Ah glycolysis, the dread of every premed student that is initially felt in their biochemistry class and once more while studying for the MCAT. Luckily, there are only a few things that you need to know about glycolysis for the MCAT. We’re going over a few easy MCAT glycolysis explanations to better ingrain and understand these topics and eventually the first year of medical school.
Everything You Need to Know About Glycolysis for the MCAT
The Importance of Glucose
Let’s first start with the basics to provide an easy glycolysis explanation. Polysaccharide sugars, from your diet, are broken down into their monosaccharide subunits. One important monosaccharide is glucose. Glucose has six carbons that are bound to oxygen molecules and whose bonds contain energy. Your body’s goal is to break down glucose and utilize the energy stored in these bonds to produce ATP. When you eat that slice of pumpkin pie on Thanksgiving, there are a lot of processes that must occur to turn the glucose molecules in the pie into energy.
Insulin and Transporters
First, amylase enzymes secreted in the saliva and pancreatic juices help break down these complex polysaccharides into their monosaccharide subunits. These monosaccharides subunits are polar, meaning they are hydrophilic. These hydrophilic molecules are absorbed via the intestinal cells and secreted into the blood.
When glucose levels in the blood rise, insulin is stimulated and released from beta-islet cells in the pancreas. Insulin promotes increased expression of glucose channel (GLUT4) transporters in cells throughout your body. GLUT4 transporters have a low KM, or high affinity, for glucose molecules. This causes increased uptake of glucose into your cells and drops in blood glucose levels.
The Initial Steps of Glycolysis
Once glucose is absorbed into your cells from the blood, glycolysis begins. The first step of glycolysis is to “activate” the glucose molecule for breakdown via phosphorylation. The phosphate group added to glucose comes from ATP, so, naturally, ATP → ADP is required in the first step. The enzyme responsible for this is hexokinase (or glucokinase if in hepatocytes). Since an energetic bond from ATP was broken this step is considered irreversible, and thus, an important testing opportunity.
Key Regulatory Steps in Glycolysis
The next steps of glycolysis are not as important until we reach phosphofructokinase 1 (PFK-1). PFK-1 is an interesting step. What’s important to know about PFK-1 is that it is inhibited by high ATP concentrations and citrate and activated by AMP. Let’s think about this: if you have high ATP and citrate concentrations in your body, and that means you have high levels of energy. If you have high levels of energy, then you don’t need to break down glucose to make more energy. Therefore, this step is inhibited by high levels of ATP and citrate.
Conversely, if you have high AMP concentrations, then you have low energy levels in your body. Although ATP inhibits PFK-1 activity, PFK-1 requires energy from ATP to catalyze the reaction. Therefore, this is an irreversible step.
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Now, you may be asking: if I have high energy levels (high ATP concentrations) and I still eat some pumpkin pie, will all that extra glucose continue to stay in my blood (or reside in my cells) since I don’t need to break it down?
The answer is no. Remember, insulin is released under high blood glucose concentrations. If you have high ATP concentrations already, then insulin will promote the storage of glucose as fatty acids or glycogen. Since you will need to break down glucose for the creation of fatty acids, it is important to note that insulin indirectly overrides the inhibiting effects of high ATP concentrations on PFK-1.
The metabolites of PFK-1 are further broken down into 2-three carbon units. Remember that glucose has six carbons. It is important to note that every reaction from here on is done twice—one for each three-carbon unit. These metabolites are further altered in a series of reactions that are not as important on the MCAT. However, it is important to know that during this process each of these three carbon units produce one ATP molecule. Net two ATP so far.
The Final Stages of Glycolysis
The last and final step of glycolysis is converting phosphoenolpyruvate (PEP) into pyruvate via the enzyme pyruvate kinase. This last step is important because it takes the energy of a phosphate bond on PEP and transfers it to a molecule of ADP, creating ATP. Since we have two PEP molecules being converted into two pyruvate molecules, we net a total of two ATP from this reaction.
From here, the pyruvate created will be transported into the mitochondrial matrix for further breakdown within the pyruvate dehydrogenase complex to ultimately shuttle to the Krebs cycle or fatty acid synthesis.
Summary and Key Enzymes of Glycolysis for the MCAT
In summary, we took one glucose (a six-carbon molecule) and broke it down into two pyruvates (three-carbon molecule). Throughout this process, we required two ATP to activate glycolysis and we produced four ATP molecules in the end. The three important enzymes to know are hexokinase, phosphofructokinase, and pyruvate kinase, each of them being an irreversible step in glycolysis.
Further Reading
MCAT Glycolysis and Beyond: Introducing Gluconeogenesis
Ponder on this: if these three reactions in glycolysis are irreversible and the rest are reversible, and if we are going in the reverse direction (to create glucose molecules), then we must replace only these three irreversible enzymes with other enzymes to be able to go backward. That is called gluconeogenesis.
Glycolysis and Gluconeogenesis with Enzyme Names
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