Undergraduate students of biochemistry may know the sequence of reactions in different pathways of energy metabolism. But how well do they understand the interconnections between these pathways? Maya Murdeshwar, an educator from St. Xavier’s College, Mumbai, uses a quiz featuring cheetahs, triathlons and monozygotic twins to test her students and uncover their misconceptions about these pathways. She explains her approach in this article.
A question I often pose to my undergraduate Biochemistry and Nutrition class is about energy sources – what fuels the human body? The answer invariably is ‘glucose’ or ‘carbohydrates’. Rarely ever does a student answer ‘fats’ or ‘proteins’.
While carbohydrates serve as the chief fuel source for the body, they are definitely not the only source. The human body is capable of preferentially utilizing carbohydrates, fats, proteins, phosphocreatine and ketone bodies as energy sources under different conditions. This depends upon a variety of factors like the availability of oxygen (abundant/lacking), the presence or absence of sub-cellular structures (mitochondria) and associated enzymes, the physiological state of the body (fasting/fed), the intensity and duration of the physical activity being performed (resting/mild/moderate/heavy) and the tissue that is metabolizing the energy (muscle/liver/brain/heart/adipose). Students find it difficult to comprehend this distinction even after an in-depth study of individual energy metabolizing pathways. The integration of various energy metabolizing pathways proves to be a challenge for them.
One reason could be the greater emphasis laid on carbohydrate metabolism in classroom teaching at the high school and undergraduate levels. A substantial amount of time is spent on glycolysis and the Kreb’s cycle, the central pathways for carbohydrate breakdown, as compared to that spent on lipolysis (fat breakdown) and amino acid oxidation (protein breakdown). Compartmentalization of these topics into separate chapters in standard textbooks facilitates their in-depth study, but creates invisible barriers in the minds of students, making it difficult to comprehend the intertwined nature of the metabolic web.
Both fat and protein metabolism feed into carbohydrate metabolism at various points, ensuring their efficient utilization as alternative energy sources. Textbooks usually deal with this integration in a separate chapter towards the end of the book. While this might seem logical, it is equally important to mention the interconnections at relevant places in individual chapters. This will help students to connect the dots and understand the bigger picture. Additionally, topics of integrative nature are usually taught towards the end of the course, after the individual pathways and cycles have been explained in detail. The lack of time at this stage makes the instructor hurry through these topics, leaving students with less time to assimilate them. The onus then lies on the instructor to devote adequate time to highlight these interconnections and cite appropriate examples to provide students with the necessary context to understand and appreciate them.
To help students understand the general and special cases in energy metabolism, I use the questioning approach and, if time permits, peer learning through POGIL sheets. Gentle probing helps identify the flaws in their understanding:
What is the chief source of energy for the human body?
Can any other sources be used?
If yes, under which conditions are these alternative sources utilized?
Is energy metabolism during short and long-term fasting the same as in a well-fed state?
Which fuel source does the body use when at rest as opposed to exercising? Do you think this would change if the intensity and duration of the exercise changes?
When would the body burn the most fat – during light, moderate or heavy exercise?
Which energy sources fuel Strength (Sprint/Swim/Weight Lifting) vs Endurance training? (Marathon/Triathlon/Tour de France)
A crocodile expends large amounts of energy in a short period to catch its prey. A cheetah hunts down its prey after a short, intense chase. Is there any difference in the way they metabolize energy?
Would the energy metabolism of monozygotic identical twins differ considering they have exactly identical genetic constitutions? Consider one to be a triathlete and another a truck driver. Does nature versus nurture play a role in energy metabolism?
Questions like these, while capturing the interest of students, also put their learning into context. It makes them think deeper and apply concepts ‘across textbook chapters’. From textbooks that confound them with structures and reactions, they are transported back into a familiar world. It gives them a chance to explore the immense possibilities that the integration of metabolic pathways has to offer, better clarity on the bigger picture, and proper closure to the topic under study. More importantly, it leaves them with a deeply humbling appreciation for the intricately woven web of life.
A brief explanation of the key concepts in energy metabolism is as follows:
‘Energy metabolism’ is the process of generating energy from consumed food. Through a series of biochemical reactions and interconnected pathways, nutrients are systematically broken down to generate adenosine triphosphate (ATP), the usable form of energy. In the presence of oxygen, a complete breakdown of nutrients to carbon dioxide and water occurs in a process termed ‘aerobic respiration’ (aerobic = requiring oxygen) that occurs in membrane-bound structures within the cell called ‘Mitochondria’ (singular: Mitochondrion). This process generates large amounts of ATP. On the other hand, when the oxygen supply is deficient, the body switches to ‘anaerobic’ respiration (anaerobic = lacking oxygen) that occurs in the cell cytoplasm and generates comparatively lesser ATP. The human body thus prefers aerobic over anaerobic respiration.
Carbohydrates, fats and proteins, in that order, act as fuel sources for the body. While carbohydrates are the chief source of energy in a well-fed state, fats and the ketone bodies formed from fats act as fuels in the fasting state. Only under prolonged starvation or the continued absence of proteins in the diet, does the body resort to breaking down its own protein, a condition termed ‘wasting’ that ultimately results in death. This preferential usage is because the breakdown of carbohydrates requires much less oxygen than that of fats and proteins.
Energy metabolism is best explained in terms of exercise. In the resting state and during mild exercise, the body receives an adequate supply of oxygen. This promotes the utilization of fats as fuel [Figure 1]. During moderate exercise, oxygen availability decreases slightly, recruiting carbohydrates for energy production. Both carbohydrates and fats are aerobically broken down in equal measure. In contrast, under oxygen-limiting conditions like high-intensity exercise (sprint/swim/weight lifting) and strength training (activities that require large bursts of energy in a short period of time), the body switches to anaerobic respiration.
The sudden burst of activity at the start necessitates ATP to be synthesized almost instantaneously. This is achieved by utilizing a high-energy compound called phosphocreatine, whose limited reserves can sustain 20 – 30 seconds of intense activity [Figure 2]. In order to continue, the body switches to anaerobic respiration. Oxygen being in short supply, fats are not metabolized at this stage. Thus, contrary to popular belief, high-intensity exercise burns carbohydrates, not fat. Additionally, anaerobic respiration causes the build-up of lactic acid in the tissue causing cramps and intense pain termed ‘muscle fatigue’. The activity can no longer be sustained, thus stopping completely, or slowing down the pace. Deep, heavy breathing at this point compensates for the oxygen deficit, causing aerobic respiration to resume.
The lactic acid build-up is the reason why crocodiles and cheetahs follow up the high-intensity ambush of their prey with long periods of rest and recovery. On the other hand, endurance sports enthusiasts like marathon runners, triathletes and Tour de France contestants (who require small amounts of energy over a long period of time) function mainly on aerobic respiration, mainly burning fat. They have well-developed lungs and a strong healthy heart that ensure a steady and adequate supply of oxygen for the entire duration of the activity. Burning of fat thus spares carbohydrates for the intense speed required towards the finish of the race. This active lifestyle of a triathlete over the sedentary one of his truck driver identical twin is the reason why nurture seems to play a bigger role than nature and genetics in this case.
Another misunderstanding of a related concept is with respect to slow and fast twitch muscle fibres. The slow twitch (red) muscle fibres present in our legs are densely populated with mitochondria. The fast twitch (white) muscle fibres present in the eyes have fewer mitochondria. When asked which of these fibres play a greater role in high-intensity activities, students usually answer ‘red’ fibres since they have more mitochondria, forgetting the fact that high-intensity activity creates an oxygen deficit that prevents mitochondria from aerobically respiring. A proper understanding of energy metabolism and associated concepts will help students overcome such misconceptions.