Term
| Pyruvate Dehydrogenase activity is found in which part of the cell? |
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Definition
| mitochondria, specifically in the mitrochondrial matrix |
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Term
| What is the function of Pyruvate Dehydrogenase? |
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Definition
Pyruvate -> Acetyl Coa
Pyruvate Dehydrogenase catalyzes oxidative decarboxylation in the above reaction |
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Term
| Pyruvate Dehydrogenase is a complex containing how many distinct enzymes? |
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Definition
Many copies of 3 enzymes
E1, E2, E3 |
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Term
| What is the enzyme and prosthetic group associated with E1 of Pyruvate Dehydrogenase? |
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Definition
Pyruvate Dehydrogenase
Prosthetic Group: Thiamine pyrophosphate TPP |
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Term
| What is the enzyme and associated prosthetic group of E2 of Pyruvate Dehydrogenase? |
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Definition
Dihydrolipoyl Transacetylase
Prosthetic group: Lipoamide |
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Term
| What is the enzyme and prosthetic group related to E3 of Pyruvate Dehydrogenase? |
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Definition
Dihydrolipoyl Dehydrogenase
Prosthetic Group: FAD |
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Term
| What are diseases associated with Thiamine deficiency? |
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Definition
Beriberi: dry, wet, and infantile
Wernicke-Korsakoff syndrome: Thiamine important cofactor for Transketolase in PPP |
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Term
| What compounds directly inhibit the action of Pyruvate Dehydrogenase? |
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Definition
NADH and Acetyl CoA
NADH by competing with NAD for E3
Acetyl CoA by competing with CoA for E2 |
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Term
| What enzymes activate/deactivate Pyruvate Dehydrogenase? |
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Definition
Pyruvate Dehydrogenase is activated by Pyruvate Dehydrogenase Phosphatase
inhibited by Pyruvate Dehydrogenase Kinase |
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Term
| What compounds upregulate the action of Pyruvate Dehydrogenase Kinase? |
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Definition
| ATP, Acetyl CoA, and NADH |
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Term
| What compounds inhibit Pyruvate Dehydrogenase Kinase action? |
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Definition
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Term
| What role does calcium, in muscles, play on the action of Pyruvate Dehydrogenase? |
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Definition
| Calcium can upregulate a calcium sensitive isomer of Pyruvate Dehydrogenase Phosphatase which then upregulates the action of Pyruvate Dehydrogenase (by dephosphorylating it) |
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Term
| What happens with Pyruvate Dehydrogenase during starvation? |
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Definition
In select tissues Pyruvate Dehydrogenase is inhibited by increaseing of Pyruvate Dehydrogenase Kinase and decreasing of Pyruvate Dehydrogenase Phosphatase.
This is a special compensatory mechanism that allows for preferential glucose uptake in the tissues that critically need them (brain, aerobic tissue) |
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Term
| Recent studies link Pyruvate Dehydrogenase Kinase activity with which two pathologies? |
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Definition
| Cancer and Pulmonary Hypertension |
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Term
| By what mechanism does arsenic inhibit Pyruvate Dehydrogenase? |
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Definition
arsenic is a strong inhibitor of lipoamide containing enzymes
remember that E2 (dihydrolipolyl transacetolase) enzyme of Pyruvate dehydrogenase uses lipamide as a prosthetic group
finally the clinical presentation mimics that of thiamine deficiency as arsenic inhibits the enzymes that use thiamine |
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Term
| What are common pathways to arsenic exposure? |
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Definition
| poultry, industries that use inorganic arsenic, occupational exposure (coper/lead smelting, wood treatment), found in some wines, contaminated well water |
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Term
| How does one diagnose and treat arsenic poisoning? |
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Definition
arsenic can be measured in the blood, hair, urine, or fingernails.
Treatment is chelation |
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Term
| What is the clinical picture of Pyruvate Dehydrogenase Deficiency? |
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Definition
Congenital lactic acidosis. This can cause neonatal death or brain damage.
Ingestion of a carbohydrate rich diet can cause episodic ataxia |
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Term
| What is the the therapy for pyruvate dehydrogenase deficiency? |
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Definition
| Low carb (ketogenic) diet to try and maintain low pyruvate levels |
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