Human Physiology: Systemic Circulation and Amino Acid Regulation

Amino Acid Metabolism

• Amino acid concentration in blood is kept relatively constant, similar to glucose concentration.
• Amino acids are used in the liver for protein synthesis and energy production.

Amino Acid Metabolism - Degradation

• In the liver, amino acids are catabolized into ammonia (NH3)/urea (amine part of AA) and α-keto acids (the carbon skeletons of AA).
• The carbon skeletons of α-keto acids are converted to common intermediates of energy-producing metabolic pathways.
• These intermediates can be metabolized by central pathways of metabolism (e.g., gluconeogenesis, glycolysis, TCA cycle) to produce ATP, CO2, and H2O.
• Excess amino acids are rapidly degraded, as they are not stored in the body.

Amino Acid Characteristics

• Amino acids with charged side chains (basic or acidic) have a proton acceptor or donor function.
• At physiological pH, the side chains of these amino acids are fully ionized and positively charged.
• Histidine's side chain can be either positively charged or neutral, depending on the environment's pH, and plays an important function as a buffer.

Non-Polar and Polar Amino Acids

• Non-polar amino acids are located in the interior of soluble proteins and in membrane proteins.
• Polar amino acids are located on the surface of soluble proteins and in the hydrophilic regions of membrane proteins.

Amino Acid Derivatives

• Tyrosine derivatives: triiodothyronine (T3), thyroxine (T4), dopamine, and melanin.
• Taurine derivatives: bile acids.
• Glutamate derivatives: GABA (inhibitory neurotransmitter).
• Tryptophan derivatives: serotonin (neurotransmitter).
• Histidine derivatives: histamine (mediator of allergic reactions).
• Lysine derivatives: carnitine (involved in lipid oxidation).

Peptides with Physiological Relevance

• Oxytocin: a 9-amino acid peptide hormone produced in the hypothalamus, involved in uterine contractions and milk secretion.
• Antidiuretic hormone (ADH): a 9-amino acid peptide produced in the hypothalamus, essential for maintaining water balance.
• Creatine: a tripeptide involved in energy production in muscle and cardiac cells.
• Bradykinin: a 9-amino acid peptide, vasoactive substance.
• Angiotensin II: a 10-amino acid peptide, potent vasoconstrictor.

Protein Digestion and Amino Acid Metabolism

• Unlike fats and carbohydrates, amino acids are not stored by the body.
• Amino acids must be obtained from the diet, released through the degradation of body protein, or synthesized de novo from intermediate metabolites.
• Protein digestion starts in the stomach, where gastric juice (HCl and pepsinogen) breaks down proteins into peptides and amino acids.
• In the small intestine, pancreatic enzymes continue to break down proteins into absorbable peptides and amino acids.
• The liver plays a crucial role in regulating blood amino acid concentrations during periods of amino acid absorption.

Fate of Dietary Amino Acids after Absorption

• Most amino acids are removed by the liver on "first pass" (Hepatic Portal Circulation), never reaching the general circulation.
• The liver helps keep blood amino acid concentrations stable during periods of amino acid absorption.

Urea Cycle

• Ammonia is very toxic to the brain, and the body needs to keep its levels very low in plasma.
• In mammals, little free ammonia is excreted in urine; instead, it is converted to urea through the urea cycle.
• The urea cycle is the most important route for disposing of nitrogen from the body.
• Urea is excreted by the kidneys in urine.

Blood Urea Nitrogen (BUN)

• BUN is roughly one-half of the blood urea, measured by assaying the nitrogen component of urea.
• The BUN is an important parameter in evaluating kidney function.