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Sources of Fatty acids

  • Diet
  • Adipolysis
  • De novo synthesis(from precursors)- Carbohydrates, protein, and other molecules obtained from diet in excess of the body’s need can be converted to fatty acids, which are stored as triglycerides

De novo fatty Acid Synthesis


  • Fatty acids are synthesized by an extra mitochondrial system
  • This system is present in many tissues, including liver, kidney, brain, lung, mammary gland, and adipose tissue.
  • Acetyl-CoA is the immediate substrate, and free palmitate is the end product.
  • Its cofactor requirements include NADPH, ATP, Mn2+, biotin, and HCO3 (as a source of CO2).

Sources of NADPH

  • NADPH is involved as donor of reducing equivalents
  • The oxidative reactions of the pentose phosphate pathway are the chief source of the hydrogen required for the reductive synthesis of fatty acids.
  • Tissues specializing in active lipogenesis—i.e., liver, adipose tissue, and the lactating mammary gland—possess an active pentose phosphate pathway (Figure-1).

 HMP pathway- major source of NADPH

Figure-1- The reaction 1 and 2 are catalyzed by Glucose-6-P dehydrogenase and 6-phospho gluconate dehydrogenase respectively.

  • Other sources of NADPH include the reaction that converts malate to pyruvate catalyzed by the “Malic enzyme” (NADP malate dehydrogenase) – figure-2 and the extra mitochondrial Isocitrate dehydrogenase reaction (probably not a substantial source, except in ruminants) figure-3.

 Malic enzyme- alternative source of NADPH

Figure-2- It is a reversible reaction, pyruvate produced in the reaction reenters the mitochondrion for further utilization

 Cytosolic dehydrogenase- Alternative source of NADPH

Figure-3-There are three isoenzymes of Isocitrate dehydrogenase. One, which uses NAD+, is found only in mitochondria. The other two use NADP+ and are found in mitochondria and the cytosol. Respiratory chain-linked oxidation of Isocitrate proceeds almost completely through the NAD+-dependent enzyme.

Sources of Acetyl co A

  • Acetyl co A is produced primarily from pyruvate, ketogenic amino acids, fatty acid oxidation and by alcohol metabolism
  • It is a substrate of TCA cycle and a precursor for fatty acids, ketone bodies and sterols.

Enzymes and cofactors involved in the process of Fatty acid synthesis

Two main enzymes-

  • Acetyl co A carboxylase
  • Fatty acid Synthase

Both the enzymes are multienzyme complexes

Coenzymes and cofactors are-

  • Biotin
  • Mn++
  • Mg++

Transportation of Acetyl co A (Figure-4)

  • Fatty acid synthesis requires considerable amounts of acetyl-CoA
  • Nearly all acetyl-CoA used in fatty acid synthesis is formed in mitochondria
  •  Acetyl co A has to move out from the mitochondria to the cytosol
  • Acetate is shuttled out of mitochondria as citrate
  • The mitochondrial inner membrane is impermeable to acetyl-CoA
  • Intra-mitochondrial acetyl-CoA first reacts with oxaloacetate to form citrate, in the TCA cycle catalyzed by citrate synthase
  • Citrate then passes into the cytosol through the mitochondrial inner membrane on the citrate transporter.
  • In the cytosol, citrate is cleaved by citrate lyase regenerating acetyl-CoA.

 Export of Acetyl co A

Figure-4- Transportation of acetyl co A out of the mitochondria through citrate transporter

Fate of Oxalo acetate (Figure-5)

The other product of Citrate cleavage, oxaloacetate can be-

  • Channeled towards glucose production
  • Converted to malate by malate dehydrogenase
  • Converted to Pyruvate by Malic enzyme, producing more NADPH, that can be used for fatty acid synthesis
  • Pyruvate and Malate pass through special transporters present in the inner mitochondrial membrane

 Fate of oxalo acetate

Figure-5- Fate of Oxalo acetate

To be continued …..


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