The four main classes of biological macromolecules are proteins, carbohydrates, nucleic acids, and:
lipids.
Lipids are a class of water-insoluble organic molecules that includes triglycerides, cholesterol, waxes, and more.
Name three roles that lipids play in the human body.
Lipids play a variety of roles, including:
- maintaining cell structure (via lipid-based membranes)
- participating in biological signaling, and
- serving as energy storage molecules.
Most fat stored in the human body, as well as the majority of dietary fat, exists in the form of:
triglycerides.
Triglycerides, or triacylglycerols, are molecules consisting of a glycerol backbone and three fatty acids.
In a triglyceride, each fatty acid is attached to the glycerol backbone via which functional group?
An ester
As such, triglycerides contain three ester linkages: one for each fatty acid chain on the molecule.
The hydrolysis of a triglyceride using a strong base (such as NaOH) is termed:
saponification.
Saponification gets its name from “soap-making,” due to the soaplike nature of the products. (In fact, the process is sometimes actually used to make soap.)
Name the products of a complete saponification reaction in which NaOH was used.
The products of saponification are glycerol and three fatty acid salts.
These are “salts” (here, deprotonated fatty acids associated with sodium atoms) rather than actual fatty acids because saponification utilizes a strong base (here, NaOH), which causes the products to be deprotonated. However, if acid is added in a later step, these salts will be protonated to form fatty acids.
How many molecules of NaOH are required to completely saponify an unsaturated triglyceride?
Three molecules
Since all triglycerides contain three fatty acid tails, complete saponification always requires three units of NaOH: one for each tail. (The fact that this triglyceride is unsaturated is actually irrelevant to the correct answer.)
True or false:
Saponification involves the breakage of ester linkages.
True
In a triglyceride, the three fatty acid tails are attached to the glycerol backbone via ester linkages. These bonds are broken during saponification.
________ fatty acids are those that contain no carbon-carbon double bonds in their fatty acid chains. In these fatty acids, all carbons except the carbonyl carbon are bound to ________ other atoms.
Saturated fatty acids are those that contain no carbon-carbon double bonds in their fatty acid chains. In these fatty acids, all carbons except the carbonyl carbon are bound to four other atoms.
________ fatty acids are those that contain at least one carbon-carbon double bond in their fatty acid chains. In these fatty acids, at least one carbon in the chain is bound to only ________ other atoms.
Unsaturated fatty acids are those that contain at least one carbon-carbon double bond in their fatty acid chains. In these fatty acids, at least one carbon in the chain is bound to only three other atoms.
Since carbon is saturated when it is attached to four other atoms (via single bonds), it is considered unsaturated when attached to fewer than four atoms.
Which has a higher melting point: a typical saturated fat or a typical unsaturated fat?
Saturated fat typically has a higher melting point.
Saturated fats (composed of saturated fatty acids) can stack well due to their lack of “kinks” caused by double bonds. In contrast, unsaturated fats have double-bond kinks, weakening their stacking. As such, saturated fats are more difficult to melt (meaning that they have higher melting points) than unsaturated fats.
A free fatty acid at physiological pH would be most likely to carry what charge (if any)?
A negative charge
Free fatty acids are composed of a nonpolar hydrocarbon tail (uncharged) and a carboxylic acid group. At physiological pH, carboxylic acid groups tend to be negatively-charged (COO−).
Glycerol, which forms the backbone of a triglyceride, is a molecule that contains three -OH groups. What name is given to such molecules?
Triols
Triols are molecules that contain three hydroxyl (-OH) groups. (In contrast, diols are molecules that contain two -OH groups.)
Define:
amphipathic
Amphipathic molecules are those that possess both polar and nonpolar properties.
Fatty acids, which contain a polar (hydrophilic) head and a nonpolar (hydrophobic) tail, exemplify amphipathic compounds.
Fatty acids are often named using “lipid numbers,” where they are designated in the form of C:D.
In this system, C represents the number of ________, and D represents the number of ________.
C represents the number of carbons, and D represents the number of double bonds.
For instance, oleic acid contains 18 carbons and 1 double bond, so its lipid-number nomenclature is 18:1.
When described in lipid-number format, all saturated fatty acids have what number after the colon?
0
In lipid-number format, the number before the colon refers to the number of carbons (which varies), while the number after the colon denotes the number of double bonds in the chain (which is 0 for all saturated fatty acids).
Fatty acids that contain fewer than six carbon atoms are termed:
short-chain fatty acids.
These are the shortest (smallest) fatty acid molecules.
Medium-chain fatty acids are those that contain between ________ and ________ carbon atoms.
Medium-chain fatty acids (FAs) are those that contain between six and 12 carbon atoms.
Medium-chain FAs are longer than short-chain FAs (<6 carbons) but shorter than long-chain FAs (13-21 carbons).
Stearic acid, a saturated fatty acid, has a chemical formula of C18H36O2. With regard to chain length, how is stearic acid classified?
Stearic acid is a long-chain fatty acid.
Long-chain fatty acids are those that contain between 13 and 21 carbon atoms.
Melissic acid, a saturated fatty acid, has a chemical formula of C30H60O2. With regard to chain length, how is melissic acid classified?
Melissic acid is a very long-chain fatty acid.
Very long-chain fatty acids are those that contain more than 21 carbon atoms.
In a fatty acid chain, a certain carbon atom is bound to three hydrogen atoms. This carbon atom is denoted with which Greek letter?
Omega (ω)
The only carbon atom in a fatty acid chain that is attached to three hydrogen atoms is the terminal (end) carbon. This carbon is designated as the omega (ω) carbon, since omega is the last letter in the Greek alphabet.
In a form of fatty acid notation termed delta-x notation, linoleic acid is described as cis-Δ9, cis-Δ12 octadecadienoic acid. What do the delta (Δ) symbols represent in this notation?
Double bonds
This should be answerable even if you aren’t familiar with delta notation, as the delta symbols are preceded by “cis,” which in this context is used to designate double bonds in which the carbon substituents fall on the same side of the double bond.
Name the structure shown below.
This structure is cholesterol.
Cholesterol, a lipid and the precursor to steroid hormones, is recognizable from its structure containing four fused rings.
Cholesterol is found in the cell membranes of which of the following?
Choose from eukaryotic cells, prokaryotic cells, or viruses.
Cholesterol is found in the cell membranes of eukaryotic cells only.
Make sure you understand that the membranes of prokaryotic cells (bacteria) do not contain cholesterol! The AAMC has been known to ask questions about this in their practice materials.
Viruses do not have cell membranes at all, so that option can be easily eliminated.
Name the class of lipid molecules that serves as the primary lipid component of cell membranes.
Phospholipids
A phospholipid is a lipid molecule that contains a phosphate group. Phospholipids are the main component of cell membranes, which exist as lipid bilayers with the polar phospholipid heads pointing outward and the nonpolar tails facing inward.
Describe the structure of a phospholipid.
Phospholipids contain a phosphate group attached to at least one (usually two) fatty acid tails via a backbone.
Most commonly, that backbone is glycerol, a three-carbon alcohol.
Additionally, phospholipids may be modified via the addition of various molecules to the phosphate head group.
Esters consisting of both long-chain alcohols and long-chain fatty acids are lipids termed:
waxes.
Waxes are very large molecules (the alcohol chains alone are typically between 12 and 32 carbon atoms long). Plants and animals (such as honeybees) secrete waxes for various reasons, usually related to their hydrophobic nature.
What is the name of the molecule shown below?
Isoprene
Isoprene is a hydrocarbon compound with the chemical formula C5H8. Terpenes, which are highly biologically important lipids, have structures that consist of repeating isoprene units.
Define:
terpenes
Terpenes are strong-smelling hydrocarbon lipids that are composed of repeating units of isoprene.
While terpenes serve a variety of functions in plants as well as animals, for the MCAT, it is most important that you be able to recognize their isoprene-based structure.
The smallest and simplest terpenes are termed monoterpenes. How many isoprene units comprise a monoterpene?
Two isoprene units
This can be remembered because one isoprene unit wouldn’t be a terpene at all; it would just be isoprene.
Since isoprene has a chemical formula of C5H8, monoterpenes have chemical formulae of C10H16.
A diterpene would be expected to contain how many carbon atoms?
20
As its name indicates, a diterpene is essentially twice the size (and formula) of a monoterpene. Monoterpenes have 10 carbon atoms, so diterpenes would be expected to have 20.
Name the triterpene that serves as a precursor to all steroid hormones (as well as to cholesterol itself).
Squalene
We often remember that cholesterol is the precursor to steroid hormones, but we may not realize that cholesterol itself has a precursor! That precursor is squalene, a triterpene. Like all terpenes, squalene has abundant double bonds, which allow it to easily act as a reactant in various reactions.
Which of the following hormones is derived from squalene?
- Oxytocin
- Estrogen
- Antidiuretic hormone
Estrogen
All steroid hormones are derived from squalene (more specifically, they are derived from cholesterol, which is derived from squalene). Estrogen is the only steroid hormone listed.
Which of the following hormones is NOT derived from squalene?
- Cortisol
- Aldosterone
- Melatonin
Melatonin
This question is essentially asking “which of the following is not a steroid hormone?” Melatonin is an amino acid-derived hormone, not a steroid.
Even if you didn’t know that (although you should!), you can recall that all MCAT-relevant steroid hormones end in “-ol,” “-one,” or “-en.” Melatonin ends in “-in,” so it can’t be a steroid.
Terpenes that have been chemically modified, often in a way that makes them oxygen-containing, can be termed:
terpenoids.
While the terms “terpene” and “terpenoid” have been increasingly used interchangeably in scientific and informal literature, you should understand the distinction on the front of this card for the MCAT.
Name the class of lipids in which the molecule below is categorized.
This molecule is a prostaglandin.
Prostaglandins are lipids that contain exactly 20 carbon atoms. Their structures always include a five-membered ring. Although that alone is enough to answer this question, note that they also are carboxylic acids and always contain carbon-carbon double bonds.
Prostaglandins are derived from which fatty acid?
Arachidonic acid
While you don’t need to be familiar with the structure of this unsaturated fatty acid for the MCAT, you should understand its relationship to prostaglandins, and you may see it referenced in a passage.
Name the fat-soluble vitamins.
The fat-soluble vitamins are vitamins A, D, E, and K.
All other vitamins are water-soluble.
Name the process that facilitates lipid digestion in the small intestine.
Hint: This process is assisted by the presence of bile, the amphipathic nature of which allows fatty acids to be mixed with water and spread apart.
Emulsification
While emulsification is not digestion per se, it facilitates digestion by spreading apart larger clumps of dietary fat. This is accomplished by bile, a substance produced in the liver and stored in the gall bladder.
Name the main enzyme that catalyzes the digestion of fats in the small intestine.
Pancreatic lipase
As its name implies, lipase catalyzes the breakdown of lipids (fats).
If you chose bile instead, note that bile is not an enzyme! Bile simply emulsifies (spreads out) fats to allow the water-soluble pancreatic lipase to access them.
What spherical/cluster-like structures form in the lumen of the small intestine and carry lipids to brush border cells for absorption?
Micelles
Micelles are spherical, amphipathic structures in which fats are carried from the interior (lumen) of the small intestine to the brush borders of small intestinal cells.
Is the interior of a micelle hydrophobic or hydrophilic?
Hydrophobic
As we’ve seen with globular proteins, micelles form based on hydrophobic effects. This means that hydrophobic (nonpolar) portions cluster in the structure’s interior, while hydrophilic (polar) portions face the aqueous environment.
A micelle reaches the brush border, is broken down into its component lipids, and is absorbed into the mucosa. What happens next?
The components are re-esterified.
In other words, the lipids (which had previously been broken down into fundamental components such as fatty acids) are reacted to re-form triglycerides and cholesteryl esters.
Re-esterified lipid components in the intestinal mucosa are then packaged into what structures?
Chylomicrons
Chylomicrons are lipoprotein particles that transport lipids from the intestines to other areas throughout the body.
Name four types of molecules that are found in chylomicrons.
- Triglycerides
- Phospholipids
- Cholesterol
- Proteins
The first three of these molecules are dietary lipids (with triglycerides comprising the bulk of dietary lipids), so it should be logical that they would be found in chylomicrons. Chylomicrons are lipoproteins, so proteins should also make sense on this list.
Lymphatic vessels found within intestinal villi are called:
lacteals.
Lacteals are the small lymphatic vessels that chylomicrons travel through to move away from the intestine and toward the thoracic duct.
Chylomicrons exit the lymphatic system via the thoracic duct, which is a lymphatic vessel that empties into the ________ system.
circulatory
Specifically, the thoracic duct drains into the left subclavian vein, but as the MCAT isn’t an anatomy exam, you’re unlikely to be asked for that detail in particular.
Beta-oxidation is the process of ________, or breakdown, of fatty acids.
Choose from either “catabolism” or “anabolism.”
Beta-oxidation is the process of catabolism, or breakdown, of fatty acids.
An easy way to remember that catabolism refers to breakdown is to note the similarity of its opposite, anabolism, to “anabolic steroids.” Anabolic steroids are meant to build up mass, so anabolism must refer to the buildup of larger macromolecules, while catabolism refers to their breakdown.
In eukaryotes, most beta-oxidation occurs in which organelle?
The mitochondria
Note that in addition to mitochondrial beta-oxidation, a small amount of beta-oxidation (mainly of very long-chain fatty acids) does occur in peroxisomes.
In prokaryotes, where does beta-oxidation occur?
In the cytosol
Prokaryotes lack membrane-bound organelles, so they have neither mitochondria nor peroxisomes (the two organelles in which beta-oxidation occurs in eukyarotes). Instead, beta-oxidation happens in the cytosol.
Name the three main products of beta-oxidation.
Acetyl-CoA, NADH, and FADH2
Beta-oxidation gets it name from the carbon on a fatty acid molecule that is positioned ________ carbon(s) away from the carbonyl carbon.
Beta-oxidation gets it name from the carbon on a fatty acid molecule that is positioned two carbon(s) away from the carbonyl carbon.
The beta carbon is adjacent to the alpha carbon, which is adjacent to the carbonyl carbon.
True or false:
Free fatty acids in the cell cytosol can diffuse into the mitochondria, where they later undergo beta-oxidation.
False
A free fatty acid is negatively-charged due to the presence of a carboxylate group. Such charged (and therefore highly polar) molecules cannot diffuse directly across the mitochondrial membrane(s).
Free fatty acids in the cytosol must undergo what process before they can be transported into the mitochondria?
Activation
This process renders the fatty acid uncharged, after which short-chain activated FAs can simply diffuse into the mitochondria, while larger activated FAs are brought in via a specialized shuttle system.
In fatty acid activation, a free fatty acid is transformed into a molecule called a fatty acyl-CoA. Predictably, this is simply the fatty acid attached to coenzyme A (CoA). Which enzyme catalyzes this reaction?
Long-chain fatty acyl-CoA synthetase
This enzyme is alternatively termed long-chain fatty acyl-CoA ligase. This is in keeping with the definition of a ligase, which is an enzyme that catalyzes the attachment of two molecules into a single, larger molecule.
True or false:
Fatty acid activation requires ATP.
True
Fatty acid activation, or the transformation of a free fatty acid into a fatty acyl-CoA, does require energy input in the form of ATP hydrolysis. In fact, ATP is a reactant of this process, and AMP is a product.
Unlike small- to medium-chain fatty acids, small- to medium-chain fatty acyl-CoA molecules can diffuse directly into the mitochondria because they are less:
polar.
Polarity is the most important determinant of whether a substance can diffuse across a biological membrane. The less polar the molecule, the more easily it can diffuse.
What is the purpose of the carnitine shuttle?
The carnitine shuttle functions to transport long-chain and very long-chain fatty acids (FAs) across the inner mitochondrial membrane.
Short- and medium-chain FAs, once activated, can simply diffuse into the inner compartment of the mitochondria, but longer FAs are too large and must be specifically transported.
Once a fatty acid is activated and transported into the mitochondria, beta-oxidation takes place as a repeated series of how many steps?
Four steps
Put simply, beta-oxidation is essentially a series of four steps repeated over and over. Each four-step cycle releases one acetyl-CoA, one NADH, and one FADH2 molecule.
The first of the four key steps of beta-oxidation involves the formation of a trans double bond between the second and third carbons and the associated reduction of FAD to FADH2. A member of which class of enzyme catalyzes this reaction?
An oxidoreductase (specifically, a dehydrogenase)
The full name of the enzyme that catalyzes this step is fatty acyl-CoA dehydrogenase. However, you are much more likely to be asked to realize that the reduction of FAD must be performed by an oxidoreductase than to be asked the specific identity of this enzyme.
The second of the four key steps of beta-oxidation involves the addition of -OH to one side of the double bond between carbons 2 and 3, rendering it a single bond. What molecule is also involved in this reaction?
Water (H2O)
The enzyme that catalyzes this step is enoyl-CoA hydratase, the name of which may help answer this question. However, even without this information, we know that an -OH was added to one side of the bond. To render it a single bond, an -H must have been added to the other side, indicating that H2O was involved.
The third main step of beta-oxidation, catalyzed by β-hydroxyacyl-CoA dehydrogenase, produces which high-value molecule?
NADH
The enzyme name here tells us that this reaction is a redox reaction. Overall, each round of beta-oxidation produces one molecule each of FADH2, NADH, and acetyl-CoA. FADH2 was produced in step 1, and acetyl-CoA is produced in step 4, leaving NADH to be produced here, in step 3.
The final step of beta-oxidation involves breakage of the molecule into a shorter acyl-CoA and:
acetyl-CoA.
Acetyl-CoA, a biologically important molecule, is the main product of beta-oxidation. This molecule can then be used in other metabolic processes, such as the Krebs cycle.
