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
Alcohol dehydrogenase 1.1.1.1 NCLIV_055560
Long-chain-3-hydroxyacyl-CoA dehydrogenase 1.1.1.211 NCLIV_032080
3-hydroxyacyl-CoA dehydrogenase 1.1.1.35 NCLIV_042220
Aldehyde dehydrogenase 1.2.1.3 NCLIV_024060
Aldehyde dehydrogenase 1.2.1.3 NCLIV_040940
Acyl-CoA oxidase 1.3.3.6 NCLIV_058170
Acyl-CoA oxidase 1.3.3.6 NCLIV_065250
Acetyl-CoA C-acyltransferase 2.3.1.16 NCLIV_033970
Acetyl-CoA C-acetyltransferase 2.3.1.9 NCLIV_069850
Enoyl-CoA hydratase 4.2.1.17 NCLIV_012140
Enoyl-CoA hydratase 4.2.1.17 NCLIV_017550
Enoyl-CoA hydratase 4.2.1.17 NCLIV_022740
Enoyl-CoA hydratase 4.2.1.17 NCLIV_054880
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 NCLIV_006300
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 NCLIV_018500
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 NCLIV_054200
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 NCLIV_054250
Long-chain-fatty-acid-CoA-ligase 6.2.1.3 NCLIV_063970

 

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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 ?