Why are beta-keto acids easier to decarboxylate that alpha-keto acids?
Beta-keto acids are resonance stabilized. Alpha-keto acids form an unstable carbanion.
Is pyruvate easy or difficult to decarboxylate?
Difficult it is an alpha-keto acid.
Pyruvate Decarboxylation Reaction
Done by pyruvate dehydrogenase complex. Vitamins are key coenzymes in carrying out this reaction.
Alcoholics and people with eating disorders cannot walk very well. What biochemical molecule is deficient and causes these symptoms?
Thiamine. It can cause polyneuropathy, paresthesia and paresis (partial paralysis) through nerve demyelination
What are the 5 P's of thiamine deficiency?
Polyneuropathy, Paresthesia, Paresis, Psychiatric, Possible Edema
What makes thiamine so reactive?
Center carbon atom can be extracted to form a carbanion.
Why is thiamine a good coenzyme for decarboxylation of pyruvate?
Its attack on pyruvate's ketone resembles a beta-keto acid which is easier to decarboxylate.
What portion of the pyruvate dehydrogenase complex would be lost in a patient with thiamine deficiency?
The E2 core.
alpha-keto acid dehydrogenase reaction sequences.
How does arsenic cause harm?
It blocks reoxidation of a disulfide group in pyruvate dehydrogenase complexes.
How is pyruvate made from acetyl-CoA?
It isn't. It is an irreversible reaction in humans.
How is pyruvate dehydrogenase complex regulated?
E1 kinase phosphorylates complex and inactivates it. E1 phosphatase removes phosphate group and activates the complex. E1 kinase is inhibited by ADP and pyruvate. E1 phosphatase is stimulated by Ca.
What substances change pyruvate dehydrogenase complex conformation so it is more readily phosphorylated by E1 kinase?
Acetyl CoA and NADH.
What substances change pyruvate dehydrogenase complex conformation so it is more readily dephosphorylated by E1 phosphatase?
Pyruvate and NAD.
A parent brings her 2 year old in complaining of weakness, seizures, vomiting and opthalmoplegia. What syndrome might this child be suffering from? What could you give the patient to alleviate symptoms?
Leigh syndrome. Giving high levels of thiamine can compensate for malfunction in pyruvate dehydrogenase and decrease lactic acid levels in the blood.