Thread by @MVAitor

Here we go with some random-interesting facts about lactate and metabolism. A dynamic threat where everybody can add interesting info. (following the order) about lactate and its implication in exercise, health, and disease metabolism.
#Lactatefacts by @Glut4Science and @MVAitor

Let´s start learning!

1- Glycolysis byproduct that can be produced and utilized by various (almost every) body cell.
2- Highly dynamic metabolite as it can "travel" through different intra-extra cellular compartments.

#Lactatefacts by @Glut4Science and @MVAitor

3-LDH enzyme is responsible for its oxidation and reduction to pyruvate. But it has more affinity to Pyruvate? WTF!
4.1-MCT proteins "family" in charge of its transport in different tissues (different isoforms). Specific for L-Lactate

#Lactatefacts by @Glut4Science and @MVAitor

4.2- MCTs are not only for L-lactate, but also other metabolites like pyruvate or Ketone Bodies (higher Km than Lactate, by the way).
5- ILS (intracellular lactate shuttle) + Cell-Cell lactate shuttle hypothesis support its dynamism.

#Lactatefacts by @Glut4Science and @MVAitor

6.1- It´s produced mainly in Type II fiber (highly glycolytic)
6.2- Consumed in Type I & IIa fibers = oxidation; Type IIx = glycogenesis).
6.3- It all depends on pH, muscle metabolic rate, blood flow, etc.

#Lactatefacts by @Glut4Science and @MVAitor

7- Heart´s mitochondria are big consumers of Lactate, especially during exercise.
8- Neurons can use it (preferably to others) as a fuel source: glycolysis or glycogenesis. The brain EATS lactate!

#Lactatefacts by @Glut4Science and @MVAitor

9- Skeletal muscle is the main lactate producer and consumer tissue, especially during exercise = the lactate fabric.
10- High [La-] downregulates glycolytic flux decreasing PFK´s and hexokinase´s activities.

#Lactatefacts by @Glut4Science and @MVAitor

11.1- Lactate is not only a fuel source but also a major gluconeogenic metabolite (liver, mainly).
11.2- And even a signalling molecule with important implications in metabolism and protein transcription.

#Lactatefacts by @Glut4Science and @MVAitor

11.3- It could play an important role in mitochondrial dynamics by stimulating mito. biogenesis. Exercise, training, production and oxidation, Z2, Fat max, blood [La-] and flux, eating carbohydrates... = all related concepts😊

#Lactatefacts by @Glut4Science and @MVAitor

12- It’s very difficult to compare absolute values of blood [La-] between individuals, but… the avg value among all elite/pro athletes I have tested in cycling and running, at VT1 intensity (~FatMax/slightly lower) is ~1,6mmol/L.

#Lactatefacts by @Glut4Science and @MVAitor

13- Lactate can also influence food behavior around exercise. Post-exercise appetite depression was associated with higher blood [La-] mediated by changes in GLP-1, PYY, and acylated-ghrelin. These peptides/hormones regulate appetite.

#Lactatefacts by @Glut4Science and @MVAitor

14-⬆️lactate flux in mitochondria can inhibit fatty acid lipolysis in peripheral tissues, transport into the inner membrane, and even beta-oxidation in TCA cycle.This happens through the regulation of CPT1, Malonil CoA, and Acetyl CoA.

#Lactatefacts by @Glut4Science and @MVAitor

15-As seen in some previous points, lactate can be a strong signalling metabolite in several cells/tissues. The tumoral cell is one of those environments where lactate plays an important signalling role. Check👇🏼

#Lactatefacts by @Glut4Science and @MVAitorfrontiersin.org/articles/10.33…

16- We can´t find "lactic acid" in physiological pH, so we should speak about "lactate" in the human body. In fact, our "lactate" concept refers to L-Lactate enantiomer, not D-Lactate (it could even be negative for the body).

#Lactatefacts by @Glut4Science and @MVAitor

@Glut4Science 17- Lactate has the capacity to regulate its own metabolism. It’s so cool!

The questions that arises: why has lactate this power?



#Lactatefacts by @Glut4Science and @MVAitorsciencedirect.com/science/articl…

@Glut4Science 18- A VERY important #Lactatefacts:

Lactate is the primary source of carbons for the TCA (our main energy producing pathway), and, therefore, the MAIN source of energy for the body🤯. Lactate showed the higher turnover flux among different carbon metabolites.
Hui S, et al. 2017.