Biolchem 415 1st EditionExam # 2 Study Guide Lectures: 11 - 21Lecture 11 (February 6)Give a brief explanation of signal transduction.- First there is a primary signal (first messenger) that can be a hormone or neurotransmitter etc. This interacts with a specific membrane receptor. This receptor complex at the membrane transduces the signal and generates intracellular second messengers and/or active protein kinases. This amplifies the relay of the signal. Intracellular effector proteins that mediate the physiological response are then activated or inhibited. Explain 7TM receptors- 7TM receptors are receptor proteins that transmit signals and are G-Protein coupled receptors (GPCRs). The binding site for the ligand lies near the extracellular surface. A diverse array of signals act on these receptors then they act as second messengers to relay the signals to intracellular targets. A ligand such as epinephrine will bind to the receptor leading to a conformational change and then activation of heterotrimeric G proteins. Which property of signaling cascades allows them to act as potent signal amplifiers? Give an example explanation of a cascade. - Activated enzymes act as catalysts, converting many substrates to products. A transmembranesignal can trigger a cascade. For the first amplification a single ligand receptor complex can stimulate the activation of many G proteins. This leads to the second amplification as the β,γ subunits leave the GDP and GTP activates a adenylate cyclase which in turn catalyzes the synthesis of many cAMP. After this the cyclic AMP activates protein kinase A which can then phosphorylate many target proteins. What are the two possible ways for signal termination of occur?- The ligand can dissociate. This is a reversible binding and decreasing levels of hormone in the circulation can lead to this dissociation. Second the termination can be caused by spontaneous hydrolysis of GTP by intrinsic GTPase activity of Gα. In this case the Gα has phosphorylated from GTP to GDP and then reassociates with the βγ-subunits forming the inactive heterotrimer and releases the target enzyme. Why is Ca2+ an important second messenger?- Calcium is versatile resulting in its widespread and efficient use as a second messenger. It is present at very low steady state levels in all cells and small changes in these levels can be sensedby calcium-sensitive proteins. The protein calmodulin can bind resulting in a complex that can act as a diffusible allosteric effector for a wide variety of enzymes, pumps and other target proteins. How is insulin signaling terminated?- First the ligand can dissociate from the receptor. This can lead to the reversal of phosphorylations by hydrolysis. 2 – the protein tyrosine phosphatases which dephosphorylates the receptor. 3 – the protein ser/thr phosphatases which can dephosphorylate Akt, etc. 4 – the lipid phosphatases which can dephosphorylate PIP3.How do the mechanisms of action of cholera and pertussis toxins contribute to the activation of Protein Kinase A?- ADP-ribosylation of Gαi versus Gαs subunits of different G-proteins. The cholera toxin modifies the G-protein to Gαs so that it remains in a permanent on state. This means that adenylase cyclase and protein kinase A will be continually activated. This leads to a dysregulation of ion movement resulting in massive loss of NaCl and water leading to dehydration leading to death. The pertussis toxin modifies the G-protein to Gαi so that it remains in a permanent off state. Thisprevents the exchange of GDP to GTP and Gαi can no longer inhibit adenylate cyclase so it remains active. This leads to increased levels of cAMP and phosphorylations. Regulation of calcium and potassium channels is affected. What dysregulation can lead to cancer and what are some ways of treating cancer?- The dysregulation of EGF signaling can lead to cancer. Protein kinase inhibitors can be used as anticancer drugs.Lecture 12 (February 9) What are monosaccharides? Give some examples. - Monosaccharides exist in isomeric forms and are aldehydes or ketones that have two or more alcohol groups. The smallest possible ones have three carbons. They can exist in both open and cyclic forms. The linear form is called a “Fisher projection” and the cyclic forms are “Haworth projections”. Some examples of monosaccharides are D-ribose, D-deoxyribose, D-glucose, D-Mannose, D- Galactose, and D-Fructose.Discuss Oligosaccharides, Polysaccharides, and complex carbohydrates and how they are different.- Oligosaccharides contain two or more monosaccharides linked by O-glycosidic bonds. These can’t be broken down easily and can’t go into metabolism. Instead they are cleaved by enzymes on the outer surface of the intestinal epithelium. Polysaccharides can be more easily broken down and are used as energy storage (glycogen and starch). They are linked by α-glycosidic bonds. Complex carbohydrates are proteins and carbohydrates linked together that create multifaceted polymers. The carbs can be N-linked to protein side chains of asparagine or O-linked to serine or threonine. Complex carbohydrates can be glycoproteins (sugars attached to proteins), proteoglycans (large proportion of polysaccharides in the structure), or mucoproteins (glycoproteins with amino-sugar content). How do surface carbohydrates affect toxin/virus attacks?- Carbohydrate moieties of glycolipids and glycoproteins on the surface of the plasma membraneare often used as initial binding sites for toxin and virus attacks. What are the three stages of generating energy from food?1) Digestion – this is the process of breaking large molecules into smaller molecules2) Metabolism – the small molecules are processed into key molecules of metabolism (ex: acetyl CoA)3) Energy – ATP is produced from the complete oxidation of the acetyl component of acetyl CoAThe purpose of bile salts is to…- emulsify dietary lipids to make the lipids more accessible to intestinal lipases.What do proteases do and how do they do this?- Proteases digest proteins into amino acids and peptides. First components of the digestive pathways are secreted by the small intestine, pancreas, and gall bladder. These components are secretin (causes release of sodium bicarbonate, neutralizing stomach acid) and Cholecystokinin ((CCK) stimulates release of digestive enzymes from pancreas and bile salts from gall bladder). Inactive enzymes secreted from stomach/pancreas (zymogens) are