bioco intro
DESCRIPTION
Biochemistry UPR RCMTRANSCRIPT
Fundamentals of Molecular Biology (BIOCHEMISTRY)MPRI7119
Jeylin Rodríguez Fernández – [email protected] Frances Marrero Barrera – [email protected]
Objectives•Course Structure•Know your faculty•Learn techniques and materials for high
yield study•An overview of everything (3 Blocks)
▫Tests▫Professors▫Material
Course Structure•Evaluation
▫3 tests (75%)▫Team Based Learning (TBL)▫Small Group Activities (SGA)▫Flipped Classroom (FCR)
Quiz▫Clinical Correlations (CC)▫Humanistic Activity▫Attendance (2%)▫SHELF (15%)
(8%)
Grading
•A 100 – 87.45•B 87.44 – 78.45•C 78.44 – 69.45•Repo 69.44 – 60
F Everything else
Reasonable Accomodation• Students with health conditions or situation that
according to the law makes them eligible for reasonable accommodation have the right to submit a written application to the Dean, Associated Dean or Assistant Dean for student affairs of their faculty.
• Additional time: Half the duration of the test.
• http://www.rcm.upr.edu/portalstu/documentos.aspx
SHELF
•Some Humorous Exam Lacking Focus•15%•Less than 24 hrs to study!•Suggestion: SLEEP or BRS
Comprehensive Exam
Know Your Faculty• Pardo “FOREVER & EVER” means forever & ever !
HIGHLIGHT what she emphasizes and different colored words are important.
• Baerga Really good class. PPTs lack text. (2,3 BPG learn it in different situations)
• Banerjee Lippincott’s FULL. Do Devlin questions for practice.
• Cadilla PPTs are very very VERY dense, lots of text. Go to class. Outside material is unnecessary, ppts have enough info and more. (Molecular Diagnostics very important)
Know Your Faculty• Su doable questions
• Sixto (aka Santa) If you ask he tells you what’s important for the test. Go to class. Anything he doesn’t mention, isn’t coming. Easy questions.
• Jimenez P450 & metabolic interrelationship. He really enjoys giving class. You might get something out of going.
• Preston You can study all you want, you still won’t understand his questions.
• Orengo go to class, questions are about things he says that aren’t necessarily on the ppts.
What to use?• Devlin (VS) waaaaaay
too dense. NO TIME.
• Mark’s (VS) Some found it useful
• PPTs MUST READ!
• Lippincott’s The MESSIAH▫ Gives you the general
story and then the “cucarachas” you fill in with the ppts
What to do?
•Questions▫Practice, practice, practice▫BRS▫Lippincott’s▫Lippincott’s Q & A▫Q bank (This will be provided in 2nd year
for your STEP 1 prep, if you wish you can purchase it before)
Overview
•3 exams•1 month, 1 week•SGAs•FCRs (+ Quizzes)•CCs
Block 1• First test (90 + 6 self study + 4 bonus = 100 Qs)
▫Water▫Acid-Base▫Cell biology (Cell cycle, proteins)▫Genetics PARDO!▫Protein synthesis, translational and post-
translational modification▫Molecular Diagnostics▫CC: Chromosomal disorders, Alpha-1
antitrypsin deficiency
Block 1• First test (90 + 6 self study + 4 bonus = 100 Qs)
▫Water▫Acid-Base▫Cell biology (Cell cycle, proteins)▫Genetics▫Protein synthesis, translational and post-
translational modification▫Molecular Diagnostics▫CC: Chromosomal disorders, Alpha-1
antitrypsin deficiency
Cell Biology Review• Cell Cycle and Mitosis
▫ https://www.youtube.com/watch?v=JcZQkmooyPk
• Meiosis▫ https://www.youtube.com/watch?v=rqPMp0U0HOA
• Comparison of these two▫ https://www.youtube.com/watch?v=OGX8Bn7Kjjc
• DNA Replication▫ https://www.youtube.com/watch?v=27TxKoFU2Nw
Cell Biology Review•Transcription and Translation:
▫https://www.youtube.com/watch?v=5MfSYnItYvg
▫https://www.youtube.com/watch?v=8dsTvBaUMvw
▫https://www.youtube.com/watch?v=6YqPLgNjR4Q
Block 2• Second Exam (88 New + 8 old + 4 bonus = 100 Qs)
▫ Enzyme Kinetics & Thermodynamics Baerga▫ Enzyme Regulation Baerga▫ Signal Transduction ▫ Carbohydrate Metabolism (I-IV) Banerjee
Glycolysis and its regulation + TCA Cycle Glycogen metabolism Pentose Phosphate Pathway (PPP) Gluconeogenesis + Glycoconjugates & Glycobiology
▫ Bioenergetics and Oxidative Metabolism▫ Lipids and Lipids Metabolism▫ CC: Glucose 6-phosphate dehydrogenase deficiency and acute
hemolytic anemia, Wernicke-Korsakoff Syndrome, Hypoglycemia and Premature Infants, Hypoglycemia and Alcohol Intoxication, Galactosemia
Block 2• Second Exam (88 New + 8 old + 4 bonus = 100 Qs)
▫Enzyme Kinetics & Thermodynamics ▫Enzyme Regulation▫ Signal Transduction
▫Carbohydrate Metabolism (I-IV) Glycolysis and its regulation + TCA Cycle Glycogen metabolism Pentose Phosphate Pathway (PPP) Gluconeogenesis + Glycoconjugates & Glycobiology
▫ Bioenergetics and Oxidative Metabolism▫ Lipids and Lipids Metabolism▫ CC: Glucose 6-phosphate dehydrogenase deficiency and acute
hemolytic anemia, Wernicke-Korsakoff Syndrome, Hypoglycemia and Premature Infants, Hypoglycemia and Alcohol Intoxication, Galactosemia
Enzyme Kinetics & Thermodynamics
• Graphs are super important
• Kinetics vs. Thermodynamics▫ Thermodynamics – Total
energy involved in a reaction ΔG (energy)
▫ Kinetics – How quickly does a reaction reach equilibrium k (rate constant) ENZYMES
A reaction is at equilibrium when:
•A) theΔGº’ is negative•B) the ΔG is negative•C) the ΔGº’ is positive•D) the ΔG is positive•E) the ΔG is zero
A reaction is at equilibrium when:
•A) theΔGº’ is negative•B) the ΔG is negative•C) the ΔGº’ is positive•D) the ΔG is positive•E) the ΔG is zero
The Gibbs free energy (ΔG) is negative for:
•A) exergonic process•B) endergonic process•C) nonspontaneous process•D) temperature-independent processes
•E) concentration of reactants and products <1.0 M
The Gibbs free energy (ΔG) is negative for:
•A) exergonic process•B) endergonic process•C) nonspontaneous process•D) temperature-independent processes
•E) concentration of reactants and products <1.0 M
Enzyme Kinetics: Michaelis-MentenVelocity (v) vs substrate concentration ([S])
Lineweaver-Burk Plot
Small details• Km: [substrate] at v = ½ Vmax
▫ Describes the affinity of the substrate for the enzyme.▫ Kinetics
• Keq: Equilibrium constant▫ Thermodynamics
• CAREFUL NOT TO MIX THERMODYNAMICS WITH KINETICS. An enzyme does NOT affect the equilibrium constant of a reaction, only the speed at which it reaches equilibrium.
• Lineweaver-Burk Plot IMPORTANT▫ x-intercept: -1/Km
▫ Slope: Km/Vmax
▫ y-intercept: 1/Vmax
Enzyme Regulation
Enzyme Regulation
Why is any of this relevant?•Regulation of pathways
•Metabolism
•Industrial applications
•Pretty much everything
•DRUGS
Clinical Correlates• Physostigmine: a competitive reversible inhibitor of
acetylcholinesterase (AChE)▫myasthenia gravis
• Angiotensin-converting enzyme (ACE) inhibitors: inhibit formation of angiotensin II from angiotensin II▫antihypertensive therapies
• Nerve gases: irreversible inhibitors of AChE; a ‘‘suicide’’ inhibitor▫ALLOPURINOL is a suicide inhibitor used to treat
gout.
Signal Transduction• Major types of membrane receptors
▫ Ion channel receptors▫Tyrosine kinase receptors▫Serine-threonine kinase receptors▫G Protein-Coupled Receptors (GPCR)▫Guanylyl cyclase receptors
• Important to know the receptor, its conformation, pathway, substrate, secondary messengers, distal activity, and associated pathologies▫E.g. GPCR, membrane-bound heptahelical receptor,
via PKA, somatostatin, cAMP, inhibition of GH, acromegaly Tx
Carbohydrate metabolism
What to focus on• Rate limiting steps
• Irreversible steps
• Co-factors
• Regulation▫ Activators▫ Inhibitors
• Integration
Secret to success?KEEP CALM, TAKE IT STEP BY STEP. WRITE EACH
PATHWAY FORWARD AND BACKWARD EVERYDAY UNTIL IT STICKS.
Glycolysis& Gluconeogenesis
Glycolysis& Gluconeogenesis
Cucaracha material that you should probably know:BPG is dephosphorylated to form Pi and 3-phosphoglycerate.
Regulation of Glycolysis
Pyruvate Dehydrogenase Complex (PDC)
TPP
Citric Acid Cycle (aka Kreb’s Cycle)
Citric Acid Cycle (aka Kreb’s Cycle)
Positive/negative Feedback
Electron Transport Chain (ETC)
COKCN
Interference with Oxidative Phosphorylation (Uncoupling)
Uncouplers DNP FCCP
Brown fat(thermogenin)
UCPs
Products of metabolism
Glycogen metabolism
Cori
McArdle
Glycogen storage diseases (GSDs)•Very high yield•Very Poor Carbohydrate Metabolism
▫Von Gierke disease (type I)▫Pompe disease(type II) - movie on this one▫Cori disease (type III)▫McArdle disease (type V)
McArdle = Muscle Coca-Cola Urine
•Lysosomal Storage Disorders (LSDs) and Mucopolysaccharidoses (MSPs) are also very high yield
POP QUIZ!A 30-year-old woman is enduring her first trimester of pregnancy. As the mother’s hemoglobin relinquishes oxygen to the greater affinity fetal hemoglobin, it changes back to the relaxed form. This process also releases the allosteric factor 2,3-bisphosphoglycerate (BPG). If the allosteric factor then enters glycolysis, how much energy will it net by the end of its oxidative pathway?A) 0 ATPB) 1 ATPC) 2 ATPD) 4 ATPE) 6 ATP
Let’s review
POP QUIZ!A 30-year-old woman is enduring her first trimester of pregnancy. As the mother’s hemoglobin relinquishes oxygen to the greater affinity fetal hemoglobin, it changes back to the relaxed form. This process also releases the allosteric factor 2,3-bisphosphoglycerate (BPG). If the allosteric factor then enters glycolysis, how much energy will it net by the end of its oxidative pathway?A) 0 ATPB) 1 ATPC) 2 ATPD) 4 ATPE) 6 ATP
In an embryo with a complete deficiency of pyruvate kinase, how many net moles of ATP are generated in the conversion of 1 mole of glucose to 1 mole of pyruvate?
A) 0B) 1C) 2D) 3E) 4
Let’s review
In an embryo with a complete deficiency of pyruvate kinase, how many net moles of ATP are generated in the conversion of 1 mole of glucose to 1 mole of pyruvate?
A) 0B) 1C) 2D) 3E) 4
The enzyme pyruvate dehydrogenase (PDH):
A) contains only one polypeptide chainB) requires thiamine pyrophisohate (TPP) as a cofactor.C) produces oxaloacetate from pyruvate.D) is converted to an active form by phosphorylation.E) is activated when NADH levels increase.
The enzyme pyruvate dehydrogenase (PDH):
A) contains only one polypeptide chainB) requires thiamine pyrophisohate (TPP) as a cofactor.C) produces oxaloacetate from pyruvate.D) is converted to an active form by phosphorylation.E) is activated when NADH levels increase.
A 24-year-old student is training for the track and field events at her college. She presents to her physician with complaints of severe muscle cramps and weakness when training. Muscle biopsy demonstrates glycogen accumulation, liver biopsy is unremarkable, and laboratory tests indicate a deficiency of myophosphorylase (muscle glycogen phosphorylase). Which of the following is the most likely diagnosis? (hint: She probably also pees Coca-cola-colored urine)
(A) Andersen disease(B) Cori disease(C) McArdle disease(D) von Gierke disease(E) Hers disease
A 24-year-old student is training for the track and field events at her college. She presents to her physician with complaints of severe muscle cramps and weakness when training. Muscle biopsy demonstrates glycogen accumulation, liver biopsy is unremarkable, and laboratory tests indicate a deficiency of myophosphorylase (muscle glycogen phosphorylase). Which of the following is the most likely diagnosis? (Hint: She probably also pees Coca-cola-colored urine)
(A) Andersen disease(B) Cori disease(C) McArdle disease(D) von Gierke disease(E) Hers disease
Block 3•Third Exam (90 new + 10 old + 4 bonus =
104 Qs)▫ Lipids ▫ Metabolic Interrelationships ▫ Heme and Porphyrin Metabolism Pardo▫ Amino Acid Metabolism Pardo▫ Nucleotides Metabolism▫ Novel Therapies ▫ Vitamins and Minerals Pardo▫ Biochemical Pearls and Neuro Metabolism Pardo▫ CC: Peroxisomal Oxidation Disorders, Blood as a
Diagnostic Tool, Obesity, Diabetes and Metabolic Syndrome, Cancer, Hormones, Coagulopathies.
Block 3• Third Exam (90 new + 10 old + 4 bonus = 104
Qs)▫Lipids▫ Metabolic Interrelationships▫ Heme and Porphyrin Metabolism▫ Amino Acid Metabolism▫ Nucleotides Metabolism▫ Novel Therapies
▫Vitamins and Minerals▫ Biochemical Pearls and Neuro Metabolism▫ CC: Peroxisomal Oxidation Disorders, Blood as a Diagnostic
Tool, Obesity, Diabetes and Metabolic Syndrome, Cancer, Hormones, Coagulopathies.
Lipids Overview •Important Functions:
▫Fuel: Fatty Acids (R-COOH) on breakdown form Acetyl CoA,
NADH and FADH2. When attached to glycerol they can be stores as
triglycerides (fat).
▫Cell Membranes: Sphingomyelin, cerebrosides and gangliosides
Nervous System
▫Steroid Hormones: Cholesterol
▫Bile Acids: They are lipids Emulsify fats
Lipids Overview•Important Functions:
▫Prostaglandins: Derived from polyunsaturated fatty acids
Arachidonic Acid Numerous hormone-like effects Smooth
muscle contraction, platelet aggregation and inflammatory response.
▫Fat-soluble vitamins A, D, E, K They are lipids. VEEEEEERY IMPORTANT!!!!
Fatty Acids
• Unsaturated double bonds.▫Linoleic acid (C18)▫Linolenic acid (C18)▫Arachidonic acid (C20)
• Saturated only single bonds.▫Palmitic acid (C16)
• Number of carbons typically is even, reflecting the fact that the fatty acid chains are built up (and broken down) in units of 2 carbon atoms at a time.
Lipids as a source of energy: Oxidation of Fatty Acids
• Fatty acid breakdown = important source of energy▫ NADH and FADH2 energy molecules
▫ Acetyl CoA is formed Krebs cycle
• Each round of 2 carbon losses produces its own NADH, FADH2 and Acetyl CoA:▫ 17 ATPs for each round of 2-carbon losses!
• Lipids are more energy efficient molecules than carbohydrates.
KEY!!!
•Fatty acid SYNTHESIS occurs in the cytoplasm
•Fatty acid OXIDATION occurs in the mitochondria
β-Oxidation cycle
β-Oxidation cycle
β-Oxidation: Energetic Balance
Fatty Acids as a Source of Energy•When blood sugar is low:
▫Epinephrine ▫Norepinephrine ▫Glucagon
• Insulin:▫Inhibits lipid breakdown▫Promotes the transport of glucose into cells,
especially fat cells, where glucose can then be converted and stored as triglycerides.
Stimulate a lipase in fat cells to break down triglycerides.
Ketones• Produced in the course of breakdown of the fatty acids.
• At some point the breakdown reaches the point where the fatty acid is degraded to the 4-carbon Acetoacetyl CoA that can:▫ Break down further to acetyl CoA▫ Change to ketones:
Acetoacetate (C4) Hydroxybutyrate (C4) Acetone (C3)
▫ Be used for the synthesis of cholesterol and its many derivatives.
• Commonly elevated in blood in states of starvation and in diabetes mellitus:▫ Triglycerides break down to provide fatty acids and acetyl CoA
as fuel, sometimes with the formation of ketones as well.
Vitamins• Vitamins are chemicals that are necessary in trace
amounts for normal body function.
• Must come from external food sources.
• Water-soluble:B1 (thiamine) B2 (riboflavin)B6 (pyridoxine) B12 (cobalamin)C (ascorbic acid) FolateBiotin Niacin
• Fat-soluble:A, D, E, K
Water-Soluble Vitamins• B1:
▫ Common food sources wheat germ and whole grain cereals.
▫ Deficiency: Beri-beri: SOLO COMEN ARROZ!. Cardiac and neurologic
complications, general weakness, pins-and-needles sensations and pain in the legs.
Wernicke-Korsakoff: correlated with alcoholism. Psychosis, CONFABULATION, memory loss.
• B2:▫ Common food sources fish, meat, eggs, milk, green
vegetables.▫ Deficiency:
Angular somatitis (cracks in the corner of the mouth), anemia, inflammation of the tongue.
Water-Soluble Vitamins•B6:
▫Common food sources whole grain cereals, fish, meat, eggs, milk.
▫Deficiency:Dermatitis, glossitis, anemia.
•B12:▫Common food sources Only microorganisms
make it. It is stored in the liver.▫Deficiency:
Pernicious anemia
Water-Soluble Vitamins• Vitamin C:
▫Common food sources fruits and vegetables.▫Deficiency: PIRATES OR PEOPLE ON SHIPS
Scurvy: swollen gums and easy bruisability (defective collagen formation)
• Folate:▫Common food sources cereals, green leafy
vegetables.▫Deficiency:
Pregnancy Neural tube defects. Resembles B12 deficiency so far the anemia goes,
but without the neurologic abnormalities.
Water-Soluble Vitamins
•Niacin:▫Common food sources fish, peanuts,
wheat germ.▫Deficiency:
PELLAGRA: 3 D’s : HARTNUP’s DISEASE Diarrhea, Dermatitis, Dementia
Fat-Soluble Vitamins
•Vitamin A:▫Deficiency:
Night blindness and xerophtalmia (dry cornea-ulceration of the cornea.
•Vitamin D:▫Deficiency: Ca2+ deficiency
Children: Rickets (bending with poor calcification of developing bone.)
Adults: Osteomalacia (decalcification and softening of bones.)
Fat-Soluble Vitamins•Vitamin K:
▫Deficiency: Newborns: hemorrhagic disease of the
newborn.
High Yield Facts• Sickle cell mutation: VALINE GLUTAMATE (Position 6 of the β
subunit.)
• Osteogenesis Imperfecta Brittle bones, baby with multiple fractures…COLLAGEN TYPE 1.▫ Pardo LOOOOOOOVES this!
• Fragile X: most common cause of INHERITED mental retardation.▫ Big Ears▫ And she ADOOOOOOORES this for test questions!
• Down Syndrome: Trisomy 21, single palmar crease. Most common cause of CONGENITAL mental retardation.
• PEDIGREES!!! Know the trends, learn to love them.
High Yield Facts•Collagen Disorders:
▫Col I – Osteogenesis Imperfecta▫Col II and Col III – (two types) : Ehlers-
Danlos (two names)▫Col IV – Alports (NO HAY TRUCO)
•Variable Expressivity:▫Neurofibromatosis (CLASSIC!)
Café au laitTumors
Neurofibromatosis
High Yield Facts• Prader Wili: Father or Paternal copy missing
• AngelMan: Maternal copy missing
• Cri du chat: Cat Cry Deletion of the small limb of chromosome 5.
• Anticipation:▫ Trinucleotide repeats▫ Type of Variable Expressivity▫ Increase with each generation▫ HUNTINGTON’S (CAG)▫ FRAGILE X (CGG)
High Yield Facts•Trisomies:
▫Patau (Puberty) 13▫Edwards (Election) 18▫Down (to Drink) 21
Pop Quiz!
Pop Quiz1. The following products form on fatty acid
breakdown:
A. CO2, Acetyl CoA, NADH
B. Acetyl CoA. NADH, H2O, FADH2
C. NADH, Acetyl CoA, FADH2
D. Electrons and Acetyl CoA
Prueba
1. The following products form on fatty acid breakdown:
A. CO2, Acetyl CoA, NADH
B. Acetyl CoA. NADH, H2O, FADH2
C. NADH, Acetyl CoA, FADH2
D. Electrons and Acetyl CoA
Prueba2. Protaglandins are derived from __________ and one of its hormone-like effects is ______________.
A. Vitamins, smooth muscle contractionB. Arachidonic acid, sweatingC. Arachidonic acid, inflammatory
responseD. Vitamins, inflammatory response
Prueba2. Protaglandins are derived from __________ and one of its hormone-like effects is ______________.A. Vitamins, smooth muscle contractionB. Arachidonic acid, sweatingC. Arachidonic acid, inflammatory response
D. Vitamins, inflammatory response
Prueba3. Lipids are more energy efficient molecules that carbohydrates.a. Trueb. False
Prueba3. Lipids are more energy efficient molecules that carbohydrates.a. Trueb. False
Prueba4. Fatty acid SYNTHESIS occurs in the
___________ and fatty acid oxidation occurs in the _______________.
A. Mitochondria, cytoplasmB. Nucleus, cytoplasmC. Cytoplasm, nucleusD. Cytoplasm, mitochondria
Prueba4. Fatty acid SYNTHESIS occurs in the
___________ and fatty acid OXIDATION occurs in the _______________.
A. Mitochondria, cytoplasmB. Nucleus, cytoplasmC. Cytoplasm, nucleusD.Cytoplasm, mitochondria
Prueba5. The 4 steps of fatty acid oxidation (in order) are:A. Reduction, hydration, thiolysis,
oxidationB. Oxidation, hydration, thiolysis,
reductionC. Hydration, oxidation, thiolysis,
oxidationD. Oxidation, hydration, oxidation,
thiolysis
Prueba5. The 4 steps of fatty acid oxidation (in order) are:A. Reduction, hydration, thiolysis,
oxidationB. Oxidation, hydration, thiolysis,
reductionC. Hydration, oxidation, thiolysis, oxidationD. Oxidation, hydration, oxidation,
thiolysis
Prueba
6. The deficiency of vitamin C causes:A. PellagraB. ScurvyC. DiarrheaD. Beri-beri
Prueba6. The deficiency of vitamin C causes:A. PellagraB.ScurvyC. DiarrheaD. Beri-beri
Take Home Message• BIOCO IS IMPORTANT• You should not ignore it!• It can help you in future classes!• IT’S GONNA BE HARD, BUT YOU CAN DO
IT!• We are here to help you, if you need help,
ASK FOR IT!
•DISFRUTEN SU VERANO!!!!!!!!!!!!!!!!!!!!!!!