Biochemistry of Amino Acids and Diseases

Mobility Patterns and Diseases

• Variations in amino acid mobility patterns can indicate certain diseases.

Amino Acid Charge at Neutral pH

• At physiological pH, amino acids possess a negatively charged carboxyl group (–COO–) and a positively charged amino group (–NH3+).
• Amino acids such as glutamate, aspartate, histidine, arginine, and lysine contain additional charged groups in their side chains.
• Amino acids function as ampholytes, acting as both acids and bases.

Henderson-Hasselbalch Equation

• Used to predict pH changes based on concentrations of bicarbonate (HCO3–) and carbon dioxide (CO2).
• Calculates how pH responds to changes in concentrations of weak acids and their salt forms.
• In the bicarbonate buffer system, it illustrates the influence of HCO3– and CO2 on pH.

Drugs and Ionizable Forms

• Many drugs are weak acids or bases; their absorption depends on their charged or uncharged forms.
• Acidic drugs release protons and become negatively charged, while basic drugs lose protons and become uncharged.
• Uncharged forms of drugs permeate membranes more readily, influencing their effective concentration at absorption sites.

Cross-Links in Concept Maps

• Concept maps can include cross-links to represent complex ideas across different topics.
• Facilitates understanding of relationships in biochemistry and enhances preparation for exams like the USMLE.

Amino Acid Structure

• Each amino acid has an α-carboxyl group and a primary amino group, except proline, which has a secondary amino group.
• Physiological pH leads to dissociation of the α-carboxyl group and protonation of the α-amino group.
• Amino acids possess distinct side chains (R groups) that classify them as nonpolar, uncharged polar, acidic (polar negative), or basic (polar positive).

Buffer Systems

• Free amino acids and charged amino acids in peptide chains function as buffers.
• Buffering effectiveness is highest within ±1 pH unit of the pKa, where [A–] = [HA].

Chiral Carbon

• The α-carbon of amino acids (excluding glycine) is a chiral carbon connected to four different groups, exhibiting optical activity.
• L-forms of amino acids are incorporated into proteins in humans.

Secondary Structure of Proteins

• β-sheets can form from multiple polypeptide chains arranged parallel or antiparallel, with interchain or intrachain bonds.
• α-helices and β-sheets maximize hydrogen bonding among peptide bond components.

β-Bends and Nonrepetitive Structures

• β-Bends consist of four amino acids and help reverse polypeptide chain direction for compact shapes.
• Nonrepetitive secondary structures occupy roughly half of globular proteins, possessing less regular organization than repetitive structures.

Oxygen-Dissociation Curve

• The sigmoidal shape of the oxygen-dissociation curve in hemoglobin enables efficient oxygen transport between high and low pO2 areas.
• Myoglobin has a hyperbolic curve, which limits oxygen release efficiency.

Bohr Effect

• Oxygen release from hemoglobin increases with lower pH or higher pCO2, stabilizing the deoxygenated T state and shifting the curve to the right.
• Higher pH and lower CO2 concentration shift the curve left and stabilize the oxygenated R state.

Carbonic Acid and Bicarbonate

• Increased CO2 in active tissues leads to a lower pH as it forms carbonic acid, contributing to the unloading of oxygen from hemoglobin.
• This pH gradient favors oxygen release in tissues and uptake in lungs.

CO2 Transport and Carbaminohemoglobin

• CO2 is mainly transported as bicarbonate but also binds to hemoglobin to form carbaminohemoglobin, stabilizing the deoxygenated form and decreasing oxygen affinity.

Carbon Monoxide Binding

• CO binds tightly to hemoglobin, shifting the oxygen-dissociation curve left and impairing oxygen release due to high affinity for heme.
• CO poisoning requires treatment with high-pressure oxygen to displace CO from hemoglobin, preventing cellular damage and hypoxia.

Additional Gas Transport

• Hemoglobin also transports nitric oxide (NO), which acts as a vasodilator, contributing to its functions in the body.