Pantothenate and CoA biosynthesis

Curator(s): Erin Kinney

Panthothenate (vitamin B5) is the precursor of coenzyme A and is the prosthetic group of acyl carrier protein (ACP). Its name is derived from the Greek pantothen meaning “from everywhere” and small quantities of pantothenic acid are found in nearly every foodstuff. Coenzyme A (CoA) may act as an acyl group carrier to form acetyl-CoA and other related compounds and is used as a way to transport carbon atoms within the cell. CoA is important in energy metabolism for pyruvate to enter TCA cycle as acetyl-CoA, and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle. CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine. About 85% of dietary pantothenic acid is as CoA or phosphopentetheine. In the intestinal lumen, these undergo hydrolysis to phosphopantetheine, then pantetheine. Intestinal mucosal cells have high pantetheinase activity and rapidly hydrolyze pantetheine to yield free pantothenic acid. Coenzyme A is synthesized in a five-step process from pantothenate. First, antothenate (Vitamin B5) is phosphorylated to 4’-phosphopantothenate by the enzyme pantothenate kinase, next a cysteine is added to 4’-phosphopantothenate by the enzyme phosphopantothenoylcysteine synthetase to form 4’-phospho-N-pantothenoylcysteine (PPC). In the next step, PPC is decarboxylated to 4’-phosphopantetheine by phosphopantothenoylcysteine decarboxylase. In the fourth step,4’-phosphopantetheine is adenylylated to form dephospho-CoA by the enzyme phosphopantetheine adenylyl transferase. Finally, dephospho-CoA is phosphorylated using ATP to coenzyme A by the enzyme dephosphocoenzyme A kinase. CoA undergoes dephosphorylation, catalyzed by lysosomal acid phosphatasae to dephospho-CoA, followed by pyrophosphatase action to release 4’-phosphotantetheine and 5’AMP. Red blood cells contain pantothenic acid, pantetheine 4’-phosophate and pantetheine.[PATHMAN]    
Zoom out 50% Move left to zoom out, right to zoom in Zoom in 50% 100%

Pantothenate and CoA biosynthesis node1 2 Pyruvate Pyruvate->node1 Pyruvate node2 Pyruvate->node2 node3 2-Acteolactate node2->node3 Glycolysis Glycolysis->Pyruvate node4 node3->node4 node5 2,3 -Dihydroxy -3-methylbutanoate node4->node5 node6 node5->node6 node7 3-Methyl -2-oxobutanoate node6->node7 node11 node7->node11 node8 node8->node7 node10 L-Valine node8->node10 node9 node9->node7 node9->node10 node12 2-Dehydropantoate node11->node12 node13 node12->node13 node14 (R)-Pantoate node13->node14 node20 node14->node20 node21 node14->node21 node54 node14->node54 node15 node15->node7 node16 (R) -3,3 -Dimethylmalate node15->node16 node17 node17->node16 node19 (R) -4 -Dehydropantoate node17->node19 node18 node18->node14 node18->node19 node22 (R)-Pantothenate node20->node22 node21->node22 node23 node22->node23 node24 D-4' -Phospopantothenate node23->node24 node27 (R) -4' -Phospho-pantothenoyl -L-cysteine node23->node27 node31 4'-Phosopho -pantetheine node23->node31 node26 node24->node26 node25 L-Cysteine node25->node26 Cysteine and Methionine Metabolism Cysteine and Methionine Metabolism->node25 node26->node27 node58 node27->node58 node28 N-Pantothenoyl -cysteine node28->node23 node29 node28->node29 Pantetheine node29->Pantetheine Pantetheine->node23 node30 Pantetheine->node30 node32 Pantetheine->node32 node30->node31 node32->node22 Pantothenol Pantothenol->node22 node33 B-Alanine metabolism node33->node22 node34 node34->node31 node36 Dephospho-CoA node34->node36 node35 node35->node31 node35->node36 node37 node36->node37 node38 Coenzyme (CoA) node37->node38 node41 node38->node41 node57 2.7.8.- node38->node57 node39 node39->node31 node42 Apo-[acp] node39->node42 node40 Acyl-carrier protein node40->node39 node41->node40 node43 Adenosine 3',5'-bisphosphate node41->node43 node42->node41 node42->node57 node44 B-Alanine node44->node20 node44->node21 Propanoate metabolism Propanoate metabolism->node44 node45 node45->node44 node46 L-Aspartate node46->node45 node47 Alanine, aspartate and glutamate metabolism node47->node46 node48 node48->node44 node49 N-Carbamoyl -B-alanine node49->node48 node50 node50->node49 node51 5,6 -Dihydro -uracil node51->node50 node52 node52->node51 Uracil node52->Uracil node53 node53->node51 node53->Uracil node55 (R) -4 -Phosphopantoate node54->node55 node56 node55->node56 node56->node24 node57->node40 node57->node43 node58->node31 print "