Biomedical Importance of Amino Acids

Some proteins contain amino acids that have been modified after translation.
Carboxylation of glutamate to form γ-carboxyglutamate allows for Ca²⁺ binding.
Hydroxylation of proline forms a collagen triple helix.
Hydroxylation of lysine to 5-hydroxylysine strengthens maturing collagen fibers.
Amino acids are precursors to biologically important molecules: heme, purines, pyrimidines, hormones, neurotransmitters, and bioactive peptides.
Neurotransmitters derived from amino acids include γ-aminobutyrate (GABA), 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine.
Several neurologic and psychiatric drugs act on these neurotransmitters.

Alanine carries ammonia and carbons from pyruvate in skeletal muscle to the liver through the Cori cycle.
Together with glycine, it is one of the most abundant free amino acids in the plasma.

Arginine is a carrier of nitrogen atoms in urea biosynthesis.
The guanidino group of arginine is incorporated into creatine.
Arginine is converted to ornithine.
The carbon skeleton of ornithine becomes that of putrescine and spermine.
Nitric oxide synthase converts the guanidino group of arginine to L-ornithine and nitric oxide.

Cysteine is used in the biosynthesis of coenzyme A after it reacts with pantothenate to form 4-phosphopantothenoylcysteine.
Taurine displaces coenzyme A from cholyl-CoA to form taurocholic acid.

Glycine conjugation creates water-soluble metabolites (e.g., benzoate to hippurate) excreted in the urine.
Glycine is incorporated into creatine.
The nitrogen and α-carbon of glycine contribute to the pyrrole rings and methylene bridge carbons of heme.
The entire glycine molecule becomes atoms 4, 5, and 7 of purines.

Histidine is a precursor to histamine, a biogenic amine involved in allergic reactions and gastric secretion.
Histidine decarboxylase catalyzes histamine synthesis.
Other histidine derivatives include carnosine, ergothioneine, and anserine.
Carnosine (β-alanylhistidine) and homocarnosine (γ-aminobutyryl-histidine) are major constituents of excitable tissues, brain, and skeletal muscle.
Low urinary levels of 3-methylhistidine indicate Wilson disease.

S-adenosylmethionine (SAM) is the primary source of methyl groups in the body.
SAM is formed from methionine and ATP, catalyzed by methionine adenosyltransferase (MAT).
Decarboxylation of SAM produces polyamines spermine and spermidine which are important for:
- Cell proliferation and growth
- Growth factors for cultured mammalian cells
- Stabilizing intact cells, subcellular organelles, and membranes

Serine is a precursor to sphingosine, purines, and pyrimidines.
Serine provides carbons 2 and 8 of purines and the methyl group of thymine.
Homocystinuria is caused by genetic defects in cystathionine β-synthase (PLP dependent) that leads to the inability to convert serine and homocysteine to cystathionine and water.
Serine is a precursor to peptidyl selenocysteine.

Tryptophan is a precursor to serotonin (5-hydroxytryptamine).
Serotonin is produced by hydroxylation of tryptophan by liver tryptophan hydroxylase, followed by decarboxylation.
Serotonin is a potent vasoconstrictor and stimulator of smooth muscle contraction.
Carcinoid syndrome involves the overproduction of serotonin by tumor cells.
Melatonin is synthesized by N-acetylation of serotonin, followed by O-methylation in the pineal body.
The main urinary catabolites of tryptophan include 5-hydroxyindoleacetate and indole-3-acetate.

Tyrosine is a precursor to dopamine, norepinephrine, and epinephrine.
These catecholamines are neurotransmitters involved in regulating mood, attention, and heart function.
The production of the catecholamines involves a series of enzymatic steps, starting with the hydroxylation of tyrosine to L-DOPA.

The phosphorylation and dephosphorylation of specific seryl, threonyl, or tyrosyl residues of proteins play a crucial role in regulating the activity of enzymes involved in lipid and carbohydrate metabolism.
They also contribute to signal transduction cascades.

Creatine is primarily formed in muscle from creatine phosphate.
Creatinine is the result of an irreversible, nonenzymatic dehydration and loss of phosphate from creatine phosphate.
The 24-hour urinary excretion of creatinine reflects muscle mass.
Creatine synthesis requires glycine, arginine, and methionine.
The final step in the synthesis is the methylation of guanidoacetate by SAM.

β-Alanine is produced during the catabolism of uracil.
β-Aminoisobutyrate is produced during the catabolism of thymine.
β-Alanine can be produced by the hydrolysis of β-alanyl dipeptides by carnosinase.
β-Aminoisobutyrate is formed by the transamination of methylmalonate semialdehyde.

Carnosine and anserine (N-methylcarnosine) activate myosin ATPase, chelate copper, and enhance copper uptake.
Β-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle.
Carnosinase deficiency is a heritable disorder leading to carnosinuria.
Homocarnosine is found in the human brain at higher levels than carnosine.
Homocarnosine is a significant source of γ-aminobutyrate (GABA), a major inhibitory neurotransmitter in the brain.