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How Does Pyruvate Dehydrogenase

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Pyruvate dehydrogenase is a large and complex molecule with interesting structural, catalytic and regulatory properties. It is the first component enzyme of pyruvate dehydrogenase complex (PDC). The pyruvate dehydrogenase complex contributes to transforming pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, so pyruvate dehydrogenase contributes to linking the glycolysis metabolic pathway to the citric acid cycle and releasing energy via NADH.
The oxidation of pyruvate occurs in the mitochondria of the cell. The mitochondria is an organelle in the cell. It is considered the "powerhouse" of the cell. Pyruvate is transported there via pyruvate …show more content…

However this is not as simple as it looks and the whole thing is actually a five step process. Step 1: Pyruvate is decarboxylated by pyruvate dehydrogenase with help from TPP. Step 2: The reactive carbon of the TPP is oxidized and transferred as the acetyl group to lipoamide. This forms hydroxyethyl-TPP. An H+ ion is required for the intermediate to give off CO2. Step 3: E2 (Dihydrolipoyl transacetylase with cofactor lipoamide) oxidizes hydroxyethyl- to acetyl- and then transfers acetyl- to CoA, forming acetyl-CoA. Step 4: Acetyl CoA was made in the previous step. However, the process is incomplete. The E2 is still attached to the acetyl CoA molecule. So, E3 (Dihydrolipoyl dehydrogenase) oxidizes the thiol groups of the dihydrolipoamide back to lipoamide. Step 5: As a side reaction, NAD+ becomes reduced to NADH.
Pyruvate dehydrogenase complex deficiency (PDCD) is a rare disorder of carbohydrate metabolism caused by a deficiency of one of the three enzymes in the pyruvate dehydrogenase complex (PDC). The age of onset and severity of disease depends on the activity level of the PDC enzymes. Individuals with PDCD beginning prenatally or in infancy usually die in early childhood. Those who develop PDCD later in childhood may have mental retardation and other neurological symptoms and usually survive into …show more content…

These mutations lead to a shortage of E1 alpha protein or result in an abnormal protein that cannot function properly. A decrease in functional E1 alpha leads to reduced activity of the pyruvate dehydrogenase complex. Other components of the pyruvate dehydrogenase complex are also involved in pyruvate dehydrogenase deficiency. Although it is unclear how mutations in each of these genes affect the complex, reduced functioning of one component of the complex appears to impair the activity of the whole

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