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Acetoacetic acid (Acetoacetate)

SI UNITS (recommended)

CONVENTIONAL UNITS

Synonym
Acetoacetic acid, diacetic acid, 3-Oxobutanoic acid

Units of measurement
mmol/L, µmol/L, mg/L, mg/dL, mg/100mL, mg%, µg/mL

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Acetoacetic Acid (Acetoacetate)

Synonyms

  • Acetoacetate
  • AcAc
  • β-Ketoacid
  • Acetoacetic acid
  • Ketone body (one of the three major ketones)

Units of Measurement

mmol/L, µmol/L, mg/L, mg/dL, mg/100mL, mg%, µg/mL

Description

Acetoacetic acid (Acetoacetate) is one of the three major ketone bodies, along with β-hydroxybutyrate (BHB) and acetone. It is produced in the liver from the breakdown of fatty acids during states of low carbohydrate availability.

It is an important biochemical marker in:

  • Diabetic ketoacidosis (DKA)
  • Alcoholic ketoacidosis
  • Starvation ketosis
  • Ketogenic diet monitoring
  • Inborn errors of metabolism

Acetoacetate is relatively unstable, converting spontaneously to acetone or BHB. Hence, β-hydroxybutyrate is often preferred for DKA monitoring, but AcAc remains important in urine ketone dipstick testing (nitroprusside method).

Physiological Role

Acetoacetate is a primary alternative energy substrate produced when glucose availability is low.
Its formation occurs in hepatic mitochondria and depends on:

  • Fatty acid oxidation
  • Low insulin levels
  • High glucagon
  • High NAD+/NADH ratio

It is transported to peripheral tissues (brain, muscle, heart), where it is reconverted to Acetyl-CoA and enters the TCA cycle to generate ATP.

Clinical Significance

Elevated Acetoacetate

Occurs in:

  • Diabetic Ketoacidosis (DKA)
  • Starvation / prolonged fasting
  • Alcoholic ketoacidosis
  • Low-carbohydrate or ketogenic diets
  • Pregnancy ketosis
  • Salicylate poisoning
  • Inborn errors of metabolism (e.g., ketothiolase deficiency)

Low Acetoacetate

Not clinically significant alone; seen in:

  • Adequate glucose availability
  • Early treatment of DKA (BHB → AcAc conversion)
  • High NADH states where BHB predominates

Reference Intervals

(Tietz 8E + Mayo Clinic + IFCC verified ranges)

Sample TypeNormal Range
Blood (serum)< 0.3 mmol/L
Moderate ketosis0.3 – 1.0 mmol/L
Ketoacidosis> 1.0 mmol/L
Urine (semiquantitative dipstick)Negative to trace in healthy individuals

Please note:

  • β-hydroxybutyrate levels rise higher than AcAc in severe DKA.
  • Nitroprusside dipsticks detect AcAc primarily (not BHB).

Analytical Notes

1) Nitroprusside Test

Urine dipstick and some serum methods detect Acetoacetate, turning purple in presence of AcAc.
It does not detect β-hydroxybutyrate.

2) Stability

Acetoacetate is chemically unstable and spontaneously decarboxylates into acetone.
Hence:

  • Fresh samples are essential
  • Avoid standing or heat exposure
  • Serum testing preferred in urgent clinical scenarios

3) Preferred Test in DKA

Serum β-hydroxybutyrate is more accurate, as BHB/AcAc ratio increases significantly during severe ketosis.

Units Description & Conversion Factors

Molecular Weight of Acetoacetate ≈ 102.09 g/mol

Unit Meanings

UnitMeaning
mmol/Lmillimole per liter
µmol/Lmicromole per liter
mg/Lmilligram per liter
mg/dLmilligram per deciliter
mg/100mLequivalent to mg%
mg%milligram per 100 mL
µg/mLmicrogram per milliliter

Conversions

  • mg/dL → mg/L: ×10
  • mg/dL → mmol/L:
    mmol/L=mg/dL10.209\text{mmol/L} = \frac{\text{mg/dL}}{10.209}mmol/L=10.209mg/dL​
  • mmol/L → mg/dL:
    mg/dL=mmol/L×10.209\text{mg/dL} = \text{mmol/L} \times 10.209mg/dL=mmol/L×10.209
  • µmol/L → mg/L:
    mg/L=µmol/L×0.10209\text{mg/L} = \text{µmol/L} \times 0.10209mg/L=µmol/L×0.10209
  • mg/L → µmol/L:
    µmol/L=mg/L0.10209\text{µmol/L} = \frac{\text{mg/L}}{0.10209}µmol/L=0.10209mg/L​

Clinical Pearls

  • In DKA, β-hydroxybutyrate rises first, then converts to AcAc during recovery.
  • A negative urine dipstick does not exclude DKA, especially if BHB predominates.
  • Ketosis during fasting is typically mild (<1 mmol/L).
  • Urine ketones lag behind serum ketone changes by several hours.
  • Disorders of fatty acid oxidation may show low ketones even in severe illness.

Interesting Medical Fact

Acetoacetate was the first ketone body discovered (1884). Early diabetic ketoacidosis diagnosis relied solely on detecting AcAc in urine before blood ketone testing was invented.

SEO Unit Converter Text

Acetoacetate unit converter for clinical laboratories. Convert Acetoacetic acid levels between mmol/L, µmol/L, mg/L, mg/dL, mg%, and µg/mL using molecular weight–based formulas. Includes ketosis and ketoacidosis reference intervals and clinical interpretation.

References

MedlinePlus (NIH) — Ketones in blood and urine.

Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition — Ketone Bodies section.

Mayo Clinic Laboratories — Ketone, Serum & Urine Testing.

IFCC Guidelines — Ketone Measurement and Interpretation.

ARUP Consult — Diabetic Ketoacidosis Diagnostic Markers.

American Diabetes Association — DKA diagnostic criteria.

Ketoacidosis biochemistry: Cahill GF. Ketosis physiology.

Last updated: December 5, 2025

Reviewed by : Medical Review Board

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