What hormones and elements, such as ions (e.g. calcium, sodium, potassium) and hormones (e.g. thyroxine, cortisol), does albumin bind with in the body, particularly in patients with a history of hypertension, diabetes, and other cardiovascular risk factors?

Albumin Binding in the Body

Albumin binds calcium, magnesium, sodium, potassium, fatty acids, thyroid hormones (thyroxine), steroid hormones (cortisol), bilirubin, and numerous drugs in the circulation. 1, 2, 3

Major Ions and Elements Bound by Albumin

Divalent Cations

• Calcium: Albumin is the primary binding protein for calcium in serum, with approximately 40-45% of total serum calcium bound to albumin 1
• Magnesium: Albumin binds magnesium ions, though to a lesser extent than calcium, playing a role in maintaining magnesium homeostasis particularly in patients with hypertension and diabetes 4
• Copper and Nickel: Region 4 of the albumin molecule contains a specific high-affinity binding site for metal ions, particularly Cu++ and Ni++ 1

Monovalent Ions

• Sodium and Potassium: Albumin participates in electrolyte balance by binding these ions, which is particularly critical in patients with congestive heart failure, hypertension, and diabetes 4
• Chloride: Region 2 of albumin accommodates chloride ion binding 1

Hormones Bound by Albumin

Thyroid Hormones

• Thyroxine (T4): Albumin binds thyroxine at Region 2, serving as a secondary transport protein for thyroid hormones (after thyroid-binding globulin) 1

Steroid Hormones

• Cortisol: Albumin transports cortisol and other steroid hormones in the circulation, though with lower affinity than cortisol-binding globulin 2

Endogenous Ligands with Clinical Significance

Fatty Acids

• Long-chain fatty acids: Region 1 of albumin is highly specific for binding one or possibly two long-chain fatty acid ions with high affinity 1
• Medium-chain fatty acids: At least seven distinct binding sites exist for fatty acids of varying chain lengths, including Sites I and II 3
• Octanoate: Binds at Region 2 along with other small molecules 1

Bilirubin and Heme

• Bilirubin: Region 3 of albumin accommodates bilirubin binding, which is clinically important for preventing kernicterus in neonates 1
• Haemin: A separate binding region (Region 5) exists specifically for strong binding of heme 1

Structural Considerations for Binding

Binding Site Architecture

• Site I and Site II: These two major drug binding sites are highly conserved among mammals and accommodate diverse ligands based on their physical and chemical properties 3
• Hydrophobic channels: The albumin molecule contains hydrophobic channels formed by helical structures where basic and hydrophobic amino acid residues facilitate ligand binding 1
• Conformational flexibility: Albumin's ability to fluctuate between isomeric forms (N-B transition) allows it to adapt and bind structurally diverse ligands with high affinity 1

Clinical Implications in Cardiovascular Risk Patients

Monitoring Considerations in Hypertension and Diabetes

• Potassium monitoring: When ACE inhibitors, ARBs, or diuretics are used in hypertensive or diabetic patients, serum potassium levels must be monitored for changes, as albumin-bound potassium dynamics can be affected 5
• Calcium and magnesium regulation: Patients with hypertension and diabetes require careful regulation of albumin-bound calcium and magnesium levels to prevent complications 4

Drug Binding Implications

• Multiple drug binding regions: At least 6 distinct regions on albumin bind various drugs, which is particularly relevant in patients with cardiovascular risk factors who are typically on multiple medications 1
• Altered binding in disease states: Structural and functional alterations in albumin occur in liver disease, oxidative stress conditions, and chronic diseases common in cardiovascular patients, potentially affecting drug efficacy and hormone transport 6

Important Caveats

• Hypoalbuminemia effects: Both acute and chronic disorders lead to hypoalbuminemia, which disrupts normal binding and transport of hormones, ions, and drugs, potentially causing edema and multiple metabolic disturbances 2
• Post-translational modifications: Various disease states cause post-translational modifications of albumin that can alter its binding capacity, reducing "effective albumin concentration" even when total albumin levels appear normal 6
• Competition between ligands: Different substances compete for the same binding sites on albumin, which can affect drug distribution and hormone availability in patients taking multiple medications 1, 3