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Cystine
(Oxidized Dimer of Cysteine – Key Marker for Cystinuria & Amino Acid Metabolism)
Synonyms
- Cystine
- Cys–Cys (oxidized cysteine dimer)
- Dibasic amino acid
- Sulfur amino acid dimer
Units of Measurement
- µmol/L
- mg/L
- mg/dL
- mg/100 mL
- mg%
- µg/mL
1 mg/L = 0.1 mg/dL
1 µg/mL = 1 mg/L
mg/dL = mg% = mg/100 mL
Description
Cystine is the oxidized dimer of two cysteine molecules linked via a disulfide bond (S–S).
It appears in the blood and urine as part of normal sulfur amino acid metabolism.
Clinically, cystine is most important as a biomarker for cystinuria and cystine kidney stones - one of the few amino acids that forms insoluble crystals in urine.
Physiological Role
- Formed by oxidation of cysteine
- Helps stabilize proteins through disulfide bonding
- Significant structural component of keratin (hair, nails, skin)
- Present in plasma, tissues, and urine
- Regulated by cystine/cysteine redox balance
Clinical Significance
High Cystine (Hyper-cystinuria)
The most important clinical condition related to cystine elevation.
1. Cystinuria (Primary Use)
A genetic disorder (SLC3A1 or SLC7A9 mutations) involving defective renal tubular reabsorption of:
- Cystine
- Lysine
- Arginine
- Ornithine
Collectively called COLA amino acids.
Cystine is the least soluble, leading to:
- Recurrent kidney stones
- Early-onset urolithiasis
- Staghorn calculi
- Recurrent UTIs
2. Cystine Stones
High cystine in urine → hexagonal cystine crystals.
Serum cystine may be normal; urine cystine is key for diagnosis.
3. Oxidative Stress Disorders
Increased cystine relative to cysteine indicates:
- Oxidative stress
- Systemic inflammation
- Aging processes
4. Renal Tubular Disorders
Tubular dysfunction may cause elevated urinary cystine.
Low Cystine (Rare)
May be seen in:
- Malnutrition
- Severe oxidative stress (cysteine depletion → low cystine)
- Metabolic disorders involving sulfur metabolism
- After cystine-binding drug therapy (tiopronin, D-penicillamine)
Usually not clinically significant.
Reference Intervals
(Tietz 8E + LC-MS/MS Amino Acid Panels + Mayo + ARUP)
Fasting Plasma Cystine
- 40 – 70 µmol/L (typical adult range)
Ranges vary slightly by lab and age.
Urine Cystine (Primary Diagnostic Test)
- <30 mg/day: Normal
- >250–300 mg/day: Cystinuria
- >500 mg/day: Severe cystinuria
Special tests:
- Sodium nitroprusside test (qualitative)
- Urinary cystine saturation index
Diagnostic Uses
1. Cystinuria Diagnosis (Primary Use)
- Detects excess cystine → identifies patients prone to cystine stones.
- Urine cystine is much more diagnostic than plasma.
2. Kidney Stone Workup
- Hexagonal crystals on microscopy confirm cystine stones
- Quantitative urine cystine monitors:
- Treatment response
- Thiol therapy effectiveness
- Hydration adequacy
- Treatment response
3. Metabolic Disorders
Cystine levels are assessed in:
- Aminoacidopathies
- Oxidative stress studies
- Disorders of sulfur metabolism
4. Nutritional & Redox Status
Altered cystine-to-cysteine ratio indicates:
- Poor antioxidant status
- High oxidative load
Analytical Notes
- Fasting plasma preferred
- Plasma must be deproteinized promptly to prevent oxidation/reduction changes
- LC-MS/MS is gold standard
- Cystine is sensitive to sample handling and storage
- Urine tests require acidified samples for stability
Clinical Pearls
- Cystinuria = high urine cystine, NOT high plasma cystine.
- Hexagonal crystals in urine are almost pathognomonic for cystine stones.
- Cystine stones require urine alkalinization, high fluid intake, and sometimes thiol agents (tiopronin, D-penicillamine).
- Cystine is much less soluble at acidic urine pH - keep urine pH >7.0–7.5 to prevent stone formation.
- Plasma cystine-to-cysteine ratio is a marker of oxidative stress.
Interesting Fact
Cystine stones are radiodense on CT due to sulfur content - unlike uric acid stones, which are radiolucent.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Amino Acids.
- Mayo Clinic Laboratories - Plasma & Urine Amino Acids.
- ARUP Consult - Amino Acid Disorders & Kidney Stone Analysis.
- AUA/EAU Kidney Stone Guidelines.
- Inborn Errors of Metabolism Clinical Guidelines.
- MedlinePlus / NIH - Amino Acids & Kidney Stones.