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by: Sydney Lazzell


Sydney Lazzell


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Study Guide of important lectures and flow chart of Chalk Talk
Human Physiology 1
Christopher DeSouza
Study Guide
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This 11 page Study Guide was uploaded by Sydney Lazzell on Friday September 30, 2016. The Study Guide belongs to IPHY 3470 at University of Colorado at Boulder taught by Christopher DeSouza in Fall 2016. Since its upload, it has received 338 views. For similar materials see Human Physiology 1 in integrated physiology at University of Colorado at Boulder.

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Date Created: 09/30/16
IPHY 3470: Exam 1 Study Guide Levels of Organization o Atoms – molecules – cells – tissues – organs – organ systems – organisms o Cells = containers of molecules that can sustain life o Tissues = collection of cells that work to achieve a common purpose/carry out related functions o Organs = group of tissues that carry out related functions o Organ systems = group of organs that integrate their functions o Endocrine = coordination of body function through synthesis & release of regulatory molecules  i.e. thryroid/adrenal gland o Immune = defense against foreign invaders  i.e. thymus, spleen, lymph nodes o Musculoskeletal = support & movement  i.e. skeletal muscles, bones o Nervous = coordination of body function through electrical signals & release of regulatory molecules  i.e. brain & spinal cord Homeostasis o A physiologically viable system that requires successful system responses to external/internal changes o Successful reestablished = homeostasis reestablished o Failure to compensate = pathophysiology (illness, death) The Cell 1. Cell membrane a. Phospholipid bilayer – polar hydrophilic head & nonpolar hydrophobic fatty acid tail b. More metabolically active = more increase in protein c. Protein & CHO give structure; role in self recognition & immune function d. Cholesterol & phospholipids provide the barrier 2. Nucleus a. Controls DNA, RNA, protein synthesis 3. Cytoplasm a. Cytosol b. Membranous organelles (2 membranes) i. Mitochondria = inner/outer membrane & matrix – produce ATP & can replicate ii. ER = smooth: lipids, steroids, fatty acids – rough: protein synthesis (ribosomes) iii. Golgi complex = protein packaging (protein from rough ER) & modification iv. Lysosomes = (came from Golgi) acidic pH, digestive enzymes, garbage disposals v. Peroxisomes = (came from ER) detoxifiers c. Inclusions (no membrane) i. Contact w/cytosol ii. Ribosomes = protein synthesis Cell Death o Necrosis = trauma, decrease in O2, toxins o Apoptosis = highly regulated programmed cell death o Protects cell growth/cell death (keeps the balance) o Caspase 3 Stem Cells 1. Totipotent = any cell type – any tissue – any organ a. After 4 days start to differentiate 2. Pluripotent = many but not all cell types – many but not all tissues or organs 3. Multipotent = source is bone marrow a. Most narrow in scope (e.x. EPC’s) Cell Metabolism 1. ATP: 1-3 sec Duration Activity 2. Creatine Phosphate: 5-15 sec 3. CHO metabolism: a. Anaerobic: 30 sec – 3 min b. Aerobic: <40 min 4. Fat metabolism: >40 min a. Slower but more ATP 5. Protein metabolism: no time line Intensity Activity Glycolytic Pathway (10 steps) Step 1: ATP ADP + H Glucose Glucose 6 Phosphate (G-6-P) o Enzyme = hexokinase (1 rate limiting step) Step 2: G-6-P Fructose 6 Phosphate o Enzyme = phosphohexoisomerase Step 3: ATP ADP + H F-6-P F1,6DP o Enzyme = PFK (2 ndrate limiting enzyme) Step 4: F1,6DP G3P & Dihydroxyacetone phosphate o Enzyme = aldolase Step 5: G3P Dihydroxyacetone phosphate o Enzyme = triose isomerase Step 6: NAD + Pi NADH + H2O G3P 1,3 –DPG o Enzyme = GAPDH o First “high energy” intermediate formation (NADH) o Used for lactate production or shuttles electrons o No NAD = glycolysis shuts down o Everything x2 from now on Step 7: ADP + H ATP 1,3- DPG 3-PG o Enzyme = phosphoglycerate kinase o First ATP generation Step 8: 3-PG 2-PG o Enzyme = phosphoglyceromutase Step 9: H2O 2-PG PEP o Enzyme = enolase Step 10: ADP + Pi ATP PEP Pyruvate rd o Enzyme = pyruvate kinase (3 rate limiting enzyme) o End of glycolysis Next step for Pyruvate: o Aerobic = further oxidized by citric acid cycle and goes to mitochondria o Anaerobic = always goes to lactate o Enzyme = LDH o NAD produced is recycled back to Step 6 *All enzymes are in the cytosol *Net ATP generated = 2 *HK, PFK, PK are most important enzymes – can only go in one downward direction CHO Metabolism o Normal glucose: 70-100mg/dL o Glycolysis = uptake of glucose from cells depends on several factors: o Type of tissue o Level of glucose in blood/tissue o Presence of insulin o Physiological state of tissue o Largest glucose consuming tissue = muscle o Lots of glucose = nerve & brain Glycolytic Flux 1. Allosteric control = affected by substrates, products, or co-enzymes a. PFK (+): ADP, AMP, F-6-P (low ATP state – flux through pathway is high) b. PFK (-): ATP, citrate, fatty acids (high ATP state – flux through pathway is low) 2. Covalent modification = phosphorylation or de- phosphorylation 3. Substrate cycles = HK, PFK, PK (thermodynamic in one direction) a. Balance between two enzymes 4. Genetic control = long time Glycogenolysis o Storage form of CHO in the body is glycogen o Muscle = gluco-utilizing o Liver = gluconeogenic o Enzymes: o Glycogen phosphorylase = breaks C1-C4 bond  (+): AMP  Ca2+  (-): ATP, G6P, glucose o Glycogen debranching enzyme = breaks C1-C6 bond, allowing the glycogen phosphorylase to go to completion o Phosphoglucomutase = coverts G1P to G6P (goes down pathway) Gluconeogenesis o Occurs to help maintain blood glucose levels o Liver & kidney o Substrates: pyruvate, lactate, Krebs cycle intermediates o Most important source = MUSCLE o Need to bypass 3 enzymes: o PK: enzyme 1 = pyruvate carboxylase, enzyme 2 = PEP carboxykinase o PFK: enzyme = fructose bisphosphatase o HK: enzyme = glucose-6-phosphatase Krebs Cycle o Pyruvate  Acetyl-CoA Enzyme = pyruvate dehydrogenase o ATP high = pyruvate dehydrogenase activity low o 3 NADH, 1 FADH2, 1 GTP o 6 NADH, 2 FADH2, 2 GTP in 1 glucose molecule o 4 regulatory sites (enzymes): o Pyruvate  Acetyl-CoA o Citrate synthesis o Isocitrate DH o a-Keto DH o Regulators: o Substrate availability o Product inhibition o Ca2+ o PDH o (-): Acetyl-CoA, NADH o (+): Ca2+, AMP o CS o (-): NADH, Succinyl CoA, Citrate o (+): Ca2+, Acetyl-CoA o Iso DH o (-): NADH, ATP o (+): Ca2+, ADP o a-Keto DH o (-): NADH, Succinyl CoA o (+): Ca2+ o 2 shuttle systems: o malate-aspartate (heart)  (cytosol) NADH --- (mitochondria) NADH = 3 ATP o glycerol-phosphate (muscle)  (cytosol) NADH --- (mitochondria) FADH2 = 2 ATP ETC o Although most of the NADH generated by glucose oxidation is formed in the mitochondria matrix via the Krebs cycle, NADH generated by glycolysis occurs in the cytosol o 4 complexes o NADH comes in complex 1, goes through 3 & 4 = 3 ATP o FADH2 comes in complex 2 (no ATP), goes through 3 & 4 = 2 ATP o 2 enzymes: CoQ & cytochrome C o Location: inner membrane of mitochondria o Net release for 1 glucose = 38 ATP o McArdle Syndrome = inability to break down glycogen o Caused by a defect in a gene that makes glycogen phosphorylase (breaks C1-C4 bond), patients cant cleave that bond = no glygogenolysis Lipid Metabolism o Triglycerides (TG) = 90% of dietary lipids – what we are breaking down when talking about lipid metabolism o Glycerol backbone & fatty acids tails o HSL (hormone sensitive lipase) cleaves off fatty acid tails from backbone  (-): insulin  (+): catecholamines & growth hormones o Sources = adipose tissue & diet o Esterification = making TG o Lipolysis = process of TG hydrolysis o Fats are important for prolonged work, small increase in fat utilization can reduce CHO o To get fatty acids from cytosol to mitochondria = Carnitine Shuttle Beta Oxidation o Each time around: kick off 2 carbons, 1FADH2, 1 NADH, 1 Acetyl-CoA o Last product = Acetyl-CoA o Yield = 1 NADH, 1 FADH2, 1 Acetyl-CoA Glucose Fatty Acid Cycle o 3 enzymes: o PFK (-): ATP, citrate o HK (-): G-6-P o PDH (-): Acetyl-CoA o Crossover effect: o As aerobic power increases (up to 100%), fat % decreases and CHO % increases o Endurance athletes = can move the crossover mark to the right to go longer at a higher intensity while burning and relying on fat  They can increase their mitochondria count Effect Lipid Utilization o Heart & liver adapt for lipid utilization – heart = fat o Brain % red blood cells rely on glycolysis – brain = CHO Protein Metabolism o Essential amino acids = diet o Nonessential amino acids = made naturally o Amino acids divided into 2 groups: o 1. Glucogenic = glucose o 2. Ketogenic = fatty acids or ketones o Need to get rid of 2 amine groups to turn into either Krebs or glycolytic intermediates o Transamination o Oxidative deamination 1. a.a. + a-Ket (transaminase) a-Keto acid + glutamate pyruvate + glutamate alanine + a-Keto a. Muscle moves left to right due to increase in pyruvate & glutamate = release of alanine (wants ATP from Krebs intermediate) b. Liver moves right to left as alanine is used to produce pyruvate = glucose (gluconeogenesis) 2. Enzyme = glutamate dehydrogenase yielding ammonia or a-Keto Ketones as Fuel o Rely under starvation/prolonged exercise/diabetes o In the liver o Converted to: o Acetoacetate o B-hydroxylbuterate o Acetate o Released into circulation for uptake by BRAIN & NERVES


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