SMBM 102 Biochemistry Quiz

Biochemistry

• Proteins are long polymers of amino acids and constitute the largest fraction (besides water) of a cell.
• The sum of all the proteins functioning in a given cell is the cell's proteome, and proteomics is the systematic characterization of this protein complement under a specific set of conditions.

Functions of Proteins

• Catalysts - enzymes for metabolic pathways
• Storage and transport - e.g. myoglobin and hemoglobin
• Structural - e.g. actin, myosin
• Coordinated motion – e.g. muscle contraction
• Decoding information - translation and gene expression
• Hormones and hormone receptors
• Immune protection - e.g. antibodies
• Mechanical support – e.g. collagen
• Energy reserve

Amino Acids

• Called α-amino acids because they all have an amino (-NH2) group and a carboxyl group (-COOH) attached to C-2 carbon (α-carbon)
• α-carbon is chiral or asymmetric (4 different groups attached to the carbon; exception - Gly)
• Amino acids exist as stereoisomers (same molecular formula, but differ in arrangement of groups)
• Designated -D or -L; Amino acids in mammalian proteins: L configuration

Classification of Amino Acids

• Based on properties of their R groups
• 1. Amino acids with non-polar (hydrophobic) side chains
• 2. Amino acids with polar (uncharged) side chains
• 3. Amino acids with polar charged side chains

Ionization of Amino Acids

• α-COOH and α-NH2 groups in amino acids are capable of ionizing (as are the R-groups of amino acids)
• Amino acids: weak acids
• At a given pH, amino acids have different net charges
• Can use titration curves for amino acids to show ionizable groups
• Amino acids: amphoteric
• At pH of 7, amino group is protonated (-NH3+) and carboxyl group is ionized (COO-). The amino acid in this form is called a zwitterion

Titration of Amino Acids

• At any given pH one should able to predict the structure of amino acid
• Able to estimate the predominant species
• Ionizable groups on amino acids carry protons at low pH (protonization). At high pH the ionizable groups on amino acids dissociate, releasing protons (deprotonization)

Protein Structure

• Primary structure: linear sequence of amino acids
• Secondary structure: describes protein folding stabilized by H- bonding
• Features: α-helix and β-sheet
• Tertiary structure: overall shape of the protein molecule (folding of a polypeptide into a closely packed three-dimensional structure)
• Quaternary structure: refers to the organization and arrangement of subunits in a protein

Protein Function-Structure Relationships

• Structure, changes in structure are crucial to the function of proteins
• Oxygen transport proteins: understanding their structure and structural changes they undergo is useful in understanding how they function
• Myoglobin (Mb) and Hemoglobin (Hb) are heme proteins that transport oxygen

Myoglobin (Mb)

• Monomeric heme protein found mainly in muscle tissue
• Function: storage and transport of oxygen
• Structure: compact, folded polypeptide chain (153 residues); 75% of Mb: α-helical (8 helices; A,..H)
• Interior: almost entirely nonpolar residues (the only polar amino acids in the interior are two Histidines, which are part of the O2 binding site)
• Contains heme; function of heme: facilitates binding of oxygen to Mb (Mb apoprotein will not bind oxygen)

Hemoglobin (Hb)

• Tetrameric heme protein
• Found in RBCs
• Binds O2 in the lungs and transport to tissues
• Transports CO2 from tissues to lungs
• Each subunit/polypeptide chain of Hb tetramer has a heme prosthetic group and O2 binding site
• Hb: allosteric protein
• Subunits: α- or -β; Hb: (α(2): β(2); α-chain (141), β-chain (146)

Hemoglobinopathies

• Genetic diseases in which the globin subunits of Hb are mutated
• Major hemoglobinopathies include:
  • Sickle cell anemia
  • Hemoglobin C
  • Thalassemias