Ketones and lactate

Vivian Imbriotis | June 22, 2026

Ketones and lactate are both alternate energy currencies. Ketones are produced in times of glucose debt, and lactate in times of oxygen debt.

Ketones bodies are alternate forms of energy currency in time of glucose debt. They are

  • Acetoacetate
  • \(\beta\)-hydroxybutyrate
  • Acetone

Normally only \(\beta\)-hydroxybutyrate is measured. Normal value <0.6mM

Production

  • Produced by liver
  • Basaslly produced, production increases in starvation, hypoinsulinaemia, or when intracellular glucose is low

Metabolism - Ketogenesis

  • Glucagon, catecholamines, and suppression of insulin \(\to\) liberation of FFAs from adipose tissue
  • Fatty acids \(\to\) acetyl-CoA
  • In low-glucose conditions, oxaloacetate (final step of Kreb's cycle) is consumed by gluconeogenesis \(\to\) Acetyl-CoA cannot enter Krebs cycle
  • result in Acetyl-CoA accumulation in hepatic mitochondria
  • condensation of 2 acetyl-CoA \(\to\) acetoacetate
  • acetoacetate \(\xrightarrow{reduction}\) \(\beta\)-hydroxybutyrate

Metabolism - Ketolysis

  • Converted back to acetyl-CoA in mitochondria \(\to\) enter Krebs cycle

Role

  • Provide fuel for many extrahepatic cells
  • Can cross BBB \(\to\) supply neurons

Lactate is

  • an organic strong anion
  • an alternate energy currency in times of oxygen debt.

Normal range is <2mM

Production

  • Normally, embden-meyerhof pathway produces pyruvate, and reduces NAD+ to NADH
  • These coenzymes carry electrons that enter electron transport chain \(\to\) serially oxidise cytochrome haemoproteins \(\to\) generate H+ gradient to power ATP synthase (30 ATP/glucose)
  • If oxygen not available as terminal electron acceptor \(\to\) electron transport chain halts, NADH accumulates \(\to\) no NAD+ available for anaerobic glycolysis
  • Pyruvate \(\to\) lactate oxidises NADH \(\to\) allows anaerobic glycolysis to continue (producing 2 ATP/glucose)
  • Constantly produced in RBCs which rely exclusively on Embden-Meyerhof (no mitochondria)
  • \(\beta_2\) agonism \(\to \ \uparrow\)glycolysis \(\to \ \uparrow\)pyruvate \(\to\) shunting into lactate

Metabolism

  • Once oxygen available, converted back to pyruvate in mitochondria
  • In heart, skeletal muscle, immediately enters Krebs cycle for energy (28 ATP).
  • In liver, lactate \(\to\) pyruvate \(\xrightarrow{eventually}\) G6P \(\to\) gluconeogenesis (Cori cycle)

Role

  • Alternate energy source for myocardium, brain
  • Lactate sink - allow a period of ongoing ATP generation when oxygen or Kreb's cycle temporarily interrupted
  • Signalling molecule - e.g. mediate metabolic autoregulation of microcirculation