glycine
Summary
Glycine is the smallest amino acid and serves dual roles as an inhibitory neurotransmitter in the spinal cord/brainstem and as a building block for proteins, heme, purines, glutathione, and creatine. It acts on glycine receptors (Cl- channels) to cause hyperpolarization, and also functions as a co-agonist at NMDA receptors. Clinically relevant in glycine encephalopathy, strychnine poisoning, and TURP syndrome (glycine irrigation toxicity).
Detail
Glycine is a non-essential amino acid with the simplest structure (H2N-CH2-COOH), lacking a chiral center. It has two major physiological roles:
1) Inhibitory neurotransmission: Glycine binds ionotropic glycine receptors (GlyR), ligand-gated chloride channels, primarily in the spinal cord and brainstem, causing hyperpolarization and inhibition of motor neurons (important for reciprocal inhibition of antagonist muscles, e.g., Renshaw cells). Strychnine is a glycine receptor antagonist that causes muscle rigidity, hyperreflexia, and lockjaw-like spasms due to loss of inhibitory tone—clinically mimics tetanus but strychnine poisoning classically spares the ability to have intervals of relaxation and involves ascending paralysis-like rigidity with sensorium preserved.
2) Co-agonist at NMDA receptors: Glycine (and D-serine) bind the NMDA receptor at a site distinct from glutamate, required for channel activation—relevant to excitatory neurotransmission and long-term potentiation.
Biosynthetic roles: Glycine is a precursor for porphyrin/heme synthesis (combines with succinyl-CoA via ALA synthase), purine synthesis, creatine, and glutathione. It is also conjugated with bile acids (glycocholic acid) and with certain drugs/toxins for excretion (e.g., benzoic acid to hippuric acid).
Clinical correlations: - Glycine encephalopathy (nonketotic hyperglycinemia): autosomal recessive inborn error of glycine cleavage system causing accumulation of glycine, presenting in neonates with lethargy, hypotonia, myoclonic seizures, and burst-suppression EEG pattern; poor prognosis. - TURP syndrome: glycine-containing irrigation fluid used in transurethral resection of prostate can be absorbed systemically, causing hyponatremia, visual disturbances (glycine is a retinal neurotransmitter, causing transient blindness), and hyperammonemia (from glycine metabolism). - Strychnine poisoning: antagonizes glycine receptors, causing severe muscle spasms and risk of respiratory failure; treat with benzodiazepines.
Glycine is often tested in the context of neurotransmitter physiology, inborn errors of metabolism, and pharmacologic toxidromes.
Sources
- First Aid for the USMLE Step 1
- Lippincott Biochemistry
- Katzung's Basic and Clinical Pharmacology
- Robbins Basic Pathology
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