BMB 462 Lecture 8 Outline of Last Lecture I. Continued Analysis of the Beta-Adrenergic Receptora. Review of Structureb. Mechanismc. TerminationII. Different Signal Transduction CascadesIII. G Protein InhibitorsIV. Multivalent ProteinsV. Insulin Regulation of Gene ExpressionOutline of Current Lecture I. Neuronal SignalingII. Regulation of Transcription by Steroid Hormone ReceptorsIII. Energy Catabolism in the 4 basic biochemical building blocksIV. Energy storage in lipidsV. Lipid digestion, absorption, and transport in mammalsVI. Mobilization of Triacylglycerol from adipose tissueVII. Glycerol MetabolismVIII. Fatty Acid CatabolismCurrent LectureConcepts to remembers from previous courses/lectures:- Glycolysis- Thioester bonds are high energy bonds- Citric acid cycle- G protein-coupled receptors- Receptor Tyrosine kinasesI. Neuronal Signaling (an example of a system using Gated Channels)a. Membrane depolarization (signal)These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.i. The initial signal for a voltage gated signal; it results in a conformational changeb. Voltage Gated Ion channel (receptor)i. As the membrane depolarizes, the channel has a conformational change1. The change allows ions to flow throughc. Ca2+ (2nd messenger)i. Ca2+ enters at the terminal of the axon and interacts with other proteins, causing vesicles to fuse with the membrane and release neurotransmittersd. Cellular Response – The release of neurotransmittersi. To continue the cycle through to the next neuron, the cell needs a second receptor. The 2nd one is a ligand gated transporter and the signal is a neurotransmitter (i.e. acetylcholine)1. The signal binds to the receptor, causing a conformational change2. The change causes membrane depolarization to open the next set of gated channels and carry on the signale. The Voltage Gated Ion Channel has a number of positively charged residues (i.e. Lysine and arginine) which interact with the negative inside of the channeli. This interaction pulls the positive residues in so that the gate is closedii. Depolarization reduces the pull on the positive residues so that the helices swing open and open the channel for ion flowf. Ligand Gated Channels have helices in a certain conformation which gets rotated when the signal is boundi. The polar residues move in while the bulky hydrophobic residues that were originally blocking the channel opening move to the outsideii. The now-polar channel is selective for what it lets throughII. Regulation of Transcription by Steroid Hormone Receptorsa. Steroid hormone receptors (SHR) – some SHRs do sit on the plasma membrane and bind with hormones on the membrane, acting as G protein-coupled receptors or Receptor tyrosine kinasesi. BUT this is rareii. The classic, stereotypical SHR is not an integral protein; instead it sits in the cell (in the cytosol or the nucleus) so the signal has to cross the membrane to reach itb. Steroid Hormone (signal)i. It’s hydrophobic so it can cross the membrane to enter the cell and bind to the receptor1. Thyroid hormones are polar, though, so they need a transporterii. The first signal gets inside the cell to bindiii. The hormone is a slow acting signal – it takes time to bind to DNA, changethe gene expression, and then the mRNA has to be made and translated to have a new protein that performs different functionsc. Receptor/Transcription Factori. It has one domain to bind the signalii. A second domain acts as a transcription factor to change gene expressiond. Cellular response – is a change in gene expressioni. There isn’t much signal transduction because there is only one component (the receptor) that also acts as the effector by binding to DNAand changing it’s expressionIII. Signal transduction speed changes according to the goala. Changing gene expression is slow (it can take hours or days because it takes time to rearrange the DNAb. Effecting a protein that’s already there happens much faster (i.e. epinephrine/adrenaline signaling)c. Be able to apply details of these specific examples to unknown, general examplesi. You should be able to reconstruct a mechanism/understand what’s going on- Beginning of unit on Lipid Catabolism - IV. Energy Catabolism in the 4 basic biochemical building blocksa. Nucleotides – have no energy storage and break down does not provide energyi. This is because nucleic acids are the most important molecules for long term survival of the cell, because they contain the genetic information, soit doesn’t make sense to break them down for energyb. Amino Acids – No specific storage form in humans, though the body will start breaking down muscle for energy in starvation situationsi. Energy stored as protein is about 17 kJ/gc. Monosaccharides – are stored as glycogen, which is hydratedi. This is a short term, quick energy storage (usually only 24 hours worth of energy is stored as carbohydrates)ii. Energy stored as a carbohydrate is about 16 kJ/giii. Amino acids and monosaccharides are more oxidized than the carbons in lipids, so they don’t provide as much energy when broken downd. Fatty Acids – are stored in anhydrous lipid droplets (the droplets do not associate with water)i. The body can extract the most energy from lipids because they are the most saturated1. You extract energy via oxidation; the more reduced the molecule, the more energy there is to remove and generate by moving the electrons through the Electron Transport Chainii. There is about 1-3 months worth of energy stored as lipidsiii. Energy stored as lipids is about 18 kJ/giv. It is significantly heavier to store the same amount of energy as carbohydrates instead of lipids1. Evolutionarily speaking, for animals that need to run to survive, this doesn’t make senseV. Energy Storage in Lipidsa. It is more efficientb. Oxidation state of the carbons – very reducedc. Storage Form – stored anhydrousd. Chemical reactivity – esterified bonds are very non-reactive, so the cells don’t have to worry about accidental chemical reactions causing problems for the cellVI. Lipid digestion, absorption, and transport in mammalsa. There are issues with hydrophobicity – breaking down lipids to store it as energyi. It has to be digested and transported to the intestines but lipids clump up when they are in aqueous solution1. This is a problem because proteins need to be able to access the fatty
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