99. Proteins can act as excellent buffers because of:
(1) The wide range of pKa values of side chains found within the proteins.
(2) The ability of the terminal regions of the protein to accept or donate H+ ions.
(3) Their hydrogen-bonding capabilities in forming secondary & tertiary structures.
(4) The ease with which H+ &OHions can be absorbed once the protein is hydrolyzed.

Introduction: Buffering and pH Balance in Biology

Maintaining a stable pH is critical for the survival and function of all living organisms. Biological systems rely heavily on buffers—substances that resist drastic changes in pH upon the addition of acids or bases. Among various natural buffers, proteins stand out due to their structural and chemical complexity. But what exactly makes proteins such effective buffers?

Why Proteins Make Excellent Buffers

The buffering capacity of any molecule depends on its ability to accept or donate protons (H⁺ ions). Proteins are particularly well-suited for this function due to the variety of ionizable side chains in their amino acid composition.

✅ 1. Wide Range of pKa Values of Amino Acid Side Chains (Correct Answer)

Each amino acid in a protein can have ionizable side chains with different pKa values—the pH at which the group can gain or lose a proton. Because proteins are made up of 20 different amino acids, many with distinct side chains (like histidine, lysine, glutamate, aspartate, tyrosine, etc.), they collectively span a broad pH range, making them capable of buffering over a wide variety of physiological conditions.

• Histidine, for example, has a pKa near physiological pH (~6.0), making it particularly important in intracellular buffering.

• Glutamate and Aspartate (acidic residues) donate protons at lower pH, while Lysine and Arginine (basic residues) accept protons at higher pH.

Because proteins contain multiple amino acids with overlapping pKa ranges, they can act as multi-site buffers, absorbing or releasing H⁺ ions as needed to resist pH changes.

❌ Other Options Explained

(2) The ability of the terminal regions of the protein to accept or donate H⁺ ions

While the amino (N-terminal) and carboxyl (C-terminal) ends of a protein can indeed participate in acid-base chemistry, their contribution is minimal compared to the side chains within the protein’s interior. Thus, this is not the primary reason proteins act as excellent buffers.

(3) Hydrogen-bonding capabilities in forming secondary & tertiary structures

Hydrogen bonds are critical for maintaining protein structure, but they do not contribute directly to buffering capacity. Buffering depends on acid-base reactions, not structural interactions like hydrogen bonding.

(4) The ease with which H⁺ & OH⁻ ions can be absorbed once the protein is hydrolyzed

This option refers to protein degradation, which is irrelevant to buffering in intact proteins. Buffering occurs without protein hydrolysis and involves reversible protonation/deprotonation of functional groups.

Conclusion: Proteins as Nature’s pH Regulators

Proteins are nature’s versatile buffers, capable of maintaining pH in biological systems across varying conditions. Their diverse range of ionizable side chains with distinct pKa values is the key reason they can neutralize both acids and bases effectively.

This property makes proteins indispensable in intracellular pH regulation, enzyme activity, and homeostasis, ensuring biological systems function smoothly.