Describe the formation and the metabolic fate of lactate. Outline its role in energy
It was expected that the answer would include comments on lactate generation from glucose via
pyruvate and the metabolic linkage of nicotinamide adenine dinucleotide (NAD). Lactate
(pyruvate is reduced to lactate while NADH is oxidized to NAD+ ). The citric
acid cycle and the electron transport chain occur in the mitochondria of cells, and will only
proceed in the presence of oxygen.
One molecule of glucose produces 2 ATP anaerobically (pyruvate to lactate) vs 26 aerobically
(pyruvate enters TCA cycle) .Total production is about 1500 mmols/day with blood levels resting
value of 1–1.5 mmol/L to a peak of 10–15 mmol/L.
Lactate can be used in 3 ways:
1. Conversion to glucose via gluconeogenesis in the liver and release back into circulation
(Cori cycle). This is the fate of 80 % circulating lactate from tissues low in oxygen (e.g.
exercising muscle with low pO2) or red blood cells (no mitochondria). The production
from glucose in RBC’s is the Embden-Meyerhoff pathway.
2. Consumed as a fuel e.g. heart (20% of circulating lactate)
3. Mitochondria and oxygen
Oxidation back to pyruvate by well-oxygenated muscle cells, heart cells, and brain
cells pyruvate is then directly used to fuel the Krebs cycle (generating 28 mmols
Lactate generation from muscle is increased with B1 mediated stimulation e.g. from adrenalin.
This topic is well covered in Power and Kam Principles of Physiology for the Anaesthetist, 3rd
Edition, although some of the details are in several different sections.
Most candidates showed some understanding of the role of glucose in the production of
pyruvate to lactate. However, the differential ATP production, the role of NADH availability and
how oxygen and the role of mitochondria were involved was less well handled. Better answers
described the normal generation of lactate in some tissues (e.g. RBC) and role of muscle and
liver in metabolism back to glucose (Cori cycle) and the role of lactate as a metabolic substrate
in some organs. Marks were awarded for normal production values and blood levels.