# Rethinking Human Energy Metabolism

## TL;DR

This paper reviews how glycolysis and mitochondrial processes work together, with lactate playing a key role in energy metabolism.

## Contribution

The paper proposes that fatty acid β-oxidation and glycolysis form an interdependent energy metabolism system in humans.

## Key findings

- Obligate lactate formation during glycolysis enhances the TCA cycle's anaplerotic functions.
- Fatty acid β-oxidation is essential for lactate production, which supports mitochondrial respiration.
- Lactate acts as an emergency energy substrate for the heart, muscles, and brain.

## Abstract

For a long time, glycolysis and mitochondrial oxidative phosphorylation were opposed to each other. Glycolysis works when there is a lack of oxygen; the mitochondria supply ATP in an oxygen environment. In recent decades, it has been discovered that glycolysis in vivo always works and the final product is lactate. Lactate can accumulate and is the transport form for pyruvate. In this review, we look at how obligate lactate formation during glycolysis affects the tricarboxylic acid (TCA) cycle and mitochondrial respiration. We conclude that fatty acid β-oxidation is a prerequisite for obligate lactate formation during glycolysis, which in turn promotes and enhances the anaplerotic functions of the TCA cycle. In this way, a supply of two types of substrates for mitochondria is formed: fatty acids as the basic energy substrates, and lactate as an emergency substrate for the heart, skeletal muscles, and brain. High steady-state levels of lactate and ATP, supported by β-oxidation, stimulate gluconeogenesis and thus support the lactate cycle. It is concluded that mitochondrial fatty acids β-oxidation and glycolysis constitute a single interdependent system of energy metabolism of the human body.