Fatty acid recycling and degradation

This pathway mainly shows the oxidation of fatty acids. The fatty acid oxidation takes place in mitochondria in animals. This is the reverse of fatty acid biosynthesis and utilises CoA as acyl carrier. The four main enzymes involved in the degradation of fatty acids are acyl-CoA oxidase (acyl-CoA dehydrogenase), Enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-oxoacyl-CoA thiolase. Each cycle of activities of these enzymes removes 2-carbon units in the form of acetyl-CoA. This cycle of activities can continue until the fatty acid chain is degraded to 4-carbon acetoacetyl-CoA. Acetoacetyl-CoA can then be cleaved to 2 acetyl-CoAs by the reverse action of the enzyme acetyl-CoA C-acetyltransferase.

 

This pathway may provide a carbon source in the form of acetyl-CoA for mitochondrial TCA cycle and other biosynthesis pathways. The enzymes acyl-CoA oxidase and 3-hydroxyacyl-CoA dehydrogenase are absent in Plasmodium falciparum.  There is no biochemical evidence of this pathway taking place in P. falciparum and therefore not reconstructed in MPMP.

 

Enzyme EC Number Gene id Protein localisation Localisation data source
Alcohol dehydrogenase 1.1.1.1 TGME49_311780    
Long-chain-3-hydroxyacyl-CoA dehydrogenase 1.1.1.211 TGME49_232090 Mitochondrion Previous publication
3-hydroxyacyl-CoA dehydrogenase 1.1.1.35 TGME49_234570 Apical (anterior vesicle); Cytosol; Posterior vesicle Apiloc
Aldehyde dehydrogenase 1.2.1.3 TGME49_264000    
Aldehyde dehydrogenase 1.2.1.3 TGME49_288450    
Acyl-CoA oxidase 1.3.3.6 TGME49_247500    
Acyl-CoA oxidase 1.3.3.6 TGME49_315480    
Acetyl-CoA C-acyltransferase (3-oxoacyl-CoA thiolase) 2.3.1.16 TGME49_273740    
Acetyl-CoA C-acetyltransferase (acetoacetyl-CoA thiolase) 2.3.1.9 TGME49_301120 Mitochondrion Previous publication
Enoyl-CoA hydratase 4.2.1.17 TGME49_202140    
Enoyl-CoA hydratase 4.2.1.17 TGME49_242390    
Enoyl-CoA hydratase 4.2.1.17 TGME49_310830    
Enoyl-CoA hydratase 4.2.1.17 TGME49_317705    
Long-chain-fatty-acid-CoA-ligase 6.2.1.3

TGME49_243800

Cytosol Previous publication
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 TGME49_247760 Mitochondrion Previous publication
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 TGME49_297220    
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 TGME49_310080 Cytosol Previous publication
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 TGME49_310150 Mitochondrion Previous publication

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
Fatty acid Fatty acid biosynthesis in the apicoplast, Fatty acid elongation in the cytosol, Fatty acid elongation in the ER, Host Acetyl-CoA Fatty acid elongation in the cytosol, Fatty acid elongation in the ER, Fatty acid biosynthesis in the Apicoplast, Tricarboxylic acid (TCA) cycle
    Alcohol ?