protamine

Protamine is a family of small, highly basic nuclear proteins found in the sperm of many animals, including humans. In mammals the principal protamines are protamine-1 (P1) and protamine-2 (P2). They are extremely arginine-rich and replace histones during spermiogenesis, allowing tight packaging of DNA in the sperm nucleus. The protamines form disulfide cross-links that help stabilize the highly condensed chromatin and protect DNA during transit. Protines are synthesized as precursors in round spermatids and processed to mature forms.

In human reproduction, the proper balance and integrity of protamine content, particularly the P1:P2 ratio, are associated with normal sperm chromatin condensation. Alterations or mutations in the genes PRM1 or PRM2 have been linked to male infertility in some studies, reflecting the importance of protamine-mediated chromatin packaging for fertility.

Protamine sulfate is also used clinically to reverse the anticoagulant effects of unfractionated heparin. It is typically derived from fish milt, commonly salmon. The mechanism involves protamine binding to heparin to form a stable protamine-heparin complex, thereby neutralizing anticoagulation. Dosing depends on the amount of heparin given and the time elapsed since administration, and is administered by slow intravenous infusion to minimize adverse effects.

Adverse effects can include hypersensitivity reactions, hypotension, flushing, arrhythmias, and, in rare cases, anaphylaxis. Individuals with fish allergies or a history of protamine sensitivity are at higher risk.