Lipid and Amino Acid Metabolism for the MCAT: Everything You Need to Know
/Learn key MCAT concepts about lipid and amino acid metabolism, plus practice questions and answers
(Note: This guide is part of our MCAT Biochemistry series.)
Part 1: Introduction
Part 2: Fatty acid synthesis
a) The citrate shuttle
b) The oxaloacetate shuttle
c) Palmitic acid synthesis
Part 3: Beta oxidation
a) Lipid absorption
b) Activation
c) Oxidation of saturated fatty acids
d) Unsaturated fatty acid metabolism
e) Ketogenesis
Part 4: Amino acid metabolism
a) Protein absorption
b) Protein catabolism
c) Urea cycle
Part 5: Metabolic overview and high-yield terms
Part 6: Passage-based questions and answers
Part 7: Standalone questions and answers
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Part 1: Introduction
Whether you are running a marathon or sleeping in on a Sunday morning, your body is carrying out a plethora of chemical reactions. These reactions all contribute to maintaining homeostasis and using energy. While you may already be familiar with carbohydrate metabolism, your body, the ever-so versatile machine, has additional metabolic pathways to acquire and store energy.
While the MCAT will only rarely test you on details of each metabolic pathway, you will need to understand the big picture behind metabolism by identifying patterns and making connections. Knowing the underlying rationale behind the topics you review is what will ultimately allow you to demonstrate mastery on test day. Make sure to complement your studying with extensive practice, including the practice passage and questions we’ve included at the end of this guide.
Let’s get started!
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Part 2: Fatty acid synthesis
Fatty acids are long hydrocarbon chains that serve as great sources of energy for the body. The only fatty acid that the human body can synthesize by itself is palmitic acid, a 16-carbon fatty acid.
Figure: Palmitic acid is a 16-carbon long fatty acid.
Its synthesis occurs primarily in the cytoplasm of hepatocytes and follows the net reaction:
7 ATP + 8 Acetyl-CoA + 14 NADPH → Palmitic Acid + 7 ADP + 7 Pi + 8 CoA + 14 NADP⁺ + 6H₂O
The synthesis of palmitic acid is fairly lengthy and is composed of several different components. We’ll walk through each of the stages of this synthesis that you will need to know for the MCAT.
a) The citrate shuttle
After the consumption of excess carbohydrates, acetyl-CoA begins to accumulate in the mitochondrial matrix. Recall that glycolysis produces pyruvate, which is converted into acetyl-CoA via the pyruvate dehydrogenase complex. Citrate synthase then catalyzes the formation of citrate from acetyl-CoA and oxaloacetate.
Typically, this is how acetyl-CoA enters the tricarboxylic acid cycle (TCA). However, since an excess of carbohydrates has been consumed, regulatory measures are taken to slow the TCA cycle, and citrate begins to accumulate. Recall that the TCA cycle’s rate-limiting step is isocitrate dehydrogenase, which acts downstream of citrate synthase—hence causing a build-up of citrate.
To remedy this, citrate is shuttled to the cytoplasm via a citrate shuttle. An enzyme in the cytoplasm catalyzes the reverse reaction of citrate synthase, by splitting citrate into acetyl-CoA and oxaloacetate.
Figure: An overview of the citrate shuttle.
b) The oxaloacetate shuttle
The oxaloacetate that is now present in the cytoplasm then re-enters the mitochondrial matrix in a series of steps:
Oxaloacetate is converted to malate.
Malic enzyme catalyzes the conversion of malate into pyruvate and produces NADPH as a byproduct. This NADPH will be critical in later steps of synthesis.
Pyruvate enters the mitochondrion and is converted into oxaloacetate by pyruvate carboxylase.
Here, oxaloacetate can again be paired with acetyl-CoA to form citrate via citrate synthase.
Why go through the trouble of shuttling citrate and pyruvate back and forth? Note that the oxaloacetate shuttle results in the production of NADPH. This NADPH is a crucial electron carrier that will be needed later in the synthesis. Without the oxaloacetate shuttle, these electrons would not be able to move from the inner mitochondrial membrane into the cytoplasm.
c) Palmitic acid synthesis
In the cytoplasm, acetyl-CoA is converted into malonyl-CoA via the addition of a carbon dioxide molecule. This reaction is catalyzed by acetyl-CoA carboxylase, the rate-limiting step of fatty acid synthesis. Finally, fatty acid synthase, a multienzyme complex, catalyzes the polymerization of palmitic acid. This requires NADPH and produces NADP⁺, carbon dioxide, and water as byproducts.
Figure: Synthesis of palmitic acid.
Note that the synthesis of fatty acids does not require the presence of any precursor or template molecules. This is in contrast to the synthesis of DNA or RNA, which requires the presence of a template molecule to form “copies” of itself.
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