Humans can synthesize 11 of the 20 standard amino acids from scratch. The other 9 are essential - they must come from the diet because we lack the enzymes to synthesize them.
The Nine Essential Amino Acids
Amino acid
One-letter
Phenylalanine
F
Valine
V
Threonine
T
Tryptophan
W
Isoleucine
I
Methionine
M
Histidine
H
Leucine
L
Lysine
K
Conditionally Essential
Some amino acids are nonessential in adults but essential during periods of rapid growth, illness, or specific conditions: arginine, glutamine, and tyrosine (needed from diet when phenylalanine is restricted, as in PKU).
Metabolic Disorders of Amino Acids
Several classic inborn errors of metabolism affect amino acid breakdown. The MCAT occasionally tests recognition.
Result: phenylalanine accumulates, converts to phenylpyruvate and phenyllactate, which damage the developing brain. Intellectual disability if untreated.
Treatment: diet low in phenylalanine (must avoid aspartame), supplement tyrosine.
Newborn screening detects PKU at birth, enabling early dietary management.
Alkaptonuria
Homogentisate oxidase deficiency → homogentisic acid accumulates → dark urine on standing, black connective tissue (ochronosis), arthritis later in life. Famously, one of the first “inborn errors” described by Archibald Garrod.
Maple Syrup Urine Disease (MSUD)
Branched-chain alpha-ketoacid dehydrogenase deficiency → leucine, isoleucine, valine and their alpha-keto acids accumulate. Urine smells like maple syrup. Severe neurological symptoms if untreated.
Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Leucine, Lysine (mnemonic: PVT TIM HALL, where "A" stands for Arginine - conditionally essential). These nine must come from the diet because humans lack the enzymes to synthesize them.
What enzyme is deficient in classic phenylketonuria (PKU), and what is the treatment?
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Phenylalanine hydroxylase (PAH), which normally converts phenylalanine to tyrosine. Without PAH, Phe accumulates and damages the developing brain. Treatment: low-phenylalanine diet (avoid aspartame and most protein-rich foods) combined with tyrosine supplementation. Early diagnosis through newborn screening is essential to prevent intellectual disability.
Why is tyrosine considered conditionally essential in patients with PKU?
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Tyrosine is normally synthesized from phenylalanine by phenylalanine hydroxylase. In PKU, PAH is deficient, so the patient cannot make tyrosine. Tyrosine must be provided in the diet. This is the general principle of "conditionally essential" - a nonessential amino acid becomes essential when its precursor or synthesis pathway is impaired.
