Lactate Dehydrogenase: "The Case of the Biochem Killer"

Structure/Function/Importance

Kerri: “OK, so the final is in 6 hours. We got this! We just need to go over some things. So she’s definitely going to ask about structure so what’s the structure again?”

Katelyn: “So LDH is a tetramer and there are five different kinds of LDH made up of a combo of muscle and heart subunits. And LDH has a secondary structure of about 40% alpha helices and 23% beta sheets.”

Ernestine: “OH yeah, and the heart has 4 heart subunits, skeletal muscle has 4 muscle subunits, and the lungs have a mix of 2 heart and 2 muscle subunits.”

Katelyn: “Wait, what’s the difference between the heart and muscle subunits?”

Kerri: “Oh hey, the H subunits are found mainly in the heart muscle LDH, which is more specific for the aerobic oxidation of pyruvate. The M subunits are mainly found in the liver and skeletal muscle because it is geared toward anaerobic respiration and the reduction of pyruvate.”

Pause

(Killer walks by…)

Ernestine: “What was that?”

Katelyn: “What was what?”

Kerri: “You both are imagining things. Anyway, LDH is important because it helps provide energy for the body.”

Ernestine: “So… how does it do that again?”

Katelyn: “Remember, Dr. Cole talked about how the Gibbs Free energy for the reaction LDH catalyzes is about -200kJ/mol, but 93% of that energy remains in the lactate. So, the reverse of this reaction lets your body use that remaining energy in the lactate.”

Ernestine: “Oh yeah, that’s right.”

Kerri: “And don’t forget that LDH has medical uses, because it can be used as diagnostic testing for a bunch of health problems, especially testing for signs of a heart attack or tissue damage.”

Ernestine: “That’s because LDH has different isoenzymes and testing for a higher level of one isozyme over the other, like elevated H-type LDH, is what let’s you know something is wrong. Right?”

Katelyn: “Right.”

Mechanism

Samantha: “I overheard you talking about LDH, but your forgot the mechanism.”

(picks up bloody textbook and walks closer)

Samantha: Samantha begins to explain as Katelyn and Ernestine start running away, keeps explaining calmly as they’re running)
“Lactate is oxidized after NAD+ binds to the enzyme followed by lactate binding to the enzyme. The hybrid ion is then transferred in either direction to yield two ternary complexes-- enzyme-NAD+-lactate and enzyme-NADH-pyruvate.
Pyruvate dissociates from the enzyme, followed by NADH. NADH dissociation is the rate limiting step in the reaction. The reverse reaction involves the coenzyme NADH binding first, followed by the substrate then the pyruvate. The more favorable reaction is the conversion of pyruvate to lactate, with regeneration of NAD+ (Busby, n.d.).

References

Busby., R. (n.d.) Reaction Mechanism for Lactate Dehydrogenase. Retrieved from: http://www.chem.uwec.edu/webpapers_f9...

Lactate Dehydrogenase. (2014). Proteopedia. Retreived from: http://www.proteopedia.org/wiki/index...

Worthington, K. (2015). Lactate Dehydrogenase. Worthington Biochemical Corporation. Retrieved from: http://www.worthington-biochem.com/ld...

Royalty Free Music from Incompetech.com

MacLeod, K. (2015). All this. Incompetech.com [online].

MacLeod, K. (2015). Monkeys spinning monkeys. Incompetech.com [online].

MacLeod, K. (2015). Come play with me. Incompetech.com [online].

MacLeod, K. (2015). Hyperfun. Incompetech.com [online].

Music

Title Credits and End Credits Music: “Come Play With Me”

Classroom Discussion Scene Start Music: “Monkeys Spinning Monkeys”

Biochem Killer Theme Music: “All This”

Blooper Reel Music: “Hyperfun”