Summary
Highlights
Dr. Mike introduces an overview of metabolism, focusing on key terms frequently assessed in biochemistry and metabolism exams. These terms include glycolysis, glycogenesis, glycogenolysis, gluconeogenesis, Krebs cycle, electron transport chain, lipogenesis, lipolysis, ketogenesis, and ketolysis. The goal is to cover these concepts concisely.
The explanation starts with ingesting a cheeseburger, which contains carbohydrates, proteins, and triglycerides (fats). Carbohydrates are composed of carbons, hydrogens, and oxygens in roughly equivalent ratios. Proteins add nitrogen to these elements. Triglycerides have disproportionately more carbons and hydrogens compared to oxygens, making them hydrophobic. Digestion begins in the mouth with salivary amylase breaking carbs into glucose. In the stomach, hydrochloric acid and pepsin break down proteins into amino acids. In the small intestines, bile and lipases break down fats into glycerol and fatty acids.
Glucose and amino acids are absorbed into the bloodstream via the portal system, leading to the liver. Glycerol and fatty acids are absorbed into the lymphatic system before eventually reaching the liver. The liver is a central organ for processing all these micronutrients.
When glucose enters the liver, it can be stored as glycogen through a process called glycogenesis (genesis meaning beginning of glycogen). Conversely, glycogen can be broken down into glucose through glycogenolysis (lysis meaning to split apart). To utilize free glucose for energy (ATP), it's converted into pyruvate via glycolysis. Pyruvate then enters the mitochondria.
Inside the mitochondria, pyruvate is converted into acetyl-CoA. Acetyl-CoA, with the help of oxaloacetate, then enters the Krebs cycle (also known as the tricarboxylic acid cycle or citric acid cycle). The Krebs cycle's main purpose is to produce NADH and FADH2. These molecules carry hydrogen ions and electrons to the electron transport chain, located in the inner mitochondrial membrane. The electron transport chain passes electrons along, pumping hydrogen ions into the intermembrane space, creating a concentration gradient. These hydrogen ions then flow back through ATP synthase, generating large amounts of ATP. This process requires oxygen and is called oxidative phosphorylation.
In situations with insufficient oxygen (e.g., intense exercise), the electron transport chain backs up, leading to a build-up of pyruvate. Pyruvate is then converted into lactate. Historically, it was believed to be lactic acid, causing a burning sensation due to hydrogen ions. However, current understanding suggests lactate is directly produced and can even buffer hydrogen ions. Remarkably, lactate can be reversibly converted back to pyruvate when oxygen becomes available, allowing it to re-enter the aerobic pathway.
Excess amino acids are not typically stored; they are deaminated and excreted as urea or synthesized into proteins. However, amino acids can also enter glycolysis or the Krebs cycle to produce energy. Glycerol can enter glycolysis, and fatty acids can be converted to acetyl-CoA and enter the Krebs cycle. These alternative fuel sources are predominantly used when glucose is scarce.
When glucose levels are low, oxaloacetate can be diverted from the Krebs cycle to produce new glucose from non-carbohydrate sources like amino acids and glycerol a process called gluconeogenesis (new glucose beginning). This depletion of oxaloacetate leads to an accumulation of acetyl-CoA, which then combines to form ketones (e.g., beta-hydroxybutyrate). This process is known as ketogenesis. Ketones can leave the liver, cross the blood-brain barrier, and be converted back into acetyl-CoA in the brain to serve as an energy source, a process called ketolysis.
When there is an excess of glycerol and fatty acids, they can recombine to form triglycerides and be stored in the liver or adipose tissue. This process is called lipogenesis (formation of lipids). The breakdown of these stored triglycerides back into glycerol and fatty acids for energy is called lipolysis (splitting apart lipids).