Metabolism for the DAT
/Learn key DAT concepts related to carbohydrate, lipid, and amino acid metabolism, and photosynthesis, plus practice questions and answers
Everything you need to know about metabolism for the dat
Table of Contents
Part 1: Introduction to metabolism
Part 2: Carbohydrate metabolism
a) Glycolysis and fermentation
b) Pyruvate metabolism and TCA cycle
c) Electron transport chain and oxidative phosphorylation
Part 3: Other metabolic pathways
a) Lipid metabolism
b) Amino acid metabolism
Part 4: Photosynthesis
a) Light-dependent and light-independent reactions
b) Photorespiration and other types of photosynthesis
Part 5: High-yield terms
Part 6: Questions and answers
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Part 1: Introduction to metabolism
Understanding metabolism is crucial for comprehending the intricate processes that regulate energy production and utilization within the human body. Cells that make up our body have key reactions like metabolism to maintain homeostasis. Therefore, it is important to understand cell metabolism and regulation. This guide will teach you everything you need to know about metabolism and cellular respiration for the DAT. As you study, pay close attention to any bolded terms. These are high-yield terms you need to know for the exam. When you are ready, test yourself with practice questions and answers at the end of the guide.
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Part 2: Carbohydrate metabolism
Carbohydrates serve as one of the primary sources of energy for the body, providing readily available fuel for cellular processes. Through a series of enzymatic reactions, carbohydrates are broken down into simpler sugars such as glucose.Glucose can be further metabolized to produce adenosine triphosphate (ATP), the energy currency of cells.
Carbohydrates can be classified based on their number of components as monosaccharides, disaccharides, and polysaccharides. First, monosaccharides are carbohydrate monomers or single units. Two monosaccharides can be attached via a glycosidic linkage to form a disaccharide. Multiple monomers that are linked together form a polysaccharide. For a review of carbohydrates, see our guide on biomolecules.
Carbohydrate metabolism starts in the oral cavity, with specific enzymes breaking down carbohydrates into more easily digestible molecules. Specifically, salivary amylase, found in saliva, breaks down polysaccharides into smaller subunits in the mouth. Further along in the small intestine, pancreatic amylase breaks down the carbohydrates further. Eventually, carbohydrates are broken down into three monosaccharides: glucose, galactose, and fructose.
At this point, these free glucose molecules can be built into glycogen for long-term storage. This process is known as glycogenesis.
a) Glycolysis and fermentation
One of the main pathways of carbohydrate metabolism is glycolysis. Glycolysis is the metabolic pathway where a glucose molecule is enzymatically converted into two molecules of pyruvate. This process predominantly takes place in the cytoplasm of cells. Alongside the production of 2 pyruvate molecules, each glucose undergoing glycolysis yields 2 NADH and 4 ATP molecules. Notably, 2 ATP molecules are initially invested to initiate glycolysis, resulting in a net gain of 2 ATP. Therefore, the net products of glycolysis include 2 pyruvate molecules, 2 NADH molecules, and a net gain of 2 ATP molecules.
While the accompanying diagram illustrates all steps of glycolysis, only certain steps yield significant products. Memorization of every enzymatic step in glycolysis is not required; however, understanding the function of key enzymes is beneficial.
FIGURE 1: OVERVIEW OF GLYCOLYSIS
The key steps of glycolysis are outlined below:
Step 1: Hexokinase/Glucokinase
Glucokinase is primarily found in hepatocytes (liver cells) and pancreatic β-islet cells, activated by insulin. Hexokinase, in contrast, is present in most tissues. Both enzymes share the role of catalyzing the irreversible phosphorylation of glucose using ATP.
The resulting product, glucose 6-phosphate, cannot freely exit the cell. Additionally, glucose 6-phosphate exerts inhibitory feedback on hexokinase.
Step 3: Phosphofructokinase 1 (PFK-1)
Phosphofructokinase 1, or PFK-1, governs the rate-limiting step of glycolysis. This step is converting fructose 6-phosphate into fructose 1,6-bisphosphate using ATP, is highly regulated.
Consider the balance between when energy is needed versus conserved. When more energy production is not needed, citrate (from aerobic respiration) and ATP inhibit PFK-1, signaling sufficient cellular energy levels and reducing the immediate need for glycolysis. This step is not irreversible, and so suppressing this reaction allows the cell to conserve energy. However, if energy production needs are increased, such as the presence of AMP (adenosine monophosphate), this would activate PFK-1.
Step 6: G3P Dehydrogenase
G3P dehydrogenase facilitates the reversible conversion of glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate, generating NADH. Given that one glucose molecule yields two glyceraldehyde 3-phosphate molecules, this step results in two NADH molecules per glucose.
Step 7: Phosphoglycerate Kinase
Phosphoglycerate kinase catalyzes the reversible conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate, liberating one ATP per phosphoglycerate molecule (or 2 ATP per glucose molecule).
Step 10: Pyruvate Kinase
Pyruvate kinase, the final enzyme in glycolysis, converts PEP into pyruvate irreversibly, yielding ATP. This step produces one ATP per phosphoenolpyruvate molecule (or 2 ATP per glucose molecule).
Glycolysis naturally occurs under aerobic conditions, meaning oxygen is present. Another reaction to consider, though, is lactic acid fermentation when there is no oxygen for energy production. Under anaerobic conditions, pyruvate molecules produced from glycolysis undergo fermentation, facilitated by lactate dehydrogenase. This enzyme catalyzes the conversion of pyruvate into lactate, yielding NAD+ as a byproduct. As the sole enzyme involved, lactate dehydrogenase determines the rate of this process.
Why do our cells engage in lactic acid fermentation, even though it doesn't directly produce ATP? The primary aim of lactic acid fermentation is to regenerate NAD+, which is necessary for sustaining glycolysis. Glyceraldehyde 3-phosphate dehydrogenase consumes NAD+ during glycolysis, converting it to NADH. By generating lactate, additional NAD+ becomes available for glycolytic enzymes to continue producing ATP in increments of two.
Lactic acid fermentation is part of the broader lactic acid cycle, also known as the Cori cycle. Muscular lactate is transported via the bloodstream to the liver, where specialized enzymes convert it back into glucose. This glucose is then redistributed to the muscles to sustain energy production.
FIGURE 2: LACTIC ACID CYCLE
For periods where the body needs more readily available glucose, such as during exercise or fasting, energy needs are sustained through gluconeogenesis. Gluconeogenesis is a metabolic pathway that synthesizes glucose using precursors derived from alternative sources like lipids (fatty acids) or amino acids.
In essence, gluconeogenesis mirrors the reverse of glycolysis. Precursor molecules, such as pyruvate derived from lactate, amino acids, or glycerol, are converted into glucose through a series of enzymatic reactions. Several enzymes utilized in glycolysis also partake in gluconeogenesis but perform their reactions in reverse.
Unlike glycolysis, which is largely exergonic (releases energy), gluconeogenesis requires additional ATP input at certain steps to drive these energetically unfavorable reactions. Therefore, enzymes catalyzing rate-limiting steps in glycolysis have counterparts in gluconeogenesis that necessitate the expenditure of ATP molecules to proceed spontaneously and synthesize glucose.
This intricate metabolic process ensures a constant supply of glucose that is vital for meeting energy demands, especially when glucose availability from traditional sources is limited. Gluconeogenesis plays a critical role in maintaining blood glucose levels during periods of fasting or intense physical activity when glycogen stores are depleted, contributing to overall metabolic flexibility and homeostasis.
b) Pyruvate metabolism and TCA cycle
From the cytoplasm of the cell, we now move into the mitochondria. The mitochondria contains an outer and inner mitochondrial membrane, an intermembrane space, and a mitochondrial matrix.
FIGURE 3: STRUCTURE OF MITOCHONDRIA
Under aerobic conditions, pyruvate molecules generated by glycolysis undergo a crucial transition in the mitochondrial matrix. Here, the enzyme pyruvate dehydrogenase catalyzes the irreversible conversion of pyruvate into acetyl-CoA, producing NADH and carbon dioxide as byproducts. Notably, acetyl-CoA acts as a negative feedback inhibitor of pyruvate dehydrogenase, regulating its own production.
It's important to highlight that pyruvate dehydrogenase is distinct from both glycolysis and the citric acid cycle. Rather, this enzyme functions as an intermediary, facilitating the transition between these two metabolic pathways. This pivotal step enables the further utilization of pyruvate-derived acetyl-CoA in the citric acid cycle to generate ATP through oxidative phosphorylation, highlighting the interconnected nature of cellular metabolism.
In the mitochondrial matrix, acetyl-CoA enters the citric acid cycle, also known as the Krebs cycle. Despite not directly using oxygen in its reactions, the citric acid cycle is considered aerobic because it requires the continuous regeneration of electron carriers, specifically NAD+ and FAD, which ultimately depends on the presence of oxygen.
During the citric acid cycle, NAD+ and FAD are reduced to NADH and FADH2, respectively, as acetyl-CoA undergoes oxidation. These reduced forms of electron carriers serve as crucial intermediates that donate electrons to the electron transport chain (ETC) for ATP production. Importantly, in the ETC, oxygen acts as the final electron acceptor by combining with hydrogen ions to form water. Without oxygen, the electron transport chain would be unable to regenerate NAD+ and FAD, halting the citric acid cycle.
FIGURE 4: OVERVIEW OF CITRIC ACID CYCLE
The diagram above shows the citric acid cycle. You don’t need to know all of the enzymes involved, but you should be familiar with the overall start and end products of the cycle. Each acetyl-CoA molecule entering the citric acid cycle results in the production of 1 GTP (or ATP equivalent), 3 NADH, 1 FADH2, and 2 CO2 molecules. Given that one glucose molecule generates two acetyl-CoA molecules, the complete citric acid cycle from glucose yields 2 GTP, 6 NADH, 2 FADH2, and 4 CO2, demonstrating the energetic efficiency of aerobic metabolism.
c) Electron transport chain and oxidative phosphorylation
Now that we have our core products from the citric acid cycle, we are at the final step to producing ATP for readily available energy for our body. Let's delve into the intricate workings of the electron transport chain (ETC) and the pivotal role played by electron carriers like NADH and FADH2.
After being generated during glycolysis and the citric acid cycle, NADH and FADH2 deliver their electron cargo to the ETC, a series of redox reactions that occur along the inner mitochondrial membrane. However, there's a catch—these electron carriers cannot freely cross the mitochondrial membrane from the cytoplasm. To overcome this barrier, shuttle systems such as the glycerol 3-phosphate (G3P) shuttle and the malate-aspartate shuttle transport electron equivalents into the mitochondria.
Once inside, the electrons flow through a sequence of four membrane-bound complexes located in the inner mitochondrial membrane. These complexes are enzymatic assemblies, with several belonging to the flavoprotein class of enzymes that utilize FAD as an electron acceptor and transporter. Here are the first four complexes of the ETC:
Complex I: This complex accepts electrons from NADH and transfers them to ubiquinone (coenzyme Q), pumping protons from the mitochondrial matrix into the intermembrane space.
Complex II: Unlike the other complexes, complex II is not involved in proton pumping. It directly links to the citric acid cycle by oxidizing succinate to fumarate, transferring electrons to ubiquinone.
Complex III: This complex receives electrons from ubiquinone and passes them to cytochrome c, while actively pumping protons across the inner mitochondrial membrane.
Complex IV: The final complex in the chain, complex IV, receives electrons from cytochrome c and transfers them to oxygen (the final electron acceptor), generating water. Protons are pumped across the membrane during this process.
FIGURE 5: COMPLEXES OF THE ELECTRON TRANSPORT CHAIN
The movement of electrons through these complexes releases energy used to pump protons from the mitochondrial matrix into the intermembrane space, establishing an electrochemical gradient. This gradient powers ATP synthesis via oxidative phosphorylation, illustrating the crucial link between electron transport and ATP production in aerobic metabolism. While memorization of specific complex names may not be required, understanding their functions and overall role in cellular respiration is fundamental to grasp the intricacies of mitochondrial energy production.
Three out of the four complexes in the ETC actively pump protons (H+ ions) from the mitochondrial matrix into the intermembrane space. This proton pumping serves two critical purposes: it creates an electrical gradient due to the positive charge carried by the protons, and it establishes a chemical gradient due to the resulting decrease in pH (increased acidity) in the intermembrane space. This combined electrochemical gradient is commonly known as the proton-motive force.
Memorizing the proton-pumping details associated with NADH and FADH2 donation to the ETC is useful for understanding ATP production efficiency:
- For each molecule of NADH, a total of 10 protons are pumped into the intermembrane space: 4 protons at complex I, 4 protons at complex III, and 2 protons at complex IV.
- In contrast, each molecule of FADH2 results in the pumping of 6 protons into the intermembrane space: 4 protons at complex III and 2 protons at complex IV.
To maintain the integrity of the electrochemical gradient, it is crucial for both the outer and inner mitochondrial membranes to be impermeable to proton leakage. If protons were to leak back into the mitochondrial matrix, the gradient would dissipate, compromising ATP synthesis efficiency. Therefore, the selective impermeability of the mitochondrial membranes ensures the stability and sustainability of the proton-motive force, optimizing ATP production for cellular energy needs. Understanding these intricate processes sheds light on the remarkable efficiency and precision of mitochondrial energy metabolism.
The electrochemical gradient generated by the proton-motive force drives the synthesis of ATP by ATP synthase, an enzyme embedded in the inner mitochondrial membrane. ATP synthase utilizes the energy derived from the proton gradient to convert ADP (adenosine diphosphate) and inorganic phosphate (Pi) into ATP (adenosine triphosphate) through a process known as oxidative phosphorylation. Oxidative phosphorylation involves the coupling of energy released during the oxidation of NADH and FADH2 to the formation of a new bond between ADP and inorganic phosphate, resulting in the production of ATP.
Within the inner mitochondrial membrane, the enzyme ATP synthase (also known as complex V) spans across and consists of two main components: F0 and F1. The F0 component forms a channel through which protons (H+ ions) flow from the intermembrane space into the mitochondrial matrix, a phenomenon known as chemiosmosis. Meanwhile, the F1 component utilizes the energy derived from the proton gradient to catalyze the phosphorylation of ADP into ATP. This process involves conformational changes induced by the rotational movement of the F1 component, earning ATP synthase the nickname of a "molecular motor."
Now, let's review the net products of aerobic respiration, considering glycolysis, pyruvate oxidation, and the citric acid cycle:
- For each NADH molecule generated during these processes, approximately 2.5 ATP molecules are produced.
- For each FADH2 molecule generated, approximately 1.5 ATP molecules are produced.
Given these ATP yield calculations, aerobic respiration culminates in a grand total of approximately 32 ATP molecules generated per glucose molecule. This comprehensive energy production is essential for meeting the cellular energy demands required for various biological processes, highlighting the efficiency and complexity of aerobic metabolism. Understanding these principles is crucial for grasping the interplay between cellular respiration pathways and ATP synthesis in living organisms.
| Process | Net Products/Glucose Molecule |
|---|---|
2 ATP |
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2 FADH2 → 3ATP 2GTP → 2ATP |
|
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