at [email protected] / Friend me on Facebook (kevin.g.ahern) • 2. My lectures with The Great Courses - https://www.thegreatcourses.com/cours... • 3. My Lecturio videos for medical students - https://www.lecturio.com/medical-cour... • 4. Course materials at http://davincipress.com/bb450.html • 5. Take my free iTunes U course at https://itunes.apple.com/us/course/bi... • 6. Course video channel at http://www.youtube.com/user/oharow/vi... • 7. Check out all of my free workshops at http://davincipress.com/freebies.html • 8. Check out my Metabolic Melodies at http://www.davincipress.com/ • 9. My courses can be taken for credit (wherever you live) via OSU's ecampus. For details, see http://ecampus.oregonstate.edu/soc/ec... • 10. Download my free biochemistry book at http://www.davincipress.com/freeforal... • • 1. Glycoproteins consist of a protein linked to an oligosaccharide, via an 'N' or an 'O' linkage. N linkages occur through asparagines. O linkages involve serine or threonine. • 2. Oligosaccharides on proteins (glycoproteins) and lipids function in cellular identity. • 3. A,B, and O blood group antigens arise from carbohydrates on their cell surfaces distinguish the various blood types. • 4. N-linked glycoproteins have glycosylation occurring in the endoplamic reticulum and Golgi complex of the cell. O-linked glycoproteins have glycosylation only in the Golgi complex. • 5. Oligosaccharides destined to be linked to proteins are built on dolichol phosphate on the outer portion of the endoplasmic reticulum and then this flips to the inside for attachment. • 6. Specific carbohydrate residues on the surface glycoproteins of blood cells are binding targets for hemagluttanin proteins on the surface of flu viruses. To exit a cell, the virus must cleave sialic acid off with a neuraminidase enzyme. Tamiflu acts by inhibiting the neuraminidase. • Signaling Highlights • 1. Signaling involves a first messenger which is released by one cell of the body, travels through the bloodstream, and interacts with a receptor on another cell of the body. • 2. When a cell's receptor binds to a hormone, it initiates events inside of cells that communicate the signal and this results in changes inside of the cell. Frequently, this involves a second messenger, which is made or released inside of the target cell. • 3. The beta-adrenergic receptor works as follows. Epinephrine (adrenalin) is released into the bloodstream in response to a stimulus. This molecule is the first messenger. When it arrives at the target cell, it binds to receptor, causing it to change shape. On the inside of the cell, the receptor acts on a G protein to activate it. The activated G protein stimulates adenylate cyclase to synthesize cAMP. cAMP is a second messenger, which binds to Protein Kinase A (PKA) to activate it. Activated PKA begins phosphorylating a set of enzymes, turning them on or off (depending on the enzyme). • 4. Phosphorylation of transcription factors can activate or inactivate them. When activated they will turn on production of specific genes in the DNA. • 5. Receptors of the first messenger have similarity in structure, consisting of a polypeptide chain that spans the cell membrane 7 times. Such proteins are called 7TM proteins. • 6. G proteins bind guanine nucleotides. G protein complexes have three subunits - alpha, beta, gamma. The alpha subunit binds to GDP or GTP. When the alpha subunit is bound to GDP, it also binds the beta and gamma subunits. The G protein complex is thus inactivated. When the beta-adrenergic receptor binds its ligand, it stimulates the 'loading' of GTP onto the alpha subunit, displacing GDP in the process. On binding GTP, the alpha subunit dissociates from the beta and gamma units. The alpha subunit is then free to bind other target proteins and is thus 'active' when bound to GTP. • 7. G proteins slowly break down GTP to GDP. This activity is very important because it ensures that the G protein will not be left in the 'on' state permanently. When the alpha subunit is bound with GTP, it can bind to adenylate cyclase (an enzyme embedded in the cell membrane) and activate it. When the alpha subunit has GDP, it is bound with the beta/gamma subunits and CANNOT bind to adenylate cyclase. • 8. cAMP in cells acts on Protein Kinase A (PKA). PKA has two identical catalytic subunits (C) and two identical regulatory subunits (R). When present as C2R2, the PKA is inactive. Binding of cAMP to the R subunits causes them to dissociate from the C subunits, activating them. • 9. Signaling through the adrenergic receptor increases blood glucose. Insulin is a hormone that counters the effect of epinephrine. Increasing cAMP in liver cells increases blood glucose. Phosphodiesterase breaks down cAMP. Inhibitors of phosphodiesterase, such as caffeine, have the effect of increasing blood glucose.

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