Protein metabolism

Two amino acids joined together form a dipeptide Proteins are linear polymers of amino acids • Carboxyl group of one amino acid is linked to the amine group of another amino acid • Linkage is an amide bond or peptide bond • This reaction is a dehydration/condensation reaction as water is released

Proteins cannot function properly unless they fold into their proper shape When a protein loses it proper shape, it said to be denatured • Exposure of proteins to certain chemicals, a change in pH, or high temperature can disrupt protein structure Proteins have four levels of structure: • Primary • Secondary • Tertiary • Quaternary

Primary structure • Primary structure is the linear sequence of amino acids joined together by peptide bonds • Hundreds of thousands of different polypeptides can be built from just 20 amino acids • Changing the sequence of amino acids can produce different proteins

Secondary Structure • Secondary structure is characterized by the presence of alpha helices and beta (pleated) sheets held in place with hydrogen bonds

Tertiary structure • Tertiary structure is the overall three- dimensional shape of a polypeptide • It is stabilized by the presence of: • Hydrophobic interactions • Hydrogen bonding • Ionic salt bridges • Disulfide bridges

Interactions in Tertiary structures • Disulfide bridges between two cysteine side chains • Ionic salt bridges between ionic R groups containing −COO− and − NH3+ • Hydrogen bonds between polar R groups • Hydrophobic interactions between nonpolar R groups that are trying to get away from water molecules

Quaternary structure • Quaternary structure consists of more than one polypeptide • Quaternary structure is maintained by the same forces found in tertiary structure • Sometimes other atoms or molecules are a part of the protein – prosthetic group • Glycoproteins have sugar groups attached • Hemoglobin has iron groups

Chaperone proteins help proteins fold into their normal shapes and correct misfolding of new proteins • Defects in chaperone proteins may play a role in several human diseases, such as Alzheimer disease and cystic fibrosis Prions are misfolded proteins and may cause other proteins to fold incorrectly • May be the cause of a group of fatal brain diseases known as TSEs • Mad cow disease and ALS are examples of TSEs caused by misfolded proteins

Quaternary shape and functions • Fibrous proteins: • Mechanical strength • Structural components • Movement • Globular proteins: • Transport • Regulatory • Enzymes

Heme group is an essential component of the proteins hemoglobin and myoglobin • Fe2+ ion in the heme group is the oxygen binding site • Each hemoglobin contains a heme group which can hold 1 molecule of oxygen

Hemoglobin vs. Myoglobin • Hemoglobin is the oxygen-transport protein of higher animals • Myoglobin is the oxygen storage protein of skeletal muscle Oxygen is transferred from hemoglobin to myoglobin because myoglobin has a stronger attraction for oxygen than hemoglobin does

Hemoglobin Variations • A fetus has a unique type of hemoglobin with slightly greater affinity for oxygen than typical hemoglobin • Another variant is the sickle cell hemoglobin • Valine replaces glutamic acid creating a new hydrophobic region • Hydrophobic regions causes hemoglobin molecules to group together If the gene is inherited from both parents, it causes sickle cell anemia and red blood cells to appear altered

Denaturation • Is the loss of organized structure at the secondary, tertiary and quaternary level • Does not alter primary structure • Cannot be reversed Causes • Change in pH • Heat • Some chemicals

Changes in pH • When an acid or base is added to a protein, it change the charge of the R groups in the protein • This interferes with the salt bridges and hydrogen bonds that stabilize the tertiary structure

Increase in temperature • Causes an increase in the rate of molecular movement of the individual molecules within the solution • As temperature continues to increase, the bonds within the proteins vibrate more violently breaking hydrogen bonds and hydrophobic interactions • The three-dimensional structure of the protein is interrupted • Coagulation occurs when unfolded protein molecules become entangled

Some chemicals and solvents can also interfere with the tertiary and secondary structure of proteins • Organic solvents • Detergents • Heavy metals (Hg2+ and Pb2+) Mechanical stress can also interfere with the 3D structure

When the body has depleted glycogen (starving), it can use amino acids for fuel Degradation takes place in the liver in two stages

1. Removal of the α-amino group    • Typically excreted in the urine    • Transamination

Degradation of the carbon skeleton leads to conversion into a variety of compounds • Pyruvate • Acetyl CoA

Transamination Transaminase catalyzes transfer of α-amino group from α-amino acid to α-keto acid (coenzyme is pyridoxal phosphate from Vitamin B6) • The α-keto acid is often α-ketoglutarate • Transaminase binds the amino acid in its active site • Transfer amino group to pyridoxal phosphate • Next move the amino group to a keto acid

Example: Aspartate Transaminase • This particular transaminase catalyzes the transfer of the α-amino acid of aspartate to α-ketoglutarate • Produces oxaloacetate and glutamate

Example: Alanine Transaminase • This transaminase catalyzes transfer of the α-amino group of alanine to α-ketoglutarate • Produces pyruvate and glutamate • Produce a citric acid cycle intermediate • Provide a direct link between amino acid degradation and the citric acid cycle

Deamination: Removal of the α-amino group • Ammonium ion is removed from the glutamate (that was formed by the transaminase) • Glutamate breakdown is catalyzed by glutamate dehydrogenase

Removal of Ammonium: Urea Cycle • Deamination produces large amounts of ammonium ion • As ammonium ion is toxic it must be removed quickly from the body regardless of the energy required • Eliminate ammonium ion via the urea cycle. Urea is excreted in the urine • Failure of enzymes in the urea cycle can be genetic and leads to hyperammonemia • Severe cases lead to early death from toxic ammonium ion build-up, mental delays, convulsions, and vomiting

The citric acid cycle functions as: • Catabolism = breakdown and harvest • Anabolism = biosynthesis • Amphibolic pathway = both catabolism and anabolism

As amino acids can be converted to citric acid cycle intermediates, these can be used to make amino acids • Oxaloacetate is used to make aspartate in aspartate transamination • Asparagine is made from aspartate in an amination reaction • Glutamate is made from α- ketoglutarate • Glutamine, proline, and arginine are made from glutamate