Protamine and Protamine Reactions

First discovered in 1868, protamine is a polycationic, alkaline protein molecule, made up of two-thirds arginine residues and one-third other amino acids. Heads of the sperm of the salmonidae or clupeidae family as well as man are rich in protamine, and salmon milt is the commercial source of protamine. Clinical uses of protamine include the neutralization of heparin used during cardiac or vascular surgery, cardiac catheterization, dialysis and phoresis, and the retardation of insulin absorption in intermediateand long-acting insulin preparations. Because protamine is positively charged, it forms a stable complex with the negatively charged heparin, a heterogeneous compound with alternating residues of iduronic acid and glucosamine; iduronic acid contains 2 sulfate groups and is one of the strongest naturally occurring acids. The protamine–heparin complex is devoid of anticoagulant activities. Protamine-containing insulin preparations are neutral protamine Hagedorn (NPH) insulin and protamine zinc insulin (PZI). Each unit of NPH insulin contains 3 to 6 μg of protamine, and each unit of PZI has 10 to 15 μg of protamine.