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MIDTERM 2 REVIEW NOTES (all important information for midterm) - LIFESCI 2N03
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Department
Life Sciences
Course
LIFESCI 2N03
Professor
Danny M.Pincivero
Semester
Fall

Description
Midterm 2 LIFESCI 2N03 Quicknotes November 18, 2013 Bioenergetics  Metabolism – sum of all chemical reactions that occur in the body o Anabolic reactions – synthesis of molecules o Catabolic reactions – breakdown of molecules o Bioenergetics – converting glucose, protein and lipids into energy Eukaryotic Cells  Organelles – nucleus( closed compartment that contains DNA ), mitochondrion (ATP production), cellular membrane (cellular electricity (Na+/K+, electrical potential), intracellular signaling)  Protein synthesis o Transcription (DNA (contains information to make proteins) transcribed to produce mRNA)  mRNA leaves nucleus and binds ribosome  translation (AA carried to ribosome by tRNA; mRNA determines arrangement of AA in polypeptide chain) o Exercise, dietary amino acids, anabolic steroids – can begin process  Reactions o Endergonic – require energy; endothermic o Exergonic – release energy (transfer to mechanical, chemical, thermal); exothermic o Oxidation – removing an electron (or H, which contains e NADH (reducing agent; becomes oxidized) o Reduction – adding an electron (or H, which contains e ) NAH (oxidizing agent; becomes reduced) Enzymes  Enzymes – catalysts that regulate speed of reactions; lower the activation energy  Temperature and pH affect enzyme ability – must be regulated for optimal range o Normal body temperature 37˚C; body temperature during exercise (40˚C); enzymes can denature at too high temperatures o Optimal pH range for enzyme activity ~7.5-8 Energy  Energy “substrates” – carbohydrates, fats, proteins – from diet and storage (liver, glucose; muscle, protein)  Muscle cell – ATPase binds to ATP and expends energy o Myosin ATPase – for force production; contractile muscle and enzyme; can bind ATP and harness energy; o SERCA (sarco endoplasmic reticulum calci– return calcium after muscle contraction or keep muscle rested o Na+/K+ ATPase – keep muscle from contracting uncontrollably  Energy production from substrates depend on – i) substrate availability ii) enzyme dyn(pH, temperature, exerciii) nervous system demand (NS activated to activatemuscle tiv) metabolic backup(maximal usage of glucose; shift to different substrate)  When phosphate is removed from ATP, chemical energy is harnessed to convert to mechanical energy and thermal energy (60-70%)  Formation of ATP – o Anaerobic (rapid, enzyms in cytoplasm) – PCr breakdown, degradation of glucose (glycolysis) o Aerobic (enzymes in mitochondria) – oxidative phosphorylation (glucose > fat > protein) Creatine  Non-essential; found in meat and fish  Found primarily in skeletal muscle, heart, spermatozoa, retinal cells  2 step process (humans) o Kidney Arginine + Glycine ---AGAT---> Guanidinoacetate + Ornithine  AGAT = arginine:glycine amidinotransferase  Arginine made from citruline; glycine made from serine (conditionally essential) o Liver Guanidinoacetate + Methionine ---GAMT---> Creatine + Homocysteine  Methionine( essential; eggs, meat, fish, sesame seeds, cereal grains)  Creatine phosphate (PCr) used to synthesize ATP for high intensity/velocity muscle contraction – PCr contains energy in phosphate bond o PCr + ADP ATP + Cr (reverse reaction occurs if the need for energy decreases; rest)  Creatine kinase = 381 aa sequence  Rapid production of ATP – only 1 reaction from PCr to ATP (compare to 15 reactions in glycolysis to produce ATP)  expended quickly o Eg/ Knee Exterior Muscle Cell – sarcomere (muscle contractile protein; contract, relax, interact = movement and force generated)  Eg/ Muscle [phosphocreatine] dynamics following the onset of exercise in humans; influence of baseline workout rate o Experiment – 7 healthy men (sprinters, weight lifters; high intensity maximal muscle fibre recruitment); single leg knee extensions  Moderate – 40% highest work rate, 6 min; Heavy – 80% highest work rate, 6 mins o PCr at resting level (100%) at onset of exercise; burn PCr until 60% of resting value, then stabilizes  begins using other macronutrients  PCr begins workout; plateaus around 41 s  Supplementation – increase muscle stores of PCr; extends high intensity exercise and speeds muscle recovery o Supplements  Types – creatine monohydrate, creating anhydrous, creatine phosphate, creatine-O-phosphate  Forms – creatine monohydrate (holds one 2 O molecule); creatine anhydrous (more concentrated by drying monohydrate at 100˚C); creatine salts (combining creatine and strong acid (pyruvic acid, malic acid, citric acid)  Content – creatine anhydrous (100%), creatine monohydrate (88%), creatine malate (75%), creatine citrate (66%)  Stability – creatine monohydrate most stable (longest shelf life); degrades in warm, acidic water (must be consumed immediately after dissolving)  Creatine salts more soluble than creatine monohydrate o Bioavailability – absorb creatine from small intestine into blood; uptake creatine into muscle tissue 1 Midterm 2 LIFESCI 2N03  Dietary creatine – ~100% intestinal absorption  Muscle tissue uptake stimulated by insulin o Eg/ Analysis of the efficacy, safety and regulatory status of novel forms of creatine – after 3 days supplementation, observe retention of creatine  Body retained creatine monohydrate dissolved in glucose solution better than creatine dissolved in water o Creatine dosage – takes 2-3 days for tissue creatine accumulation  Loading Phase – first 4-6 days (4, 5 g servings); bombard muscle tissue with PCr  Maintenance Phase – 5g/day o 5-20% improvement in short-term exercise (cycling, sprinting, jumping, resistance) o Side effects – i) increased weight gain (muscle water retention) ii) nausea, vomiting, diarrhea with exercise iii) increased urinary creatine and creatinine causing kidney inflammation (suspected; kidney must filter more) iv) altered fluid balance (may predispose to dehydration) v) negative feedback from exogenous supply; decreases natural production o Eg/ Influences of dietary creatine supplementation on muscle phosphocreatine kinetics during knee-extensor exercise in humans  Experiment – 7 healthy men (sprinters, weight lifters; high intensity maximal muscle fibre recruitment); single leg knee extensions  Moderate – 40% highest work rate, 6 min; Heavy – 80% highest work rate, 6 mins  Exercise performed prior and following creatine monohydrate supplementations; 10g/day; 5-10 days  Results  Resting and exercise PCr levels – heavy exercise; supplementation allowed for greater amount of PCr throughout exercise, took longer to deplete PCr  Exercise and recovery time constraints – greater residual creatine in supplemented muscle; same rate of recovery for both groups Carbohydrates  Glucose - broken down by glycolysis; neurons and RBCs can only use glucose  Fructose – passes through liver and broken down  50% glucose; 25% lactate (reduces pH); minor amounts VLDL  Glycogen – storage form of glucose in liver and muscle; synthesized by glycogen synthase; broken down by glycogenolysis o Cleaved into glucose units  Muscle – myophosphorylase (activated by epinephrine); followed by phosphoglucomutase (saves 1 ATP)  exercise stimulates sympathetic NS activation and epinephrine secretion to start glycogen breakdown  Liver – phosphorylase (activated by glucagon from pancreas); followed by glucose-6-phosphatase (allows glucose to enter blood)  Glycolysis (begins at glucose)/Glycogenolysis (begins at glycogen) (Embden-Meyerhof Pathway) – aerobic and anaerobic pathway to re- synthesize ATP; cytoplasm o Pathway – trap glucose in cell; make it unstable  Glucose + ATP ---hexokinase---> Glucose-6-Phoshate + ADP (2 ATP spent)  Glucose (6C) 2 (Pyruvate (3C)+ NADH + H + 2 ATP) + o Metabolic Yield – 4 substrate level ATP (gross); 2 NADH + H (reducing equivalents); 2 pyruvic acid (and lactic acid) o Metabolic Cost – 1 ATP (muscle glycogen)/2 ATP (muscle glucose); 2 NAD  Krebs Cycle/TCA/Citric Acid Pathway – anaerobic; mitochondria o Pathway  Pyruvate (3C)---dehydrogenase (PDH)---> Acetyl CoA (2C)+ CO2  Acetyl CoA (2C) Citric Acid(6C) Oxaloacetate (4C) ----------------> Acetyl(2C) (cycle) o Yield – 1 ATP, 2 CO , 3 NADH + H , 1 FADH (note: NADH + H used in pyruvate conversion) o Cost – Pyruvate  Oxidative Phosphorylation – mitochondria (on inner membrane) o Yield – 2 ATP per FADH 2 3 ATP per NADH + H  3 NADH + H = 9 ATP; 1 FADH = 2 AT2; 1 ATP bonus  12 ATP total (per Kreb Cycle) x 2 pyruvate  24 ATP o Cost – NADH + H + FADH , O 2 2 Lipids  Adipose Site – fat cell; fat droplet contains triglycerides (3 fatty aids attached to glycerol backbone)  Triglyceride must move from fat cell to CV to muscle cell for it to be catabolized 1. Mobilization – fatty acid to CV; receptors of fat cell sensitive to external signals  Epinephrine (adrenal gland) – binds receptor and activates TG Lipase (uses fat for energy); secreted with sympathetic NS  Insulin (pancreas) – binds receptor and deactivates TG Lipase; secreted in response to elevated [blood glucose] (ingestion of sugar causes cells to store fat) 2. Activation – fatty acid attaches to mitochondria; muscle cell  Carnitine – amino acid that binds fatty acid and makes it unstable 3. Beta-Oxidation - -carbon removed from fatty acid and can convert it to Acetyl Co(2C); muscle cells  H3C-C-C-C-C-COOH  methyl, 1, 2, beta carbon, alpha carbon, carboxyl  Roles o Building blocks of phospholipids and glycolipids o Protein modification by attaching to fatty acids o Fuel o Derivatives serve as hormones and intracellular messengers Protein  Amino acids (20 total) assembled in various combinations in 4 levels of structure (1˚, 2˚, 3˚, 4˚)  Gluconeogenesis – liver cells convert amino acids from muscle tissue to glucose; occurs in very low carb diet or long duration exercise 2 Midterm 2 LIFESCI 2N03  Conversion to metabolic intermediates Energy Expenditure  Energy expenditure based on exercise duration and type – aerobic can use fats, proteins carbs to make ATP; anaerobic can only use glucose  Incremental Exercise – Oxygen uptake (VO 2;xygen intake per uni) increases linearly with work rate(intensity, not duruntil maximal oxygen uptake (V2 max, then begins anaerobic pathways to increase work rate o VO 2ax – maximum ability of cardiorespiratory system to deliver oxygen to muscles (limited by RBC); ability of muscle to use oxygen and produce ATP aerobically (limited by mitochondria); affected by genetics and training; quantified in L/min  Lactate Threshold o Lactate production - +  Glucose (6C) 2 GA-3-P (3C)+ e + H  2 Pyruvate (2C)  LDH (enzyme in cytoplasm) binds NADH + H + pyruvate  NAD + lactic acid (dissociates into lactate + H ; reduced pH)  Occurs when NADH + H is not used to make ATP immediately in oxidative phosphorylation  Advantage – can make more pyruvate (thus make more ATP)  Disadvantage - lactic acid leads to muscle fatigue; slows muscle ability to use energy and produce force; sensitive pain neurons o Abrupt (non-linear) increase in blood lactate – low intensity slow increase; reach critical exercise level lactate level rises quickly o Lactate threshold ~50-60% VO max in untrained subjects; higher lactate threshold (50-80%) in trained subjects 2 o Reasons for lactate threshold  Low muscle oxygen (hypoxia) – less active mitochondria  Accelerated glycolysis – NADH produced faster than used; excess in cytoplasm not being used in mitochondria  Recruitment of fast twitch muscle fibers – LDH isozyme in FT fibers promote lactic acid formation; ST more mitochondria  Reduced rate of lactate removal from blood – reduced blood vessels to muscle causing lactate to be trapped in hypoxic muscle cell; lactate accumulates, pathway slows Fuel Selection and Exercise  Low intensity exercise (<30% VO 2ax) – fats are primary fuel; using fuel source stored in higher abundance  High intensity exercise (>70% VO 2ax) – carbohydrates primary fuel  “Crossover concept” – shift from fat to carbohydrate metabolism as exercise intensity increases  Due to – i) recruitment of fast muscle fibers at higher intensity ii) increasing blood levels of epinephrine  Prolonged low-intensity exercise – shift from carbohydrate to fat metabolism due to increased rate of lipolysis; stimulates by rise in blood level epinephrine; reflexive mechanism o Triglycerides ---lipases---> glycerol + FFA Carbohydrates  Carbohydrate – hydrate of carbon; manufactured by plants  Glucose: 6 CO + 6 H O + Energy  C H O + 6 O 2 2 6 12 6 2  Glucose storage forms o Glycogen (animals) – 8-10 glucose units then branch o Starch (plants) – i) amylopectin (makes up ¾ of starch; 25-30 glucose units then branch) ii) amylos(1/4 starch; more compact)  Mouth; mechanical digestion, moisten, chemical digestion (salivary amylase; starch -> small polysaccharides)  stomach (inactivates salivary enzymes)  intestines (amylase through pancreatic duct from pancreas starch -> small polysaccharides; maltase, sucrose, lactase from small intestine cells hydrolyze disaccharides to monosaccharide’s)  Fiber (plants) – non-digestible carbohydrates; holds water, regulates bowel activity, binds and carries substances (cholesterol, bile) out of body o Soluble – dissolves in hot water; forms gel in GI system --> slows gastric/intestinal motility, absorbs FA’s, fuller feeling --> decreases CV disease (less cholesterol absorbed into body)  Eg/ Oat, bran, dried beans, nuts  Mouth; mechanical digestion, moisten  stomach (no digestion, slows motility)  small intestine (no digestion, slows absorption)  large intestine (fermentation, small amount becomes short chain FA’s, gas) o Insoluble – does not dissolve; absorbs water in GI system, speeds intestinal motility; decreases Type II DM; can lead to nutrient deficiencies  Eg/ Vegetable, fruit skins, whole grains  Functions – i) burned for energy ii) ribose and deoxyribose sugars (DNA, RNA) iii) structure and strength of plants iv) linked to proteins and lipids  Glycoproteins – covalent link between protein and a carbohydrate monomer; found on cell surfaces; cell-cell adhesion  Glycolipid – forms myelin around neuron axon  Forms of carbohydrates o Monosaccharide – simple form of CHO; 3-9 carbons; glucose, fructose, galactose (C6H12O 6  Sugar Alcohols – used as sweetener; eg/ sorbitol, chemical modification of glucose, body perceives it as sweet (fructose is sweet, glucose is not)  Monosaccharide’s enter CV system through intestinal villi (into capillaries)  travel to liver through hepatic portal vein  galactose and fructose converted to glucose in liver o Disaccharide – sucrose, lactose, maltose o Oligosaccharide – 3-9
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