Cell Metabolism

Food undergoes a transformative journey within our bodies, requiring both mechanical and chemical processes to convert it into absorbable forms for energy and building blocks. This complex process is driven by specialized enzymes that facilitate chemical digestion.  In this laboratory exploration, you will study posters detailing key metabolic pathways in chemical digestion such as gluconeogenesis, glycogenesis, glycogenolysis, proteolysis, lipolysis, and lipogenesis to understand how our bodies manage energy storage and utilization from different biomolecules.

To comprehend this biological marvel, let’s first establish some foundational vocabulary:

• Digestion: The intricate process of breaking down food into nutrients capable of transport into the body.
• Digestive enzymes: Specialized proteins synthesized within specific cells, deployed into the digestive tract to expedite the extracellular breakdown of biological nutrients, including proteins, carbohydrates, and lipids.
• Mechanical digestion: The physical manipulation of food, encompassing actions like chewing, chyme mixing, and peristalsis.

Metabolism is the sum of all chemical reactions in the human body and is classified into two categories: catabolic and anabolic. A metabolic pathway is a series of biochemical reactions that transform molecules step by step through metabolic intermediates into a final product or products.

Anabolic pathways require energy to build complex molecules from simpler ones, while catabolic pathways break down complex molecules into simpler components, releasing energy. In other words, catabolic reactions break down large molecules, whereas anabolic reactions synthesize larger molecules from smaller building blocks.

For nutrients from ingested food to be absorbed, digestion must first occur, breaking down into easily absorbable units.  This process involves both mechanical actions, such as chewing and peristalsis, and chemical processes catalyzed by digestive enzymes.

Digestive enzymes are synthesized within specialized cells and released into the digestive tract, where they accelerate the extracellular breakdown of nutrients in food and fluids. The products of chemical digestion are then absorbed into the bloodstream or lymphatic vessels of the small intestine, transported to cells throughout the body, and utilized in intracellular metabolism.  Key metabolic processes include aerobic respiration, glycolysis, lipolysis, and protein synthesis.

The Small Intestine: The absorptive surface of the small intestine. (Figure by OpenStax is used under a Creative Commons Attribution license.)

Extracellular digestion depends on enzyme-catalyzed hydrolysis, in which hydrolytic enzymes, or hydrolases, add water to break down larger food molecules into their individual building blocks.

Proteins  + H₂0  + enzyme    ⟶   amino acids  +  enzyme

Fats + H₂0 + enzyme ⟶  fatty acids + glycerol (or monoglyceride) + enzyme

Carbohydrates + H₂0 +  enzyme  ⟶   monosaccharides +  enzyme

Each of these reactions within the body depends on the presence and activity of specific hydrolytic enzymes.  Factors that affect enzyme activity include pH and temperature.

Temperature and pH are tightly regulated within narrow ranges in the body to ensure optimal conditions for enzymatic activity.  These organic molecules are essential in maintaining the body’s metabolic balance.  During the absorptive state (3-5 after eating), or fed, state, glucose serves as the primary energy source, with minimal use of absorbed fats and amino acids.  In contrast, the postabsorptive (8-12 after a meal), or fasting, state prompts the body to rely on its energy reserves to fulfill its energy demands.

Proteins

Proteins, also known as polypeptides, consist of amino acids – monomers covalently bonded together by peptide bonds.  These amino acids share a common chemical backbone but differ in their R groups, or side chains, which determine their classification as polar, charged, or nonpolar.  While all proteins exhibit hydrophilic properties (affinity for water), the degree of hydrophilicity varies.  Some proteins feature a higher proportion of nonpolar side chains, rendering them less hydrophilic compared to others.

Amino Acid Structure. (Figure by OpenStax is used under a Creative Commons Attribution license.)

Proteins possess complex structures, transitioning from a primary to secondary, tertiary, and often quaternary structure to fulfill specific functions.  Maintaining the optimal temperature is crucial for preserving their structure and ensuring proper enzyme activity.

Protein Structure: Primary, Secondary, Tertiary, and Quaternary Structure. (Figure by OpenStax is used under a Creative Commons Attribution license.)

The process of protein digestion begins in the stomach with the enzyme pepsin.  Typically, inactive when the stomach is empty, pepsin becomes activated upon food entry.  Produced by the chief cells of the stomach as the inactive form, pepsinogen.  Pepsinogen is activated into pepsin by stomach acid and active pepsin cleavage.  Once active, pepsin catalyzes the hydrolysis of proteins into smaller peptides.  Pepsin functions most effectively in the stomach’s acidic environment, with an optimal pH of 2. However, it denatures as chyme transitions into the small intestine, where the pH rises to around 9.

Continuing the hydrolysis of proteins into peptides, the duodenum of the small intestine hosts pancreatic enzymes such as trypsin, chymotrypsin, and carboxypeptidase.  These enzymes further break down peptides into amino acids.  Aminopeptidases and dipeptidases, enzymes produced in the brush border of the small intestine, play vital roles in this process by further degrading peptides into individual amino acids.

After digestion, amino acids are absorbed into the capillaries of the small intestine and transported via the bloodstream to the liver through the hepatic portal vein.

Protein Metabolism

The breakdown process of proteins into amino acids is called proteolysis, while the synthesis of proteins is referred to as proteogenesis.

Carbohydrates

Carbohydrates, also known as polysaccharides, consist of polymers of simple sugars, or monomers, linked together by glyosidic bonds.  Glucose, often emphasized in physiology courses, stands out as the primary substrate for aerobic respiration and is also involved in fermentation.  While most carbohydrates contribute to energy metabolism, some serve in specialized cell coatings.

Monosaccharides: The five monosaccharides important in the human body. (Figure by OpenStax is used under a Creative Commons Attribution license.)

The abundant hydroxyl, ketone, and aldehyde side groups on each simple sugars render all carbohydrates hydrophilic.

The breakdown of carbohydrates, particularly starch (from our diet), begins with the enzyme amylase.  Salivary amylase produced by the salivary glands, initiates carbohydrate digestion in the mouth, while pancreatic amylase, secreted by the pancreas, continues the process in the duodenum. As carbohydrates are broken down into simple sugars, they become absorbable.  As a result, absorption of these sugars occurs in both the mouth and duodenum. It’s important to remember that carbohydrates are not inherently “bad”; rather, like any nutrient, excessive consumption (of any nutrient) can lead to negative effects.  However, carbohydrates play a vital role in maintaining the body’s homeostasis.

Polysaccharides: Three important polysaccharides. (Figure by OpenStax is used under a Creative Commons Attribution license.)

Amylose, a component of starch, acts as the substrate for the enzyme amylase, which catalyzes its hydrolysis into maltose.  Maltose, a disaccharide, is further breakdown into two glucose molecules, or monosaccharides, by the enzyme maltase, primarily located in the brush border of the small intestine.  These monosaccharides are then absorbed into the bloodstream through the hepatic portal vein, ultimately reaching the liver for metabolism.  In the liver, glucose can be either be converted into ATP for cellular energy or stored as glycogen, a polysaccharide.

Carbohydrate Metabolism

The catabolic process of converting glucose into ATP is known as glycolysis, while the anabolic process of forming glycogen from glucose is called glycogenesis.  In contrast, glycogenolysis involves the breaks down glycogen into glucose.  Gluconeogenesis, a process done by the liver (and to a minor degree, by some cells of the renal system), refers to the synthesis of new glucose molecules from alternative sources, such as proteins or lipids.

Pancreatic hormones, particularly insulin and glucagon, are important in regulating fuel metabolism.  Insulin promotes glucose uptake into cells, stimulates glycogenesis, and inhibits glycogenolysis and gluconeogenesis, effectively lowering blood glucose levels. On the other hand, glucagon stimulates glucose production, inhibits glycogenesis, and activates both glycogenolysis and gluconeogenesis, leading to an increase of blood glucose levels.

Lipids

Lipids consist of fats and fatty acids, serving as their monomers, bonded together via simple covalent bonds, often in the form of ester bonds.  Importantly, this group is predominantly hydrophobic, distinguishing it from other biomolecules.  Within human physiology, steroids, phospholipids and eicosanoids stand out, playing significant roles in cell signaling.  Moreover, they are frequently discussed in the context of cell membranes and lipid storage, particularly as triglycerides within adipocytes.

Triglycerides: These are composed of glycerol attached to three fatty acids. (Figure by OpenStax is used under a Creative Commons Attribution license.)

Because lipids are insoluble in water, they must first undergo emulsification, the breakdown fat globules down into smaller droplets with the help of bile, before they can be used for energy when other energy sources are running low. Bile salts, produced by the liver, stored in the gallbladder, and released into the small intestine as needed, play a key role in this process by breaking large lipid molecules, primarily triglycerides, into smaller droplets. These droplets form micelles, which increase the surface area for lipase enzymes to act on, facilitating the digestion and absorption of fatty acids, small fats, and fat-soluble vitamins (A, D, E, and K).

Lipids Metabolism

The digestion of lipids follows the same general process of carbohydrates and proteins, where larger molecules are broken down by enzymes into smaller molecules before absorption.  However, because lipids are insoluble in water (hydrophobic), their absorption mechanism differs.  Triglycerides are primarily broken down into fatty acids and monoglycerides by pancreatic lipases, while bile salts emulsify fat droplets, increasing their surface area for enzymatic action.  The resulting digestion products (fatty acids and monoglycerides) enter epithelial cells of the small intestine by simple diffusion, where they are reassembled into triglycerides.  These are often packaged into chylomicrons and transported through the lymphatic system for distribution throughout the body.

In summary, the body tightly regulates blood glucose levels within a narrow range, typically between 70 to 130 mg/dL, to ensure a steady fuel supply for the brain, maintaining homeostasis.  During the absorptive state, or fed state, the body uses glucose for immediate energy and stores excess nutrients for future use. When blood glucose levels rise, the pancreas releases insulin, promoting a shift from catabolic to anabolic processes.  This hormonal response stimulates: glycogenesis, lipogenesis, and protein synthesis.

During the postabsorptive state, the gastrointestinal tract empties, and the body relies on stored energy.  As blood glucose levels drop, the pancreas releases glucagon, shifting the body from anabolic to catabolic processes, including: glycogenolysis, lipolysis, proteolysis and gluconeogenesis.

Additionally, the body stores energy by synthesizing fats (in adipose tissue) and proteins, ensuring long-term metabolic balance.

The Process of Digestion

Digestion begins in the oral cavity, where the mechanical breakdown of food occurs through mastication or chewing.  Coordinated movements of the teeth and tongue break food into smaller pieces while saliva mixes with it, forming a bolus, a soft cohesive mass that is lubricated and contains enzymes to aid digestion.  The tongue then pushes the bolus into the pharynx, where the pathways for food and air separate.

From the pharynx, the bolus moves down the esophagus through peristalsis, a rhythmic wave of smooth muscle contractions, until it reaches the stomach.  Several factors influence peristalsis, including:

• The strength and duration of smooth muscle contractions in the gastrointestinal (GI) tract.
• Neuromuscular signaling between the GI tract and smooth muscle.
• The composition of chyme and hydration levels.

Together, these factors regulate the efficiency of digestion and ensure the smooth transit of food through the digestive system. Throughout this process, the GI system’s regulatory mechanisms continuously optimize digestion and absorption while efficiently eliminating waste.

Peristalsis: A process that moves food through the digestive tract by alternating contractions and relaxations of the muscles, creating wave movements. (Figure by OpenStax is used under a Creative Commons Attribution license.)

The Role of the Stomach and Intestines

The stomach plays a crucial role in digestion by vigorously mixing food with gastric juices, breaking it down into a highly acidic mixture known as chyme.  This digested material then enters the small intestine, where nutrient absorption primarily occurs in the duodenum.

Next, the large intestine absorbs excess water, and the remaining waste moves toward the rectum.  Finally, the waste is expelled through the anus, which consists of both involuntary and voluntary muscles.  The voluntary muscles allow for conscious control over bowel movements, enabling individuals to regulate when they need to use the restroom.

The Digestive Processes. (Figure by OpenStax is used under a Creative Commons Attribution license.)

Adapted from Human Physiology Lab Manual by Jim Blevins, Melaney Farr, and Arleen Sawitzke, Salt Lake Community College.