METABOLISM: A TEACHER’S COMPREHENSIVE GUIDE
Welcome, future pharmacists and healthcare professionals!
Metabolism consists of a series of reactions occurring within cells of living organisms to sustain life. It is the total of anabolism and catabolism.
- Anabolism: The biochemical process in metabolism where simple molecules combine to generate complex molecules.
- Catabolism: The set of metabolic pathways that break down molecules into smaller units that are either oxidised to release energy or used in other anabolic reactions.
Dpharmguru’s exam insights:
In my years of teaching biochemistry, I have observed that students often get confused between anabolism and catabolism. Remember: Anabolism = “building up” (requires energy), Catabolism = “breaking down” (releases energy). This is a fundamental concept that appears in almost every biochemistry exam!
METABOLISM OF CARBOHYDRATES
Biochemical processes involved in synthesis, breakdown, and interconversion of carbohydrates in living organisms are collectively called carbohydrate metabolism. Glucose is the essential molecule of carbohydrate metabolism which participates in various metabolic pathways. Insulin is the primary metabolic hormone synthesised in pancreas and regulates blood glucose level.
1. Glycolysis (Embden-Meyerhof Pathway)
Glycolysis is an important pathway of carbohydrate metabolism and occurs in the cytosol of a living cell. In glycolysis (under aerobic conditions), one mole of glucose yields two moles of pyruvate, ATP, and NADH; while under anaerobic conditions one mole of glucose yields two moles of lactates and ATP.
Phases of Glycolysis
- Energy Investment Phase: Requires 2 ATP molecules for phosphorylation. Glucose is converted to glucose-6-phosphate, then to fructose-6-phosphate, and finally to fructose-1,6-bisphosphate.
- Splitting Phase: Fructose-1,6-bisphosphate is cleaved into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
- Energy Generation Phase: One glucose molecule yields 4 ATP molecules. Under anaerobic conditions, pyruvate is reduced to lactate.
Energetics of Glycolysis
Net gain in glycolysis is 2 ATP, 2 pyruvate, and 2 NADH molecules. Under aerobic conditions, net ATP produced is 8. Under anaerobic conditions, net ATP produced is 2.
Dpharmguru’s exam insights:
A common exam question is: “How many ATP are produced in glycolysis?” Remember: Under aerobic conditions, 8 ATP; under anaerobic conditions, 2 ATP. Also, glycolysis occurs in the cytosol—this is frequently tested!
2. Tricarboxylic Acid (TCA) Cycle
The TCA cycle (or citric acid cycle or Krebs cycle) occurs in mitochondria when acetyl CoA enters into mitochondria. It is an amphibolic pathway as its intermediates are utilised in many anabolic pathways.
Steps of TCA Cycle
- Formation of Citrate from acetyl-CoA and oxaloacetate
- Isomerisation of Citrate to Isocitrate
- Formation of α-Ketoglutarate
- Conversion of α-Ketoglutarate to Succinyl CoA
- Formation of Succinate
- Conversion of Succinate to Fumarate
- Formation of Malate
- Conversion of Malate to Oxaloacetate
Energetics of TCA Cycle
One molecule of acetyl CoA produces 3 NADH, 1 FADH₂, and 1 GTP. On oxidation, 12 ATP are produced per acetyl CoA. 24 ATP are produced on aerobic oxidation of glucose.
3. Glycogen Metabolism
Glycogenesis
Glycogenesis is glycogen synthesis from glucose. It occurs in cytosol with the help of ATP and UTP. Glucose is converted to glucose-6-phosphate, then to glucose-1-phosphate, and finally to UDP-glucose. Glycogen synthase forms α-1,4-glycosidic linkages.
Glycogenolysis
Glycogenolysis involves conversion of stored glycogen in liver and muscles to glucose-1-phosphate and then to glucose-6-phosphate, in the presence of glucagon and epinephrine.
4. Regulation of Blood Glucose Level
Blood glucose level is regulated by negative feedback pathways by two hormones: insulin and glucagon. Both are secreted by islet cells of the pancreas.
- Insulin: Secreted by β-cells. Lowers blood glucose by increasing glucose uptake, glycogen formation, and fat synthesis.
- Glucagon: Secreted by α-cells. Raises blood glucose by promoting glycogen breakdown and glucose release from the liver.
DISEASES RELATED TO ABNORMAL METABOLISM OF CARBOHYDRATES
1. Diabetes Mellitus (DM)
Diabetes mellitus is a metabolic disorder characterised by chronic hyperglycaemia resulting from defects in insulin secretion, insulin action, or both.
- Type 1 DM: Destruction of β-cells; insulin required for survival.
- Type 2 DM: Disorders of insulin action and secretion; relative insulin deficiency.
Symptoms: Polydipsia, polyuria, polyphagia, weight loss, fatigue, blurred vision, and slow wound healing.
Treatment: Diet control, physical activity, insulin therapy, and oral hypoglycaemic agents (sulphonylureas, biguanides, thiazolidinediones, α-glucosidase inhibitors).
2. Galactosaemia
Galactosaemia is a genetic disorder where the ability to metabolise galactose sugar is hampered due to absence of Galactose-1-Phosphate Uridylyltransferase (GALT) enzyme.
Treatment: Low-galactose diet. Avoid milk and foods containing lactose or galactose.
3. Hereditary Fructose Intolerance
A condition where the ability to digest fructose is hampered due to deficiency of fructose-1-phosphate aldolase enzyme.
Treatment: Strictly controlled diet eliminating fructose-, sucrose-, and sorbitol-containing foods.
4. Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
An X-linked genetic disorder causing premature breakdown of RBCs (haemolysis).
Treatment: Remove triggering factors (drugs or infections). Oxygen therapy and blood transfusion in severe cases.
Dpharmguru’s exam insights:
Remember: G6PD deficiency is X-linked and mostly affects males. Drugs like primaquine and sulphonamides can trigger haemolysis in G6PD-deficient patients. This is a common exam question!
METABOLISM OF LIPIDS
1. β-Oxidation of Fatty Acids
By β-oxidation, fatty acids are broken down to smaller units of acyl-CoA molecules in mitochondria to produce acetyl-CoA.
Stages:
- Activation of fatty acids in the cytosol
- Transport of activated fatty acids into mitochondria (carnitine shuttle)
- β-oxidation of fatty acids in the mitochondrial matrix
Energetics of Palmitic Acid Oxidation
Complete oxidation of palmitic acid (16 carbon) yields 129 ATP molecules.
2. Biosynthesis of Palmitic Acid
De novo synthesis of fatty acid takes place in cytosol with precursor acetyl CoA and ends by forming palmitic acid.
Overall reaction:
8 Acetyl CoA + 7 ATP + 14 NADPH + 14 H⁺ → Palmitate + 8 CoA + 7 ADP + 14 NADP⁺
3. Metabolism of Ketone Bodies
Ketone bodies (acetoacetic acid, β-hydroxybutyric acid, and acetone) serve as a circulating energy source for tissues during prolonged fasting or starvation.
Diseases Related to Abnormal Metabolism of Lipids
1. Ketoacidosis
When insulin secretion is decreased, ketone bodies accumulate in the bloodstream resulting in ketoacidosis. Types include alcoholic ketoacidosis, diabetic ketoacidosis, and starvation ketoacidosis.
2. Fatty Liver
Fatty liver (hepatic steatosis) is excessive fat accumulation in the liver accounting for more than 5-10% of liver’s weight.
Causes: Alcoholism, obesity, hyperlipidemia, diabetes, and rapid weight loss.
3. Hypercholesterolemia
A condition of high cholesterol levels in the blood. Treatment includes dietary modifications, lifestyle changes, and therapeutic agents (statins).
METABOLISM OF AMINO ACIDS (PROTEINS)
1. Transamination
Transamination is the transfer of an amine group from one molecule to another in the presence of transaminase enzymes. Pyridoxal Phosphate (PLP) derived from vitamin B₆ is the coenzyme required.
2. Deamination
Removal of amino group from amino acid as NH₃ is called deamination. The ammonia produced participates in urea synthesis.
3. Decarboxylation
Decarboxylation is a catabolic pathway in which CO₂ is removed from the carboxyl group of amino acids. Pyridoxal Phosphate (PLP) is the coenzyme required.
4. Urea Cycle
Urea synthesis occurs in liver and is the final product of amino acid or protein metabolism. It partly occurs in mitochondria and partly in cytoplasm.
Steps:
- Synthesis of Carbamoyl Phosphate
- Synthesis of Citrulline
- Synthesis of Arginosuccinate
- Cleavage of Arginosuccinate
- Formation of Urea
Dpharmguru’s exam insights:
A common exam question is: “Which organ synthesizes urea?” The answer is the liver. Also, the urea cycle was discovered by Hans Krebs in 1932. This is frequently tested!
Diseases Related to Abnormal Metabolism of Amino Acids
1. Phenylketonuria (PKU)
PKU is a genetic disorder related to the inability to convert phenylalanine to tyrosine due to defective phenylalanine hydroxylase enzyme.
Treatment: Low phenylalanine diet. In severe cases, 5-hydroxytryptophan and dopa are prescribed.
2. Alkaptonuria (Black Urine Disease)
A rare genetic disorder involving deficiency of homogentisate-1,2-dioxygenase (HGD) enzyme, causing accumulation of homogentisic acid.
Symptoms: Urine turns dark (black-brown) after exposure to air. Long-term deposition causes ochronosis (black pigmentation of tissues).
3. Jaundice
Jaundice refers to yellow colouration of the skin, mucosa, and sclera due to accumulation of bilirubin.
- Pre-hepatic Jaundice: Due to increased haemolysis of RBCs.
- Hepatic Jaundice: Due to liver dysfunction.
- Post-hepatic Jaundice: Due to obstruction in bile flow.
- Neonatal Jaundice: Occurs in newborns due to immature liver.
BIOLOGICAL OXIDATION
Electron Transport Chain (ETC)
The electron transport chain is the final common pathway of biological oxidation. It is located in the inner membrane of the mitochondria.
Components of ETC:
- Nicotinamide Nucleotides (NAD⁺)
- Flavoproteins (NADH dehydrogenase)
- Iron-Sulphur Proteins
- Coenzyme Q
- Cytochromes
Oxidative Phosphorylation
Oxidative phosphorylation is the oxidation of substrate by oxygen and phosphorylation of ADP to ATP via Electron Transport Chain.
Chemiosmotic Hypothesis: Proposed by Peter Mitchell. Explains transport of electrons through ETC which is utilised for generating ATP from ADP + Pi.
Dpharmguru’s exam insights:
Metabolism is the sum of all chemical reactions in the body. In exams, pay special attention to: (1) Glycolysis and its energetics, (2) The TCA cycle and its significance, (3) The regulation of blood glucose by insulin and glucagon, (4) β-oxidation of fatty acids, (5) The urea cycle, and (6) Electron Transport Chain. Remember: “Metabolism is the engine of life—understanding it is understanding how the body works.”
REFERENCES AND FURTHER READING
- Lehninger, A. L., Nelson, D. L., & Cox, M. M. (2017). Lehninger Principles of Biochemistry (7th ed.). W. H. Freeman.
- Berg, J. M., Tymoczko, J. L., & Stryer, L. (2019). Biochemistry (9th ed.). W. H. Freeman.
- Satyanarayana, U., & Chakrapani, U. (2021). Biochemistry (5th ed.). Elsevier.
- Vasudevan, D. M., Sreekumari, S., & Vaidyanathan, K. (2022). Textbook of Biochemistry for Medical Students (9th ed.). Jaypee Brothers.
- National Institutes of Health (NIH). (2022). Metabolism Resources. Retrieved from https://www.nih.gov.
Disclaimer: This article is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare professionals for medical concerns.
written by:
Dr. N. Sujith Kumar
