# Biochemistry/Conversion of pyruvate to acetyl CoA

Metabolism, as all other functions in the human body, is not a simple mechanism. Although performed extremely fast, metabolism has many complex steps. For the multiple steps, there are multiple enzymes catalyzing the process. One of the steps of metabolism is taking pyruvate (from glycolysis) and converting it into CO2 and acetyl-CoA (used in the krebs cycle). In order to perform this action, so it will not be a lengthy process, an enzyme is necessary. The enzyme that catalyzes this action is pyruvate dehydrogenase. Aside from being an enzyme catalyzing the complex steps of metabolism, pyruvate dehydrogenase is very complex, too. The pyruvate dehydrogenase is an extremely complex structure made up of several enzymes: E1, E2, and E3. Since it does contain a complex structure, these enzymes are present within the structure multiple times. Overall, pyruvate dyhydrogenase is a dehydrogenase. As most dehydrogenase do, pyruvate dehydrogenase performs it job with the cofactor of NAD+. NAD+ performs its function by converting NAD+ to NADH+H$^+$. This enzyme complex utilizes substrate channelling which means it achieves the reaction void of releasing its substrate into the reaction solution. The enzyme includes cofactors bound to itself, their names are TPP, Lipoate and FAD.

## Regulation

Pyruvate dehydrogenase is negatively regulated by its own product acetyl CoA, ATP, NADH, and fatty acids while it is being positively regulated via AMP, CoA, NAD$^+$, Ca$^{2+}$. It is sensible because presence of much acetyl CoA, ATP,NADH, and fatty acids refers that there is enough energy or energy source so no need to convert pyruvate into acetyl CoA because there is enough energy and for CoA, NAD$^+$, Ca$^{2+}$ it is vice versa.

## Pyruvate dehydrogenase deficiency

As previously stated, pyruvate dehydrogenase is the enzyme in charge of changing pyruvate into acetyl-CoA (acetyl coenzyme A), a necessity to start the Krebs’s cycle. The question at hang is can pyruvate dehydrogenase go wrong? The answer is yes, and although uncommon, pyruvate dehydrogenase deficiency is an example of what occurs when pyruvate dehydrogenase cannot perform its job. The question left unanswered is what pyruvate dehydrogenase deficiency is? Pyruvate dehydrogenase deficiency is a buildup of lactic acid, or lactic acidosis, which can be life-threatening for many. The most common forms of this lactic acid buildup can cause symptoms such as nausea, abnormal heartbeat, and vomiting. Pyruvate dehydrogenase is also characterized by varies neurological problems. The most common issues occurring with neurological abnormalities are slow mental abilities and motor skills such as sitting. Other neurological problems range from having poor coordination to difficulty walking to being intellectually disabled.

## References

Nelson, D. L., Lehninger, A. L., & Cox, M. M. (2008). Lehninger principles of biochemistry.
Diwan, Joyce J. 2007. Pyruvate Dehydrogenous and The Kreb's Cycle. Web. http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/krebs.htm
Pyruvate Dehydrogenous and The Kreb's Cycle. College of Science / Microbiology. Aug. 3, 1999. Web. http://www.science.siu.edu/microbiology/micr425/425Notes/05-PyrKrebs.html
Genetics Home Reference. Pyruvate dehydrogenase deficiency. Nov. 19. 2012. Web. http://ghr.nlm.nih.gov/condition/pyruvate-dehydrogenase-deficiency