Iron Metabolism
Describe the difference between heme and non-heme iron in terms of dietary sources, absorption, and chemical form in the duodenum.
Heme iron comes from animal sources such as meat, poultry, and fish. It is bound within the heme molecule and is absorbed efficiently in the duodenum, largely independent of other dietary factors. Heme iron is absorbed directly as Fe²⁺ after the heme group is broken down in the enterocyte.
Non-heme iron is found mainly in plant sources (e.g., legumes, grains, vegetables) and exists primarily as Fe³⁺, which is less soluble and less readily absorbed. In the duodenum, non-heme iron must first be reduced from Fe³⁺ to Fe²⁺ by a ferric reductase enzyme before it can be transported into the enterocyte. Non-heme iron absorption is influenced by dietary enhancers (e.g., vitamin C) and inhibitors (e.g., phytates, polyphenols).
Why is pepsin secreted as the inactive zymogen pepsinogen?
To prevent self-digestion of the stomach lining; pepsinogen is only activated to pepsin in the acidic environment of the stomach.
Compare aerobic and anaerobic glucose metabolism in terms of oxygen requirement, location in the cell, and ATP yield.
Aerobic glucose metabolism requires oxygen and occurs in both the cytoplasm (glycolysis) and mitochondria (pyruvate oxidation, citric acid cycle, and electron transport system). Glucose is fully oxidized to CO₂ and H₂O, and the high-energy electrons are transferred to NADH and FADH₂, which drive the electron transport system to generate a large amount of ATP (≈30–36 ATP per glucose molecule). Aerobic metabolism is efficient and supports sustained energy production in tissues like skeletal muscle, heart, and liver.
Anaerobic glucose metabolism does not require oxygen and occurs entirely in the cytoplasm. Glycolysis converts glucose into pyruvate, which is then reduced to lactate to regenerate NAD⁺ so glycolysis can continue. ATP yield is much lower, producing only 2 ATP per glucose molecule, but it allows rapid energy production when oxygen is limited, such as during intense exercise or in red blood cells.
Explain the role of bile salts in lipid digestion. How do they interact with dietary fats, and why are they necessary for efficient lipase activity?
Bile salts are amphipathic molecules synthesized from cholesterol in the liver and secreted into the small intestine via bile. Their amphipathic nature allows them to interact with both water and lipids, which enables them to emulsify large fat droplets into smaller droplets with increased surface area.
By forming these emulsified droplets, bile salts create a greater surface for lipases (lingual, gastric, and pancreatic) to act on, allowing more efficient hydrolysis of triglycerides into free fatty acids and monoglycerides. After digestion, bile salts aggregate with fatty acids and monoglycerides to form micelles, which facilitate transport to the enterocyte membrane for absorption.
Without bile salts, lipid digestion would be inefficient, as lipases can only act at the surface of lipid droplets, and large droplets have a relatively small surface area. Additionally, bile salts are recycled via enterohepatic circulation, making them an essential component of ongoing fat digestion.
Bile salts emulsify dietary fats to increase surface area, enhance lipase activity, and form micelles that enable fatty acid and monoglyceride absorption, making them critical for effective lipid digestion.
Define nutrition, digestion, absorption, and metabolism. How are these processes interconnected to maintain energy and nutrient homeostasis?
Nutrition is the process of providing or obtaining the food necessary for health, growth, and maintenance. It includes the intake of macronutrients, micronutrients, and water that support bodily functions.
Digestion is a catabolic process that breaks down complex food molecules into their chemical building blocks. For example, carbohydrates are broken into monosaccharides, proteins into amino acids, lipids into fatty acids and glycerol, and nucleic acids into nucleotides. Digestion primarily occurs through enzymatic hydrolysis, in which water molecules are used to cleave chemical bonds.
Absorption is the process by which nutrients are transferred from the lumen of the gastrointestinal tract into the body, typically via capillaries in the intestinal villi, and delivered to tissues through the hepatic portal system or lymphatic circulation.
Metabolism encompasses all biochemical reactions in the body, including:
Anabolism: building complex molecules from smaller ones (e.g., glycogenesis, protein synthesis)
Catabolism: breaking down complex molecules to release energy (e.g., glycolysis, lipolysis)
These processes are interconnected to maintain energy and nutrient homeostasis: nutrients obtained through nutrition are digested into absorbable forms, absorbed into the bloodstream or lymph, and then metabolized to provide ATP, building blocks, or precursors for biosynthesis. Efficient coordination ensures that energy demands are met, essential molecules are supplied, and nutrient balance is maintained over time.
Describe how the body stores iron and under what conditions.
The body stores iron primarily in hepatocytes (liver cells) and macrophages in the spleen and liver. Ferritin is the main, soluble storage form and serves as temporary iron storage that can be readily mobilized when the body needs iron for processes like hemoglobin synthesis. Iron storage increases when dietary iron intake exceeds the body’s needs or when iron is not being used for erythropoiesis. Conversely, stored iron is mobilized during iron deficiency, increased erythropoiesis, or blood loss to maintain plasma iron levels and support hemoglobin synthesis. This dynamic storage system ensures the body maintains iron homeostasis while minimizing the risk of deficiency or toxicity.
Identify the nitrogen balance state:
Growing child → ______
Healthy adult → ______
Starvation or trauma → ______
Growing child → POSITIVE
Healthy adult → EQUILIBRIUM
Starvation or trauma → NEGATIVE
Explain how insulin and glucagon act as opposing hormones to regulate blood glucose levels, and provide examples of when each hormone is active.
Insulin and glucagon are antagonistic hormones secreted by the pancreas that regulate blood glucose levels. Insulin, released by β-cells after a meal when blood glucose is high, promotes glucose uptake into cells (especially muscle and adipose tissue) by stimulating GLUT4 translocation to the plasma membrane. Insulin also stimulates glycogenesis (storage of glucose as glycogen) and lipogenesis, lowering blood glucose back to normal.
Glucagon, secreted by α-cells when blood glucose is low (fasting, between meals, or during exercise), promotes glycogenolysis (breakdown of glycogen to glucose) and gluconeogenesis (production of new glucose from non-carbohydrate precursors) in the liver. Glucagon ensures a continuous supply of glucose to tissues that rely on it, such as the brain and red blood cells.
Insulin active: After eating a carbohydrate-rich meal, blood glucose rises → insulin is released → glucose stored and blood sugar decreases.
Glucagon active: Overnight fasting or prolonged exercise → blood glucose drops → glucagon is released → liver releases glucose to maintain homeostasis.
Insulin lowers blood glucose by promoting uptake and storage, while glucagon raises blood glucose by mobilizing and producing glucose; together, they maintain blood glucose homeostasis.
Compare and contrast the functions of lingual, gastric, and pancreatic lipases. Include their site of secretion, location of action, and specific substrates.
Lingual lipase is secreted by serous glands on the tongue and begins lipid digestion in the mouth and continues in the stomach. Its primary substrate is triglycerides, and it hydrolyzes them into diglycerides and free fatty acids. Lingual lipase is particularly important in infants, who rely heavily on milk fats, and it is acid-stable, allowing it to remain active in the stomach’s low pH.
Gastric lipase is secreted by chief cells in the stomach and acts within the acidic environment of the stomach. Like lingual lipase, it hydrolyzes triglycerides into diglycerides and free fatty acids, contributing to partial lipid digestion. Its activity is limited due to the small surface area of fat droplets in the stomach, making digestion relatively inefficient without emulsification.
Pancreatic lipase is secreted by the pancreas into the small intestine (duodenum), where it is the primary enzyme responsible for triglyceride digestion. It hydrolyzes triglycerides into monoglycerides and free fatty acids, which can be absorbed by enterocytes. Its activity is greatly enhanced by bile salts, which emulsify fats and increase the surface area available for enzymatic action.
Lingual and gastric lipases act early in digestion in the mouth and stomach, partially breaking down triglycerides into diglycerides and fatty acids, whereas pancreatic lipase completes lipid digestion in the small intestine, producing monoglycerides and free fatty acids for absorption. The efficiency of digestion increases as the site progresses and with the presence of bile salts.
Describe the difference between macronutrients and micronutrients. Include their primary functions and examples of each.
Macronutrients are nutrients required by the body in large amounts. Their primary functions include:
Supplying energy – carbohydrates and fats are the main energy sources.
Providing building blocks – proteins supply amino acids for growth, repair, and maintenance of tissues.
Supporting physiological processes – water serves as a medium for chemical reactions, transport, and temperature regulation.
Examples of macronutrients:
Carbohydrates: glucose, starch – energy source
Proteins: amino acids – tissue building and repair
Lipids (fats): fatty acids and triglycerides – energy storage and signaling
Water: medium for biochemical reactions, transport, temperature regulation
Micronutrients are nutrients required in small amounts and do not provide energy, but are essential for regulating body processes. They act as cofactors for enzymes, aid in hormone production, and support structural components such as bones.
Examples of micronutrients:
Vitamins: Vitamin A (vision and gene regulation), Vitamin D (calcium regulation), Vitamin C (antioxidant, collagen synthesis)
Minerals: Iron (oxygen transport), Calcium (bone structure), Magnesium (enzyme cofactor)
Explain the role of transferrin in iron transport. Which tissues primarily receive iron from transferrin, and for what purposes?
Transferrin is a plasma protein that binds ferric iron (Fe³⁺) and transports it through the bloodstream to tissues that require iron. Its main role is to deliver iron safely, preventing free iron from generating reactive oxygen species while ensuring it reaches cells that need it for metabolic processes.
The primary tissues that receive iron from transferrin are:
Bone marrow – Iron is delivered to developing erythrocytes for hemoglobin synthesis, which is essential for oxygen transport.
Muscle cells – Iron is incorporated into myoglobin, which stores oxygen for muscle metabolism and contraction.
Other metabolically active tissues – Iron is used as a cofactor in enzymes involved in oxidative phosphorylation, DNA synthesis, and other cellular processes.
By selectively delivering iron where it is needed, transferrin plays a central role in iron homeostasis and preventing both deficiency and toxicity.
If carbohydrate intake is insufficient, what happens to amino acids and why?
Carbohydrates are the body’s preferred energy source. When they’re lacking, the body shifts to protein catabolism to maintain blood glucose and ATP production. Amino acids are deaminated—their amino groups are removed and excreted as urea—while the remaining carbon skeletons (keto acids) enter metabolism as pyruvate, acetyl-CoA, or citric acid cycle intermediates.
Explain how amylin affects postprandial blood glucose levels, glucagon secretion, and feeding behavior.
Amylin is a peptide hormone co-secreted with insulin by pancreatic β-cells in response to a meal. It helps regulate postprandial blood glucose by slowing gastric emptying, which delays the delivery of nutrients, including glucose, from the stomach to the small intestine. This results in a more gradual rise in blood glucose after eating.
Amylin also suppresses glucagon secretion by inhibiting pancreatic α-cells, preventing the liver from releasing additional glucose when blood sugar is already elevated. Additionally, amylin acts on the brain to promote satiety, reducing food intake during and after meals.
By slowing gastric emptying, suppressing glucagon, and promoting satiety, amylin works with insulin to smooth post-meal glucose fluctuations and help control overall energy intake.
Describe how fatty acids are stored and mobilized in adipose tissue.
Storage of fatty acids occurs in adipose tissue in the form of triglycerides (TGs), which are composed of three fatty acids esterified to a glycerol backbone. When energy intake exceeds energy expenditure, fatty acids from the diet or synthesized via lipogenesis in the liver are transported to adipose tissue, where they are re-esterified into triglycerides and stored in lipid droplets for future use.
Mobilization of fatty acids occurs during fasting, prolonged exercise, or low-carbohydrate intake, when energy demand exceeds glucose availability. In this state, hormone-sensitive lipase (HSL) and other lipases in adipocytes are activated by glucagon, epinephrine, or cortisol, catalyzing lipolysis—the breakdown of triglycerides into free fatty acids and glycerol. These products are then released into the bloodstream:
Free fatty acids bind to albumin and are transported to tissues such as muscle and liver for β-oxidation and ATP production.
Glycerol can be taken up by the liver for gluconeogenesis, contributing to blood glucose maintenance.
Differentiate between water-soluble and lipid-soluble vitamins in terms of absorption, storage, and risk of toxicity. Give examples of each.
Water-soluble vitamins include the B-complex vitamins (e.g., B₁, B₂, B₃, B₆, B₉, B₁₂) and vitamin C. They are generally absorbed directly into the bloodstream from the small intestine. Most are not stored in significant amounts in the body (with the exception of B₁₂, which is stored in the liver), so daily intake is usually required. Because excess amounts are readily excreted in urine, the risk of toxicity is relatively low. These vitamins often act as coenzymes in metabolic reactions.
Lipid-soluble vitamins include A, D, E, and K. They are absorbed along with dietary fats in the small intestine and require bile salts for solubilization. They are stored in the liver and adipose tissue, which allows the body to maintain reserves over time. However, because they can accumulate, excess intake can lead to toxicity. These vitamins often play roles in gene regulation, antioxidant defense, or blood clotting.
Describe the physiological conditions under which hepcidin levels increase or decrease, and explain the consequences for plasma iron availability.
Hepcidin is a key hormone that regulates systemic iron levels by controlling the activity of ferroportin, the iron-export protein on enterocytes, hepatocytes, and macrophages. Hepcidin levels increase when plasma iron levels are high or during inflammation, particularly in response to cytokines like interleukin-6 (IL-6). Elevated hepcidin causes ferroportin degradation, which reduces iron export from enterocytes and macrophages, leading to decreased plasma iron availability.
Conversely, hepcidin levels decrease during low plasma iron, increased erythropoietic demand (such as after blood loss or during hypoxia), or iron deficiency. Low hepcidin allows ferroportin to remain active, increasing iron absorption from the diet and release of recycled iron from macrophages, thereby raising plasma iron levels to meet the body’s needs.
Which proteolytic zymogens are secreted by the pancreas into the duodenum, and how are proteins digested into absorbable forms in the small intestine? Describe the enzymes involved and the steps of protein breakdown.
The pancreas releases several inactive proteolytic enzymes, or zymogens, into the duodenum to prevent self-digestion. These include trypsinogen, chymotrypsinogen, and procarboxypeptidase. Once in the small intestine, enterokinase (enteropeptidase), a brush border enzyme, activates trypsinogen to trypsin, which then activates the other zymogens. These enzymes break proteins and polypeptides into smaller peptides: trypsin and chymotrypsin cleave internal peptide bonds of polypeptides, while carboxypeptidase removes terminal amino acids from the carboxyl end. Finally, brush border peptidases on enterocytes further digest oligopeptides into dipeptides, tripeptides, and free amino acids, which can be absorbed into the intestinal cells.
Compare the roles of pancreatic amylase and brush border enzymes in carbohydrate digestion. Which substrates do they act on, and what products do they generate?
Pancreatic amylase is secreted by the pancreas into the small intestine and acts in the lumen of the duodenum. Its primary substrates are starch and glycogen that escaped digestion in the mouth. Pancreatic amylase breaks these long polysaccharides into maltose, maltotriose, and α-limit dextrins (branched oligosaccharides), producing smaller chains that are still not fully absorbable.
Brush border enzymes, located on the microvilli of enterocytes, complete carbohydrate digestion. They act on the products of pancreatic amylase:
Maltase converts maltose into two glucose molecules.
Sucrase converts sucrose into glucose and fructose.
Lactase converts lactose into glucose and galactose.
Isomaltase (α-dextrinase) breaks down α-limit dextrins into glucose.
In summary, pancreatic amylase performs the bulk breakdown of polysaccharides in the intestinal lumen, while brush border enzymes complete digestion into monosaccharides, which are the only forms that can be absorbed into the bloodstream.
Compare the roles of chylomicrons, VLDL, IDL, LDL, and HDL in lipid transport. Include which tissues they deliver lipids to and their major cargo.
Chylomicrons are large, triglyceride-rich lipoproteins formed in the enterocytes of the small intestine. They transport dietary triglycerides, cholesterol, and fat-soluble vitamins via the lymphatic system to the bloodstream. Chylomicrons deliver triglycerides primarily to adipose tissue and muscle for storage or energy use. After triglyceride removal, the chylomicron remnants travel to the liver for processing.
Very-low-density lipoproteins (VLDL) are produced by the liver and transport endogenously synthesized triglycerides and cholesterol to peripheral tissues. As VLDL delivers triglycerides via lipoprotein lipase, it becomes smaller and denser, forming intermediate-density lipoproteins (IDL). IDL can either be taken up by the liver or further metabolized into low-density lipoproteins (LDL).
Low-density lipoproteins (LDL) are cholesterol-rich particles derived from VLDL/IDL metabolism. LDL delivers cholesterol to peripheral tissues for membrane synthesis, steroid hormone production, or storage. High LDL levels are associated with increased risk of atherosclerosis.
High-density lipoproteins (HDL) are protein-rich and involved in reverse cholesterol transport. HDL collects excess cholesterol from peripheral tissues and delivers it back to the liver for excretion in bile or reuse. HDL also carries apolipoproteins that serve as cofactors for enzymes involved in lipid metabolism.
Chylomicrons transport dietary triglycerides, VLDL delivers endogenous triglycerides, IDL is an intermediate, LDL delivers cholesterol to tissues, and HDL removes cholesterol from tissues back to the liver, maintaining lipid homeostasis.
Differentiate between short-term and long-term regulators of appetite. Provide examples of each and explain how they signal the brain.
Appetite is regulated by both short-term and long-term signals, which help the body balance immediate energy intake with overall energy stores.
Short-term regulators control meal-to-meal hunger and satiety. They respond to the current state of nutrient availability in the gut and blood. Examples include:
GLP-1 (glucagon-like peptide-1): Secreted by intestinal L-cells in response to food. Slows gastric emptying and signals satiety to the hypothalamus.
Ghrelin: Secreted by the stomach during fasting; stimulates hunger by acting on the hypothalamus.
Cholecystokinin (CCK): Secreted by the small intestine in response to fats and proteins; promotes satiety.
Long-term regulators communicate the body’s energy stores to the brain over days to months, helping regulate body weight and overall appetite. Examples include:
Leptin: Secreted continuously by adipose tissue; higher fat stores → higher leptin. Signals the hypothalamus to suppress appetite and increase energy expenditure. Low leptin (during fasting or weight loss) increases hunger.
Insulin: Baseline insulin levels reflect overall energy intake and fat mass. Chronically elevated insulin can signal adequate energy stores, reducing appetite.
Mechanism of signaling: Both short-term and long-term regulators act primarily on the hypothalamus, especially the arcuate nucleus, influencing neurons that either stimulate or inhibit feeding behavior based on energy availability.
hort-term regulators respond to immediate nutrient intake, controlling hunger at meals, while long-term regulators provide the brain with information about body energy stores, adjusting appetite and energy expenditure over time.
Compare and contrast the roles of enterocytes, hepatocytes, and macrophages in maintaining iron homeostasis.
Enterocytes, located in the duodenum, are responsible for absorbing dietary iron. Non-heme iron is reduced from Fe³⁺ to Fe²⁺ before uptake, and once inside the enterocyte, iron can either be stored temporarily as ferritin or exported into the bloodstream via ferroportin. Hepcidin regulates this export by promoting ferroportin degradation when plasma iron is high.
Macrophages, primarily in the spleen and liver, are critical for recycling iron from senescent or damaged erythrocytes. They phagocytose old red blood cells, recover the iron from hemoglobin, and either store it as ferritin or release it into plasma via ferroportin, also under hepcidin regulation.
Hepatocytes, in the liver, act as the primary iron storage site. They store excess iron as ferritin or, when overloaded, as hemosiderin. Hepatocytes also produce hepcidin, the hormone that regulates systemic iron levels by controlling iron export from enterocytes and macrophages.
Enterocytes manage dietary iron absorption, hepatocytes manage storage and hormonal control, and macrophages handle recycling from red blood cells. Together, they ensure that plasma iron remains sufficient for erythropoiesis and other metabolic needs while preventing iron overload.
Describe what happens during transamination, including the molecules involved and the outcome for both substrates.
During transamination, an amino group (–NH₂) is transferred from an amino acid to α-ketoglutarate in a reaction catalyzed by a transaminase (aminotransferase) enzyme. As a result, the original amino acid is converted into its corresponding keto acid, and α-ketoglutarate becomes glutamate.
This process moves nitrogen without producing free ammonia, allowing amino acids to be safely prepared for energy metabolism while conserving nitrogen in the body.
Differentiate between glycogenesis, glycogenolysis, and gluconeogenesis, including their substrates, products, and role in maintaining blood glucose levels.
Glycogenesis is the process of synthesizing glycogen from glucose. The substrate is glucose (as glucose-6-phosphate), and the product is glycogen, which is stored primarily in the liver and skeletal muscle. Glycogenesis occurs after a meal, when blood glucose levels are high, and its main role is to store excess glucose for later use, helping maintain blood glucose homeostasis.
Glycogenolysis is the breakdown of glycogen into glucose. The substrate is glycogen, and the product is glucose-1-phosphate, which is converted to glucose-6-phosphate; in the liver, this can be released as free glucose into the blood. Glycogenolysis occurs during fasting or between meals, providing a rapid source of glucose to maintain blood glucose levels.
Gluconeogenesis is the synthesis of new glucose from non-carbohydrate precursors, such as lactate, glycerol, and certain amino acids. The product is glucose, which is released into the bloodstream. Gluconeogenesis occurs primarily in the liver during prolonged fasting, low-carbohydrate intake, or intense exercise, ensuring a continuous supply of glucose for tissues that rely on it, such as the brain and red blood cells.
Glycogenesis stores glucose, glycogenolysis mobilizes stored glucose quickly, and gluconeogenesis generates new glucose from non-carbohydrate sources; together, these pathways maintain blood glucose homeostasis under varying dietary and metabolic conditions.
Explain how fat metabolism supports energy needs during fasting, prolonged exercise, or low-carbohydrate intake. Include the role of ketogenesis and gluconeogenesis.
During fasting, prolonged exercise, or low-carbohydrate intake, the body relies more heavily on fat metabolism to meet energy demands and spare glucose for tissues that depend on it, such as the brain and red blood cells.
Lipolysis in adipose tissue releases triglycerides as glycerol and fatty acids. Fatty acids are transported to the liver, muscle, and other tissues for energy. In the mitochondria, fatty acids undergo β-oxidation, producing acetyl-CoA, which enters the citric acid cycle to generate ATP.
When glucose is scarce and acetyl-CoA accumulates in the liver, excess acetyl-CoA is converted into ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) in a process called ketogenesis. Ketone bodies are water-soluble and can be used as an alternative energy source by the brain, heart, and skeletal muscle during prolonged fasting or carbohydrate restriction.
Meanwhile, glycerol released from triglycerides can be converted to dihydroxyacetone phosphate (DHAP) and used in gluconeogenesis to produce new glucose in the liver, maintaining blood glucose levels for tissues that cannot use fatty acids.
Fat metabolism supports energy needs by providing ATP from β-oxidation, generating ketone bodies as an alternative fuel for glucose-dependent tissues, and supplying glycerol for gluconeogenesis, ensuring energy homeostasis during fasting, exercise, or low-carbohydrate intake.
Explain how leptin communicates information about body fat stores to the hypothalamus. What happens to appetite and energy expenditure when leptin levels are low?
Leptin is a hormone secreted primarily by adipose (fat) tissue in proportion to the amount of stored fat. It communicates the body’s energy reserves to the hypothalamus, especially the arcuate nucleus, by binding to leptin receptors on neurons that regulate appetite and energy expenditure.
When fat stores are sufficient or high: Leptin levels are elevated. It inhibits appetite-stimulating neurons (NPY/AgRP) and activates satiety-promoting neurons (POMC/CART), resulting in reduced hunger and increased energy expenditure.
When fat stores are low (e.g., during fasting or weight loss): Leptin levels fall. The hypothalamus senses this decrease, leading to activation of hunger signals and reduction in energy expenditure as the body attempts to conserve energy and restore fat stores.
Leptin provides a long-term signal of energy sufficiency. Low leptin levels trigger increased appetite and energy conservation, whereas high leptin levels suppress appetite and promote energy use, helping maintain body weight homeostasis.