Amino acids

Key facts

The 20 proteinogenic amino acids—each with distinct roles in protein synthesis, signaling, and metabolic pathways tied to repair and longevity.

How many essential amino acids do adults need from food?

Nine are indispensable (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine); the others are synthesized when nitrogen and carbon pools are adequate.

Alanine

Alanine is a glucogenic amino acid that buffers muscle nitrogen and supports hepatic glucose output during fasting.

Adequate dietary protein maintains alanine pools for energy interconversion; severe protein malnutrition lowers lean mass and impairs metabolic resilience—indirect stress on tissue maintenance with age.

Arginine

Arginine fuels nitric oxide synthase and the urea cycle; it supports vascular tone and wound-repair pathways.

NO signaling influences perfusion and immune function; arginine also intersects nucleotide synthesis. Very low protein intake can limit substrate availability for repair-heavy tissues.

Asparagine

Asparagine supports protein N-linked glycosylation and nitrogen transport; asparagine synthetase is critical when diet is low in protein.

Cellular asparagine availability affects protein folding quality control; chronic protein inadequacy stresses biosynthetic pathways that depend on non-essential amino acid synthesis.

Aspartic acid

Aspartate is a urea-cycle and nucleotide-precursor amino acid—central to pyrimidine synthesis alongside folate cofactors.

Nucleotide pools depend on aspartate flux; marginal protein or folate status can constrain both pyrimidine synthesis and the repair capacity that depends on accurate replication.

Cysteine

Cysteine (via cystine) is the rate-limiting substrate for glutathione—primary intracellular defense against oxidative DNA damage.

Glutathione detoxifies electrophiles and supports base-excision repair enzymes in an oxidizing environment. Low cysteine or methionine intake associates with weaker antioxidant defenses and greater oxidative DNA lesions in human studies.

Glutamine

Glutamine is the most abundant free amino acid in blood—fuel for enterocytes, immune cells, and nucleotide synthesis during proliferation.

Rapidly dividing cells (gut lining, lymphocytes) depend on glutamine; chronic catabolic states deplete pools and can impair barrier and immune surveillance of damaged cells.

Glutamic acid

Glutamate is a central nitrogen hub—transamination, neurotransmission (as glutamate/GABA), and precursor to glutamine and proline.

Glutamate metabolism intersects insulin secretion and CNS signaling; adequate protein prevents muscle glutamate drain during fasting. Excess monosodium glutamate as a flavoring is not the same as protein-bound glutamate in whole foods.

Glycine

Glycine supplies the glycine cleavage system and glutathione; it is a major one-carbon donor when serine is limited.

Low glycine availability limits glutathione and can constrain one-carbon flux alongside folate—relevant to nucleotide synthesis and epigenetic maintenance with age.

Histidine

Histidine is essential for hemoglobin, carnosine (muscle pH buffer), and histamine signaling; it chelates metal cofactors in enzymes.

Metal coordination by histidine supports polymerases and repair enzymes that require zinc or iron. Essential status means intake must come from diet when synthesis cannot meet demand.

Isoleucine

Isoleucine is a branched-chain amino acid (BCAA) that activates mTOR and supports muscle protein synthesis.

Preserving lean mass supports metabolic health and physical resilience—indirect protection against frailty and inflammaging. BCAA imbalance without adequate total protein does not replace whole-protein quality.

Leucine

Leucine is the strongest BCAA activator of mTORC1—signaling muscle anabolism and influencing autophagy when chronically excessive.

Sarcopenia prevention depends on protein and leucine-rich meals plus exercise; chronic mTOR overactivation from isolated BCAA megadoses may trade off autophagy quality—context matters for longevity biology.

Lysine

Lysine is essential for collagen cross-linking, carnitine synthesis, and histone methylation/acetylation balance.

Epigenetic marks on histones depend on adequate lysine and one-carbon/methyl donors—linking protein nutrition to chromatin maintenance over the lifespan.

Methionine

Methionine starts every new protein chain and feeds S-adenosylmethionine (SAM)—the universal methyl donor for DNA and histones.

SAM-dependent methylation maintains DNA and histone marks; homocysteine rises when remethylation fails—often from low B12/folate/B6 alongside methionine flux. Balance matters more than extreme restriction in humans.

Phenylalanine

Phenylalanine is essential and hydroxylated to tyrosine—precursor to catecholamines and melanin.

Adequate phenylalanine/tyrosine supports neurotransmitter synthesis; PKU aside, typical diets supply enough for protein turnover and signaling. Tyrosine can partially spare phenylalanine needs.

Proline

Proline-rich motifs dominate collagen; proline hydroxylation requires vitamin C and supports extracellular matrix integrity.

Matrix stiffness and skin/vascular integrity depend on collagen proline hydroxylation—vitamin C deficiency (scurvy) breaks this link. Protein adequacy supports connective-tissue maintenance with age.

Serine

Serine feeds one-carbon metabolism via SHMT—supplying methyl groups for thymidylate and purine synthesis alongside folate.

Serine–folate flux fuels dTMP and purines; low serine or folate status can tighten nucleotide pools relevant to replication fidelity—adjacent to uracil misincorporation risk when thymidylate is scarce.

Threonine

Threonine is essential for mucin glycoproteins, collagen, and immune proteins; it supports gut barrier integrity.

Barrier tissues turn over rapidly; threonine inadequacy with low protein intake can impair mucin production and immune protein synthesis—indirect defense against systemic inflammation.

Tryptophan

Tryptophan is the precursor to serotonin, melatonin, and the NAD+ salvage pathway via kynurenine.

NAD+ supports PARP-dependent DNA repair and sirtuin signaling; sleep/melatonin from tryptophan intersect circadian DNA-damage repair timing. Very low protein can limit both pathways.

Tyrosine

Tyrosine is the precursor to dopamine, norepinephrine, and epinephrine—and to melanin and thyroid hormone (via iodination).

Catecholamines influence stress responses and metabolic rate; adequate tyrosine/phenylalanine prevents deficiency in neurotransmitter synthesis during high stress or cold exposure—not a primary DNA-repair lever, but supports whole-system resilience.

Valine

Valine is a BCAA oxidized in muscle for energy and gluconeogenic precursors during exercise and fasting.

BCAAs preserve muscle during caloric deficit when total protein is adequate; isolated valine supplementation without training context offers little longevity-specific benefit.