24B06: Exam Report

Describe the following with respect to lactate:

(a) production (40% of marks).
(b) metabolism (30% of marks).
(c) and its role (30% of marks).

59% of candidates passed this question.

A good description of lactate production should include the sites of production with some estimate of daily production.

In addition, it was expected that answers would cover synthesis via glycolysis, pentose- phosphate pathway (HMP shunt), the chemical reaction catalysed by LDH along with conversion of NADH to NAD.

Lastly an explanation of the mechanisms other than anaerobic conditions that lead to an increased lactate production was required.

The expected information for metabolism included an overview of hepatic uptake and the Cori cycle, the role of renal metabolism and excretion and mitochondrial tissue handling.

With regards to its role, marks were awarded for a discussion of its use as a fuel for cells (including the myocardium, erythrocytes, astrocytes and skeletal muscle).

Lactate’s role as a neurotransmitter and in autoregulation including cerebral vasculature rounded out this section.

Pvi / 24B06: Describe the following with respect to lactate

Part A - Production

Lactate is

End product of anaerobic metabolism

Physiological role

Regenerates NAD+ > maintains glycolysis

Mechanism of production

When NADH and pyruvate are unable to enter Krebs cycle in the absence of oxygen > Pyruvate + NADH + H+ > Lactate + NAD+

Loss of energy potential

  • One molecule of glucose produces 2 ATP anaerobically vs 26 aerobically

Estimate of production

  • ~ 1500 mmols / day or 0.8mmol / kg / hr

  • Blood levels resting value of 1–1.5 mmol / L to a peak of 10–15 mmol / L

Mechanisms of synthesis

Physiological

  • Normal generation of lactate in anaerobic tissues (e.g. RBC-Embden-Meyerhoff pathway , cornea)
  • Glycolysis, pentose-phosphate pathway (HMP shunt), the chemical reaction catalyzed by LDH along with conversion of NADH to NAD

Pathological

  • Defects of oxidative phosphorylation
  • PDH inactivity
  • Sepsis

Non-anaerobic conditions

  • Increased rate of glycolysis- circulating catecholamines, exercise
  • Unregulated entry of substrate into glycolysis

Part B - Metabolism

Sites

  • Liver, muscle, kidneys
  • Hepatic uptake and the Cori cycle: fate of 80 % circulating lactate
Cori cycle: glucose and lactate between liver and muscle.

Part C - And its role

Lactate sink

 Allows for ongoing ATP production from glycolysis during hypoxia

Gluconeogenesis

Mmitochondrial oxidation back to pyruvate> Krebs cycle

(muscle, heart, and brain)

Normal source of energy in anaerobic tissues

RBCs, cornea

Major fuel during exercise

Marker of tissue hypoxia

Neurotransmitter produced by glial cells

(Especially astrocytes) > lactate then shuttled to neurons to support their energy requirement by the astrocyte-neuron-lactate shuttle > Lactate is fundamental fuel to support myelinated axons and attenuates neurotransmission, especially of GABA

Role in metabolism

Inhibits lipolysis

Author: Nazma Navilehal Rajasab