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Course: MCAT > Unit 2

Lesson 1: Foundation 1: Biomolecules

Metabolism: Acetyl-CoA and fatty acid synthesis

Problem

We generally associate glycolysis with its main function: to convert glucose to pyruvate, which is transported into mitochondria and converted to acetyl-CoA, feeding the citric acid cycle. However, the acetyl-CoA created from pyruvate inside the mitochondria can be also converted to citrate molecules, shuttled back to the cytosol, and reconverted to acetyl-CoA, where it is used to synthesize fatty acids such as palmitate (shown in Figure 1).
Figure 1 Palmitate (C16H32O2)
The synthesis of palmitate occurs in the cytosol according to the two-part reaction formula shown in Equations 1 and 2.
7 acetyl-CoA + 7 CO2 + 7 ATP → 7 malonyl-CoA + 7 ADP + 7 Pi
Equation 1
Acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14H+ → palmitate + 7 CO2 + 8 CoA + 14 NADP+ + 6H2O
Equation 2
The conversion of acetyl-CoA to malonyl-CoA is catalyzed by the enzyme acetyl-CoA carboxylase, whereas the conversion of citrate to acetyl-CoA in the cytosol is catalyzed by the enzyme citrate lyase according to Equation 3.
citrate + ATP + CoA + H2O → oxaloacetate + acetyl-CoA + ADP + Pi
Equation 3
Both citrate lyase and acetyl-CoA carboxylase are subject to multiple types of enzymatic regulation. For instance, acetyl-CoA carboxylase is activated by citrate. This type of enzymatic regulation is commonly called a feedforward loop.
Where is citrate produced?
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