MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Overview: Amino Acids & Proteins Amino Acids Building blocks of proteins Chemical properties determine biological activity Origin ◦ Majority made in the human Generated from amino acid pool Generated from breakdown of proteins ◦ Essential Amino acids Ingested in diet “MILL PATH TV” Amino Acids Linked together by peptide bonds to form the building blocks of proteins Peptide bond Aminoacidopathies Rare inherited disorders • Enzyme defect that inhibits the body’s ability to metabolize certain amino acids • Abnormality due to problem with enzyme activity or the membrane transport system for amino acids • Cause severe medical problems due to the buildup of toxic amino acids and/or byproducts of amino acid metabolism in blood • Aminoacidopathies: Disorders – Phenylketonuria • Absence of phenylalanine hydrolase • Mousy odor of the urine • Causes significant brain damage – Tyrosinemia • Three types • Type I most severe • Causes liver and kidney damage, affects CNS – Alkaptonuria • Absence of homogentisate oxidase • Urine turns brownish-black upon exposure to air Aminoacidopathies: Disorders – – Maple syrup urine disease • Absence or reduction of alpha-ketoacid decarboxylase • Hallmark feature is the odor of maple syrup or burnt sugar in the urine, breath and skin Isovaleric Acidemia • Absence of isovaleryl-CoA dehydrogenase • Distinctive odor of sweaty feet due to build up of isovaleric acid Aminoacidopathies: Disorders – Homocystinuria • Absence of cystathionine-beta-synthetase – Cystinuria • Defect in amino acid transport system • Results in the formation of stones Proteins • Built from one or more chains of amino acids • Specific • Contain carbon, hydrogen, oxygen, sulfur and nitrogen • Nucleotide sequence in the genes dictates the amino acid sequence of the protein Proteins Synthesis ◦ Plasma proteins made in liver then secreted by hepatocyte into circulation ◦ Immunoglobulins made in plasma cells ◦ Insufficient dietary quantities of amino acids will limit synthesis and lower body levels of proteins Proteins Catabolism (Breakdown) ◦ Goal is to remove nitrogen from the system ◦ Occurs in the digestive tract, kidneys, and liver ◦ Produces ammonia, then urea Urea excreted via urine ◦ Produces ketoacids Ketoacids converted to glucose or fat Structure of Proteins Denaturation Disruption of structure Results in loss of function and protein chemical properties Caused by: ◦ ◦ ◦ ◦ ◦ Heat pH changes Mechanical forces Exposure to UV light Exposure to chemicals Classification of Proteins Simple proteins ◦ Proteins made of only amino acids ◦ Further classified as globular or fibrous Conjugated proteins ◦ Proteins with nonprotein groups attached ◦ Metalloproteins ◦ Lipoproteins ◦ Glycoproteins ◦ Mucoproteins ◦ Nucleoproteins ◦ Phosphoproteins Functions of Proteins Protein Function Examples Enzymes Catalyse chemical reactions Transminases, phosphatases, dehydrogenases Hormones Chemical messengers that control the actions of specific cells or organs Insulin, growth hormone, cortisol Transport Proteins Transport ions, small molecules or macromolecules across biological membranes Hemoglobin, albumin, transferrin Immunoglobulins Mediate humoral immune response to id and neutralize foreign objects IgG, IgM, IgA Structural Structures of cells and tissues Collagen, elastin, keratin Functions of Proteins Protein Function Examples Storage Serve as reserves of metal ions and amino acids ferritin Energy Reserve source of energy Osmotic Force Maintain water distribution between cells and tissue, interstitial compartments and the vasculature albumin References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. http://www.stanford.edu/group/pandegroup/folding/educ ation/prstruc.html Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .