Lactate Levels May be Increased in MECFS. Find out more About How Lactate Effects Physiology and Pathology.

 Lactate is a molecule that is often associated with muscle fatigue and lactic acidosis, but it has many other roles in human health and disease. In this blog post, I will summarize the main findings of a recent review article by Xiaolu Li and colleagues, who explored the diverse functions of lactate in metabolism, signaling and posttranslational modification.

Lactate is produced by glycolysis, the breakdown of glucose into pyruvate, which can then be converted into lactate-by-lactate dehydrogenase (LDH). Lactate can also be converted back into pyruvate by LDH, or into glucose by gluconeogenesis in the liver. Lactate can be transported across cell membranes by monocarboxylate transporters (MCTs), which allow lactate to shuttle between different cells, organs and tissues.

Lactate has been shown to act as a signaling molecule, either by binding to its specific receptor GPR81, or by modulating the activity of other enzymes and proteins. For example, lactate can inhibit histone deacetylases (HDACs), which regulate gene expression by removing acetyl groups from histones. Lactate can also activate hypoxia-inducible factor 1-alpha (HIF-1α), a transcription factor that regulates the expression of genes involved in angiogenesis, glycolysis and cell survival under low oxygen conditions.

Lactate can also modify proteins by adding a lactyl group to lysine residues, a process called lactylation. This is a reversible and dynamic modification that depends on the concentration of lactate and the activity of LDH. Lactylation has been found to affect the function of various proteins, such as histones, p53, NF-κB and STAT3. Lactylation can regulate gene expression, cell proliferation, inflammation and other biological processes.

Lactate plays an important role in various physiological and pathological conditions, such as exercise, diabetes, sepsis, neurodegeneration and cancer. Lactate can have beneficial or detrimental effects depending on the context and the balance between production and consumption. For instance, lactate can enhance muscle performance and recovery during exercise, but it can also contribute to insulin resistance and inflammation in diabetes. Lactate can protect neurons from oxidative stress and excitotoxicity, but it can also promote neuroinflammation and neurodegeneration. Lactate can support tumor growth and survival by providing energy and signaling molecules, but it can also trigger anti-tumor immune responses and apoptosis.

In conclusion, lactate is a multifaceted molecule that has diverse roles in human health and disease. Lactate metabolism, signaling and modification are tightly regulated by various factors and feedback mechanisms. Understanding the molecular mechanisms and functions of lactate may provide new insights and therapeutic opportunities for various diseases.

Lactate metabolism in human health and disease by Xiaoli Li et al