Lactate Dehydrogenase Information

Enzyme Name

Lactate Dehydrogenase

Reaction Catalyzed

Oxidation/Reduction Pyruvate is reduced to Lactate OR Lactate is oxidized to Pyruvate

Reaction Type

Redox Reaction

Pathway Involvement

As pointed out it is not officially part of either Glycolysis or Gluconeogenesis The reaction is necessary however to support glycolysis under anaerobic conditions.

As a side note... in bacteria the lactate is excreted into the media - if the media happens to be milk then the lactate lowers the pH of the milk - the milk proteins denature and coagulate, it gels and we eat it because it tastes good - it is called Yogurt.

In mammals muscle cells can do this - the lactate is excreted into the blood stream. it is taken up by the liver (mostly) and regenerated into glucose (via gluconeogenesis)

Red blood cells also use this process. RBCs do not have much of a need for metabolism and do not have mitochondria (or a nucleus for that matter). They depend on lactate fermentation for all their (limited) energy needs.

Cofactors/Cosubstrates

NADH/NAD⁺ is a cosubstrate/coproduct

Rationale

Glycolysis as it ends with Pyruvate is a net oxidation. One reaction, Glycerate Kinase, Oxidized an aldehyde to an organic acid with the concomitant reduction of NAD⁺ to NADH.

NAD⁺ Represents the primary cytosolic electron carrier and is in very limited supply. If there was no way to re-oxidize it then net glycolysis would soon cease for lack of an available electron carrier.

WE have oxygen (you will be dragged over the coals on this next module). So What do anaerobic bacteria do - or even more importantly what do YOU do when you excersize heavily and utilize energy faster than you can transport molecular oxygen to the muscles.

By the way, this is why your muscles are sore after a hard excersize; all that lactate accumulation lowers cellular pH and it takes a while to transport all of it back out of the cell

It turns out this reaction is a good answer. It takes the NADH that was generated earlier and now dumps it into pyruvate in a very favorable reaction to produce lactate and return NAD⁺.

As you can see below from the thermodynamics below, this allows for accumulation of lactate up to 24,000 times higher than pyruvate before it generates problems with the energy profile.

Bacteria, simply dump the lactate out of the cell into the environment - thus they can keep this up for a long time. There is one caveat. Lactate is an acid and if the bacteria are in a "small" volume, then the pH of the solution starts to decrease. While this is potentially bad for the bactria -it can be good for us...We take advantage of exactly this when we make yogurt. We grow Lactobacillus acidophilus in milk until the pH drops so low that all the proteins denature and precipitate. The goo left behind is a bit sour (as all acids are) so we put some fruit in it and eat.... YUM!

Red Blood Cells contain neither a nucleus not mitochondria. for the little amount of ATP that they require they depend on this reaction to generate it.

ΔG^o'

-25.2 kJ/M

K_eq

Comments

Starting from standard state and allowing the reaction to come to equilibrium the lactate concentration would end up ~24,000 times higher than the pyruvate

The Standard Free Energy favors lactate production.

Note: the Standard Free Energy greatly favors production of Lactate and NAD⁺.

"In cell" Substrate Concentrations^*

S₁ =

S₂ =

NADH

0.1 mM

P₁ =

P₂ =

Lactate

0.3 mM

ΔG for these conditions

-14. kJ/M

Note this energy still favors lactate formation even though lactate is hundreds of times higher in concentration in the cell than is pyruvate. This is important since the cell depends on pyruvate to be a good place to dump electrons in an emergency

Mechanism for Chemistry

Mechanism for Enzyme

Hover your mouse over a step to reveal a description

Aldolase. Animation of the Lactate Dehydrogenase reaction The histidine is an amino acid in the active site: "Start" begins an animation of the redox reaction. It proceeds through the reaction in the "forward" direction and then "backwards" again. Note how the enzyme is involved. "+" increases speed while "-" decreases the animation speed. You may also step through the reaction using "next" or "previous"

Compare the animated reaction to the "arrow pushing" scheme at the right. See if you can correlate the electron movement in the animation to the arrows in the static picture above.

Picture of Enzyme with substrate