Which protein remains negatively charged even in acidic pH?

• A. a1-Acid Glycoprotein
• B. Albumin
• C. Transferrin
• D. a1-Antitrypsin

Answer: (A)

The key idea is how a protein’s net charge changes with pH and what gives it a strong, persistent negative charge. A protein’s charge comes from ionizable groups: carboxyl groups tend to be negative, amino groups positive, and the balance between them shifts as pH changes. Some proteins stay negatively charged across a wide pH range primarily because they carry a high density of negatively charged groups that are less easily neutralized when pH drops.

a1-acid glycoprotein is known for being heavily glycosylated with sialic acid residues. These sialic acids contribute many fixed negative charges that endure even as the surrounding pH becomes acidic. The dense negative charge from these sialic acid units dominates the protein’s overall charge, making it remain negatively charged in acidic conditions. The other proteins listed lack this level of constant negative charge from glycan sialylation, so their net charge becomes less negative or even positive as pH lowers toward their isoelectric points.

So the persistent negative charge in acidic pH comes from the abundant negatively charged sialic acid components of a1-acid glycoprotein, setting it apart from the others.