BMB 462 Lecture 8 Outline of Last Lecture I Continued Analysis of the Beta Adrenergic Receptor a Review of Structure b Mechanism c Termination II Different Signal Transduction Cascades III G Protein Inhibitors IV Multivalent Proteins V Insulin Regulation of Gene Expression Outline of Current Lecture I Neuronal Signaling II Regulation of Transcription by Steroid Hormone Receptors III Energy Catabolism in the 4 basic biochemical building blocks IV Energy storage in lipids V Lipid digestion absorption and transport in mammals VI Mobilization of Triacylglycerol from adipose tissue VII Glycerol Metabolism VIII Fatty Acid Catabolism Current Lecture Concepts to remembers from previous courses lectures Glycolysis Thioester bonds are high energy bonds Citric acid cycle G protein coupled receptors Receptor Tyrosine kinases I 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 change b Voltage Gated Ion channel receptor i As the membrane depolarizes the channel has a conformational change 1 The change allows ions to flow through c 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 neurotransmitters d Cellular Response The release of neurotransmitters i 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 change 2 The change causes membrane depolarization to open the next set of gated channels and carry on the signal e 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 channel i This interaction pulls the positive residues in so that the gate is closed ii Depolarization reduces the pull on the positive residues so that the helices swing open and open the channel for ion flow f Ligand Gated Channels have helices in a certain conformation which gets rotated when the signal is bound i The polar residues move in while the bulky hydrophobic residues that were originally blocking the channel opening move to the outside ii The now polar channel is selective for what it lets through II Regulation of Transcription by Steroid Hormone Receptors a 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 kinases i BUT this is rare ii 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 it b Steroid Hormone signal i It s hydrophobic so it can cross the membrane to enter the cell and bind to the receptor 1 Thyroid hormones are polar though so they need a transporter ii The first signal gets inside the cell to bind iii The hormone is a slow acting signal it takes time to bind to DNA change the gene expression and then the mRNA has to be made and translated to have a new protein that performs different functions c Receptor Transcription Factor i It has one domain to bind the signal ii A second domain acts as a transcription factor to change gene expression d Cellular response is a change in gene expression i There isn t much signal transduction because there is only one component the receptor that also acts as the effector by binding to DNA and changing it s expression III Signal transduction speed changes according to the goal a Changing gene expression is slow it can take hours or days because it takes time to rearrange the DNA b 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 examples i 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 blocks a Nucleotides have no energy storage and break down does not provide energy i This is because nucleic acids are the most important molecules for long term survival of the cell because they contain the genetic information so it doesn t make sense to break them down for energy b Amino Acids No specific storage form in humans though the body will start breaking down muscle for energy in starvation situations i Energy stored as protein is about 17 kJ g c Monosaccharides are stored as glycogen which is hydrated i 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 g iii Amino acids and monosaccharides are more oxidized than the carbons in lipids so they don t provide as much energy when broken down d 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 saturated 1 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 Chain ii There is about 1 3 months worth of energy stored as lipids iii Energy stored as lipids is about 18 kJ g iv It is significantly heavier to store the same amount of energy as carbohydrates instead of lipids 1 Evolutionarily speaking for animals that need to run to survive this doesn t make sense V Energy Storage in Lipids a It is more efficient b Oxidation state of the carbons very reduced c Storage Form stored anhydrous d Chemical reactivity esterified bonds are very non reactive so the cells don t have to worry about accidental chemical reactions causing problems for the cell VI Lipid digestion absorption and transport in mammals a There are issues with hydrophobicity breaking down lipids to store it as energy i It has to be digested and transported to the intestines but lipids clump up when they are in aqueous solution 1 This is a problem because proteins need to be able to access the fatty acids to break them down and absorb the fatty acids lipids b Bile salts these are cholesterol derivatives that are made more polar and can
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