Metabolism is the collection of chemical reactions that keep cells alive. It includes pathways that break down nutrients for energy (catabolism) and pathways that build needed molecules (anabolism). This note explains major metabolic pathways in simple language—no chemical structures—so D.Pharmacy students can grasp the core ideas and related diseases.
ACTUAL NOTES:
Metabolism: Carbohydrates, Lipids, Proteins and Biological Oxidation
Metabolism is the collection of chemical reactions that keep cells alive. It includes pathways that break down nutrients for energy (catabolism) and pathways that build needed molecules (anabolism).
Metabolism of Carbohydrates
Glycolysis (Brief overview)
Glycolysis is the step-by-step breakdown of glucose to produce small amounts of energy and two molecules of pyruvate. It occurs in the cytoplasm and does not require oxygen. Key points: glucose → intermediate steps → 2 ATP (net) + 2 NADH + 2 pyruvate. Glycolysis supplies quick energy and intermediates for other pathways.
TCA Cycle (Krebs or Citric Acid Cycle)
The TCA cycle happens in mitochondria and processes the product of glycolysis (acetyl-CoA) to produce high-energy carriers (NADH, FADH2) and a small amount of ATP. These carriers feed the electron transport chain to make most of the cell’s ATP. The TCA cycle also supplies building blocks for biosynthesis.
Glycogen Metabolism
Glycogen is the storage form of glucose in liver and muscle. Two main processes control glycogen levels:
- Glycogenesis: Building glycogen when glucose is abundant (stored for later).
- Glycogenolysis: Breaking down glycogen to release glucose when the body needs energy.
The liver helps maintain blood glucose for other organs; muscle glycogen fuels local muscle activity.
Regulation of Blood Glucose
Blood glucose is tightly regulated by hormones:
- Insulin: Released after meals; promotes glucose uptake, glycogenesis, and lowers blood glucose.
- Glucagon: Released during fasting; stimulates glycogenolysis and gluconeogenesis to raise blood glucose.
- Adrenaline and cortisol: Raise blood glucose during stress.
Diseases from Carbohydrate Metabolism Abnormalities
- Diabetes mellitus: Insulin deficiency or resistance causes high blood glucose and long-term complications.
- Glycogen storage diseases: Defects in enzymes of glycogen metabolism lead to abnormal storage and low blood sugar.
- Lactic acidosis: Excess anaerobic glycolysis (build-up of lactate) in hypoxia or mitochondrial defects.
Metabolism of Lipids
Lipolysis
Stored triglycerides (in fat tissue) are broken down into glycerol and free fatty acids when energy is needed. Hormones like adrenaline and glucagon activate lipolysis.
β-Oxidation of Fatty Acids (General idea)
Fatty acids (e.g., palmitic acid) are transported into mitochondria and shortened stepwise by β-oxidation to produce acetyl-CoA, NADH and FADH2. Each cycle removes two-carbon units as acetyl-CoA, which then enters the TCA cycle for energy production.
Ketogenesis and Ketolysis
When carbohydrate supply is low (fasting, uncontrolled diabetes), excess acetyl-CoA in liver is converted into ketone bodies (ketogenesis). Ketone bodies provide energy to brain and muscle during starvation. Ketolysis is the use of ketones by other tissues for energy.
Diseases from Lipid Metabolism Abnormalities
- Ketoacidosis: In uncontrolled diabetes, high ketone levels make blood acidic — a medical emergency.
- Fatty liver (hepatic steatosis): Excess fat accumulation in the liver due to imbalanced lipid metabolism or alcohol.
- Hypercholesterolemia / Atherosclerosis: Elevated blood cholesterol and LDL lead to plaque formation and cardiovascular disease.
Metabolism of Amino Acids (Proteins)
General Reactions and Significance
Amino acids are used to build proteins, make neurotransmitters and for energy when needed. Their metabolism includes major reactions like transamination, deamination, decarboxylation and entry into central pathways.
Transamination
Transamination transfers an amino group from one amino acid to a keto acid, forming a new amino acid and new keto acid. This process is important for synthesizing non-essential amino acids and recycling nitrogen.
Deamination
Deamination removes the amino group to produce ammonia (NH₃) and a corresponding keto acid that can enter energy metabolism. Ammonia is toxic and must be converted to a less toxic form.
Urea Cycle
The urea cycle (in the liver) converts toxic ammonia into urea, which is excreted by the kidneys. This cycle is essential to prevent ammonia accumulation.
Decarboxylation
Decarboxylation removes the carboxyl group from amino acids to form important biologically active amines (e.g., conversion of glutamate to GABA).
Diseases from Amino Acid Metabolism Defects
- Disorders of ammonia metabolism: Urea cycle defects cause hyperammonemia leading to neurological damage.
- Phenylketonuria (PKU): Deficiency of phenylalanine hydroxylase leads to accumulation of phenylalanine causing developmental delay; early dietary management prevents damage.
- Alkaptonuria: Defect in tyrosine degradation; homogentisic acid accumulates causing dark urine and connective tissue pigmentation.
- Jaundice: Although mainly a bilirubin/liver disorder, impaired protein metabolism and liver dysfunction often coexist and aggravate metabolic problems.
Biological Oxidation: Electron Transport Chain and Oxidative Phosphorylation
Electron Transport Chain (ETC) — Simple View
High-energy carriers (NADH, FADH2) produced in glycolysis, β-oxidation and TCA deliver electrons to the electron transport chain in the inner mitochondrial membrane. The ETC is a series of protein complexes that pass electrons from one complex to the next.
Oxidative Phosphorylation
As electrons move through the ETC, energy is released and used to pump protons (H⁺) across the inner mitochondrial membrane, creating a proton gradient. ATP synthase uses this proton flow back into the matrix to synthesize ATP from ADP and inorganic phosphate. This coupling of electron transfer to ATP synthesis is called oxidative phosphorylation and generates the majority of cellular ATP.
Why ETC and Oxidative Phosphorylation Matter
- They produce most of the cell’s ATP — the energy currency needed for all biological work.
- Dysfunction (e.g., mitochondrial diseases, toxins like cyanide) severely reduces ATP production and causes energy failure.
