BIOLCHEM 415 1st Edition Lecture 18 Outline of Last Lecture I. Different pathways are used for the synthesis and degradation of important macromoleculesII. UTP is important in glycogen synthesis III. Regulation is important to keep glycogen synthesis goingOutline of Current Lecture IV. Introduction to the Pyruvate Dehydrogenase (PDH) complexCurrent LectureThe Citric Acid Cycle picks up where glycolysis endsPDH complex converts pyruvate to Acetyl CoA- acetyl CoA is what “starts” the citric acid cycle- functions in the matrix of the mitochondrionPDH complex- 3 enzymes and 5 coenzymesCoenzyme A- carrier of acyl groups and derived from vitamin B5- reactive –SH group is involved in the reactions- forms a high energy thioester bondFlavin Adenine Dinucleotide- FAD, electron carrier, B2NAD+These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- electron carrier, B3- nicotinamide ring can be reduced (active site)Lipoic Acid- facilitates acyl transfer reactions- long chain with reactive disulfide bond- amide linkage at –OH bond at the end of the chain- lipoamide transfers intermediates to active sitesThiamine Pyrophosphate (TPP)- aldehyde transfers, B1- a reactive carbanion can be formed on the thiazole ringPDH complex- at core are E2 dihydrolipoyl transacetylase subunits- works as a catalytic cycle- a cycle of FAD TPP- decarboxylation of pyruvate- catalyzed by E1 Pyruvate Dehydrogenases- carbanion (formed from TPP) attacks carbonyl carbon of pyruvate- addition compound decarboxylates (CO2 and hydroxyethyl TPP)- resonance forms of hydroxyethyl TPP can be protonated- oxidation of hydroxyethyl intermediate- carbanion of hydroxyethyl attacks sulfur in lipoamide (disulfide reduced)- hydroxyethyl transferred to acetyl group- acetyllipoamide- formation of acetyl CoA- done by E2 dihydrolipoyl Transacetylase- sulfhydryl group of CoA attacks carbonyl carbon of acetyl group- acetyl group transferred to CoA - produced acetyl CoA and dihydrolipoamide- Acetyl CoA enters the Citric Acid Cycle- dihydrolipoamide is recycled back into lipoamide- by E3 dihydrolipoyl dehydrogenase - NADH and FAD are yielded- net reaction- pyruvate + CoA + NAD+ Acetyl CoA + CO2 + NADH + H+Acetyl CoA- formation commits the dehydration of glucose- inhibits E2 dihyrolipoyl transacetylase subnunits- NADH inhibits E3 dihydrolipoyl dehydrogenase subunitsCovalent Modificatioin- key regulation of pyruvate dehydrogenase- PDH kinase associates with E2- ADP and pyruvate inhibit kinase- Ca2+ stimulates phosphataseCellular energy charge regulates PDH complex- high energy charge (ATP high)- inhibits E2 and E3- PDH kinase stimulated- low energy charge (ADP high)- kinase inhibited - phosphatase stimulatedThiamine deficiency- beriberi- cardiovascular and neurological disorder arises from thiamine deficiency- nervous system uses glucose as fuel source- cannot metabolize fats- rice and legumes can be used to supplement thiamine into dietArsenite and Merucry- inhibit
View Full Document
Unlocking...