BIOCHEMISTRY

I apologize for the following: 1. 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

Our targets:
1.Explain life processes in the molecular level 2.Success in tests and exams 3.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

Useful References:
1. Lippincotts Biochemistry, 3rd edition 2. Marks Basic Medical Biochemistry, 2nd ed

Scope of Biochemistry
Structure

BIOMOLECULES
Function

BIOCHEMISTRY Anabolism

METABOLIC PATHWAYS
Catabolism

Lord of the Fuel

Fellowship of the Caribs

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

Scope of Biochemistry
feed/fast insulin/glucagon obesity nutrition vitamins

INTEGRATION OF METABOLISM
BIOCHEMISTRY

Central Dogma

Replication Transcription Translation

Biotechnology

THE

SUM OF ALL GENES

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

CHEMICAL AND BIOLOGICAL FOUNDATIONS OF BIOCHEMISTRY

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

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

Simple Molecules are the Units for Building Complex Structures

Metabolites and Macromolecules Organelles Membranes The Unit of Life is the Cell

Replication

Transcription

Translation

DIET

phenotype

PROTEINS NORMAL FUNCTION

ENV

family

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

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

pKa = 2.0

Free amino acids are zwitterionic at physiological pH.

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

hydrophobic

hydrophilic

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

Why know the nature of the R groups?

The R group of an amino acid dictates its properties and reactivity.

The Henderson- Hasselbalch Equation

Buffers are solutions which resist change in pH following the addition of an acid or base

REVIEW OF UNDERGRADUATE CHEMISTRY:

Amino acids are weak acids The acid dissociation constant is given by:
1. HA H+ + A-

2. pX = -log[X]

Ka =

[ H +] [A-]

[HA]
The larger the Ka, the stronger the acid.

3. pH < pKa protonated pH > pKa deprotonated

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. 3.9 B. 4.9 C. 5.9 D. 6.9 E. 7.9

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 1 B. 100 to 1 C. 1000 to 1 D. 1 to 100 E. 1 to 1000

TEST Yourself!
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

APPLICATIONS OF THE HENDERSONHASSELBALCH EQUATION

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

pI = pK1 + pK2 2