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What in the living world isn't biochemistry?

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I apologize for the following: My fast talking speed and accent 2. Some mistakes I am sure I will commit but will try to correct along the way 3. Modifications in the PowerPoint files which may occur on a daily basis 4. My intent is for us all to be dangerous biochemists

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Our targets: Explain life processes in the molecular level Success in tests and exams Prepare for the USMLE Exam Step 1 Policies: 1. Attendance should be 90% of the total class hours. 2. 3 Assessment Tests 3. Final Semester Examination

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Useful References: Lippincott’s Biochemistry, 3rd edition Mark’s Basic Medical Biochemistry, 2nd ed

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Scope of Biochemistry BIOMOLECULES Anabolism Catabolism METABOLIC PATHWAYS BIOCHEMISTRY Structure Function

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This class is ENERGY driven! We will learn how biomolecules are broken down to produce ATPs. Emphasis will also be given on CLINICAL CORRELATIONS.

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Scope of Biochemistry INTEGRATION OF METABOLISM Replication Transcription Translation Biotechnology Central Dogma BIOCHEMISTRY feed/fast insulin/glucagon obesity nutrition vitamins

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Medical Genetics is all about single gene inheritance, cancer genetics, molecular diagnosis and gene therapy.

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FUNCTIONAL GROUPS ON MOLECULES Various structurally diverse compounds Carbohydrates-classified by their carbonyl groups No of carbons etc Lipids-defined by their hydrophobicity. Major are the fatty acids esterified to glycerol to form TAGs

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Fatty acids with carboxyl group Sphingolipids-FA + sphingosine Glycolipids PUFA-precursors of eicosanoids Nitrogen containing compounds e.g. amino acids, purines and pyrimidines. Nitrogen in amino groups or heterocyclic ring structures often carries a positive charge at neutral pH

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Simple Molecules are the Units for Building Complex Structures Metabolites and Macromolecules Organelles Membranes The Unit of Life is the Cell

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Replication Transcription Translation PROTEINS NORMAL FUNCTION DIET ENV phenotype family

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Amino Acids: Building Blocks of Proteins

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- polymer of L-amino acids - functionally diverse molecules e.g. metabolism, transport, cell communication, movement, “scaffolding” - 1°structure is determined by 20 a. a determined by the genetic code. Proteins

Nature of the side chain dictates the function of the amino acid

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Free amino acids are zwitterionic at physiological pH. pKa = ? 2.0

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20 Common Amino Acids found in proteins CLASSIFICATION-based on side chain Non-polar amino acids (hydrophobic) Polar, uncharged amino acids (hydrophilic) Polar, charged amino acids (hydrophilic) -Acidic amino acids -Basic amino acids

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Several Amino Acids Occur Rarely in Proteins Hydroxylysine, hydroxyproline - collagen ?-Carboxyglutamate - blood-clotting proteins Phosphorylated amino acids – a signaling device Hormones – epinephrine Allergic response - histamine

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Why know the nature of the R groups? The R group of an amino acid dictates its properties and reactivity.

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The Henderson- Hasselbalch Equation Buffers are solutions which resist change in pH following the addition of an acid or base

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Amino acids are weak acids The acid dissociation constant is given by: 1. HA ? H+ + A- Ka = [ H + ] [ A - ] [HA] REVIEW OF UNDERGRADUATE CHEMISTRY: 2. pX = -log[X] 3. pH < pKa protonated pH > pKa deprotonated The larger the Ka, the stronger the acid.

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Test Yourself! You have just admitted a male infant with a congenital deficiency for pyruvate dehydrogenase and you suspect lactic acidosis. The laboratory reports that the urine contains 0.01 mM lactic acid and 1.0 mM lactate ions. What is the pH of the urine? (Lactic acid, pK = 3.9) A. 3.9B. 4.9C. 5.9D. 6.9E. 7.9

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Test Yourself! What is the ratio of the conjugate acid to the conjugate base of the side chain of lysine-86 in the brain protein, windsorstudentin, at pH 6.0, if the pK for the group is 9.0? A. 10 to 1B. 100 to 1C. 1000 to 1D. 1 to 100E. 1 to 1000

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Which of the following describes the side chain of valine? A. contains sulfur B. contains a branched chain hydrocarbon C. contains an aromatic ring D. cyclic E. unbranched with primary amine TEST Yourself!

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Acid-Base Balance Respiratory Acidosis – chronic lung disease Respiratory Alkalosis- head injuries or drug-induced toxicity Metabolic Acidosis- increased ketogenesis, diarrhea, kidney failure Metabolic Alkalosis- administration of salts of metabolic acids, vomiting

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pI = pK1 + pK2 2