Unit 5: Metabolic Fate of Biomolecules: Carbohydrates, Lipids, Proteins & Amino Acids

Course Information

• Course Name & Code: Pharmaceutical Biochemistry-I (PHL-309)
• Topic: Metabolic Fate of Biomolecules: Carbohydrates, Lipids, Proteins & Amino Acids
• Credit Hours: 3

Learning Objectives

By the end of this topic, students will be able to:

• Describe the digestion, absorption, and metabolic pathways of carbohydrates, lipids, and proteins.
• Explain glycolysis, the citric acid cycle, and oxidative phosphorylation in energy production.
• Discuss the beta-oxidation of fatty acids and the biosynthesis of lipids and cholesterol.
• Describe the metabolism of amino acids, including urea cycle and heme synthesis.
• Correlate metabolic disorders with their clinical and pharmaceutical significance.

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Core Content

PART A: CARBOHYDRATE METABOLISM

5.1 Digestion and Absorption of Carbohydrates

Dietary Sources: Starch, glycogen, sucrose, lactose, and cellulose (indigestible fiber).

Digestion Process:

Absorption:

• Glucose and Galactose: Absorbed via SGLT-1 (sodium-dependent glucose transporter) in the intestinal epithelium.
• Fructose: Absorbed via GLUT-5 (facilitated diffusion).
• All monosaccharides are transported into the bloodstream via GLUT-2 at the basolateral membrane and delivered to the liver via the portal vein.

Pharmaceutical Relevance:

• Lactose Intolerance: Deficiency of lactase → osmotic diarrhea, abdominal cramps.
• Sucrase-Isomaltase Deficiency: Causes sucrose intolerance.
• Drug-Drug Interactions: Some drugs (e.g., acarbose) inhibit α-glucosidase to slow carbohydrate absorption in diabetes mellitus.

5.2 Glycolysis (Embden-Meyerhof Pathway)

Definition: The anaerobic breakdown of glucose (6-carbon) into two molecules of pyruvate (3-carbon) with the net production of ATP and NADH.

Site: Cytoplasm of all cells.

Phases of Glycolysis:

Phase 1: Energy Investment Phase (Steps 1-5)

• Glucose is phosphorylated to glucose-6-phosphate (ATP consumed).
• Rearranged to fructose-6-phosphate.
• Phosphorylated to fructose-1,6-bisphosphate (second ATP consumed).
• Cleaved into glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
• DHAP is converted to G3P.

Phase 2: Energy Generation Phase (Steps 6-10)

• G3P oxidized to 1,3-bisphosphoglycerate (NADH produced).
• Phosphoryl transfer to ADP → ATP produced (substrate-level phosphorylation).
• 3-phosphoglycerate → 2-phosphoglycerate → Phosphoenolpyruvate (PEP).
• PEP transfers phosphate to ADP → ATP produced (second substrate-level phosphorylation).
• Pyruvate is formed.

Net Equation:

Glucose + 2 NAD⁺ + 2 ADP + 2 Pi → 2 Pyruvate + 2 NADH + 2 H⁺ + 2 ATP + 2 H₂O

Energetics:

• Total ATP consumed: 2
• Total ATP produced: 4 (substrate-level phosphorylation)
• Net ATP gain: 2 ATP (anaerobic); NADH yields additional ATP aerobically via ETC.

Regulation of Glycolysis:

• Key Regulatory Enzymes: Hexokinase/Glucokinase, Phosphofructokinase-1 (PFK-1), Pyruvate Kinase.
• PFK-1 is the most important regulatory enzyme:
  • Activators: AMP, Fructose-2,6-bisphosphate.
  • Inhibitors: ATP, Citrate, H⁺ (low pH).

Clinical/Pharmaceutical Relevance:

• Diabetes Mellitus: Impaired glycolysis due to insulin deficiency.
• Lactic Acidosis: Excessive anaerobic glycolysis → lactate accumulation.
• Cancer: Warburg effect (increased glycolysis even in presence of oxygen).
• Enzyme Deficiencies: Pyruvate kinase deficiency causes hemolytic anemia.

5.3 Aerobic Breakdown of Glucose

After glycolysis, pyruvate enters the mitochondria for complete oxidation.

A. Pyruvate Dehydrogenase Complex (PDH Complex)

• Converts pyruvate to acetyl-CoA in the mitochondrial matrix.
• Reaction: Pyruvate + CoA + NAD⁺ → Acetyl-CoA + CO₂ + NADH + H⁺
• Requires: Thiamine (TPP), Lipoic acid, FAD, CoA, NAD⁺.
• Regulation:
  • Activators: Insulin, high Ca²⁺ (in muscle).
  • Inhibitors: Acetyl-CoA, NADH, ATP (feedback inhibition).

B. Tricarboxylic Acid (TCA) Cycle / Citric Acid Cycle / Krebs Cycle

Definition: A series of enzyme-catalyzed reactions in the mitochondrial matrix that completely oxidizes acetyl-CoA to CO₂ and H₂O, generating NADH, FADH₂, and GTP.

Steps of TCA Cycle:

Energetics per Acetyl-CoA:

• 3 NADH → 7.5 ATP (ETC)
• 1 FADH₂ → 1.5 ATP (ETC)
• 1 GTP → 1 ATP
• Total = 10 ATP per Acetyl-CoA

Regulation of TCA Cycle:

• Key enzymes: Citrate Synthase, Isocitrate Dehydrogenase, α-Ketoglutarate Dehydrogenase.
• Activators: Ca²⁺, ADP.
• Inhibitors: ATP, NADH, Succinyl-CoA.

Anaplerotic Reactions: Replenish TCA cycle intermediates (e.g., pyruvate carboxylase converts pyruvate to oxaloacetate).

Pharmaceutical Relevance:

• Fluoroacetate Poisoning: Blocks TCA cycle (inhibits aconitase).
• Arsenic Poisoning: Inhibits α-ketoglutarate dehydrogenase and pyruvate dehydrogenase.
• Vitamin Deficiencies: Beriberi (thiamine deficiency) impairs PDH and TCA.

5.4 Pentose Phosphate Pathway (PPP) / Hexose Monophosphate Shunt

Definition: Alternative pathway for glucose oxidation producing NADPH and pentoses (ribose-5-phosphate) for nucleotide synthesis.

Site: Cytoplasm (liver, adipose tissue, erythrocytes, adrenal cortex, lactating mammary glands).

Phases:

1. Oxidative Phase (Irreversible):
   • Glucose-6-P → 6-Phosphogluconolactone (G6PD; NADPH produced).
   • 6-Phosphogluconolactone → 6-Phosphogluconate.
   • 6-Phosphogluconate → Ribulose-5-P + CO₂ (6PGD; NADPH produced).
2. Non-Oxidative Phase (Reversible):
   • Ribulose-5-P ↔ Ribose-5-P (for nucleotide synthesis).
   • Interconversion of sugars to generate glycolytic intermediates (Fructose-6-P and Glyceraldehyde-3-P).

Products:

• NADPH: Reductive biosynthesis (fatty acids, steroids) and antioxidant defense (maintains reduced glutathione).
• Ribose-5-Phosphate: Precursor for nucleotide and nucleic acid synthesis.

Regulation:

• G6PD is the rate-limiting enzyme.
• Activated by: Insulin, NADP⁺.
• Inhibited by: NADPH (feedback inhibition).

Clinical/Pharmaceutical Relevance:

• G6PD Deficiency (Favism): Hemolytic anemia upon oxidative stress (e.g., sulfa drugs, primaquine, fava beans).
• Importance in erythrocytes: only source of NADPH to maintain reduced glutathione.
• Liver: provides NADPH for lipogenesis and cholesterol synthesis.

5.5 Glycogen Metabolism

A. Glycogenesis (Glycogen Synthesis)

• Definition: Synthesis of glycogen from glucose for storage.
• Site: Liver and skeletal muscle.
• Process:
  1. Glucose → Glucose-6-P (Hexokinase/Glucokinase)
  2. Glucose-6-P → Glucose-1-P (Phosphoglucomutase)
  3. Glucose-1-P + UTP → UDP-Glucose + PPi (UDP-Glucose Pyrophosphorylase)
  4. UDP-Glucose + Glycogen (n) → Glycogen (n+1) + UDP (Glycogen Synthase – rate-limiting enzyme)
  5. Branching enzyme (α-1,6-glucosidase) creates branch points.

B. Glycogenolysis (Glycogen Breakdown)

• Definition: Breakdown of glycogen to release glucose.
• Site: Liver (releases glucose to blood); muscle (releases glucose-6-P for local energy).
• Process:
  1. Glycogen (n) + Pi → Glycogen (n-1) + Glucose-1-P (Glycogen Phosphorylase)
  2. Glucose-1-P → Glucose-6-P (Phosphoglucomutase)
  3. In liver: Glucose-6-P → Glucose + Pi (Glucose-6-Phosphatase – absent in muscle).
  4. In muscle: Glucose-6-P enters glycolysis.

Regulation:

• Glycogen Synthase: Activated by insulin; inhibited by epinephrine/glucagon.
• Glycogen Phosphorylase: Activated by epinephrine/glucagon (via cAMP); inhibited by insulin.

Clinical/Pharmaceutical Relevance:

• Glycogen Storage Diseases (GSD):
  • Von Gierke's Disease (GSD I): Glucose-6-phosphatase deficiency → severe hypoglycemia, hepatomegaly.
  • McArdle's Disease (GSD V): Muscle glycogen phosphorylase deficiency → muscle cramps on exertion.
• Drugs: Glucagon used to treat severe hypoglycemia.

5.6 Gluconeogenesis

Definition: Synthesis of glucose from non-carbohydrate precursors (lactate, amino acids, glycerol, propionate).

Site: Liver (major) and kidneys (minor).

Precursors:

• Lactate (from muscle via Cori cycle).
• Glucogenic amino acids (alanine via glucose-alanine cycle).
• Glycerol (from lipid breakdown).
• Propionate (from odd-chain fatty acids).

Key Reactions (Bypasses of Irreversible Glycolytic Steps):

Energetics: Cost: 6 ATP equivalents per glucose molecule synthesized.

Regulation:

• Stimulated by: Cortisol, Glucagon, Epinephrine (fasting state).
• Inhibited by: Insulin (fed state).

Clinical/Pharmaceutical Relevance:

• Diabetes Mellitus: Excessive gluconeogenesis contributes to hyperglycemia.
• Metformin: Decreases gluconeogenesis by activating AMPK.
• Cori Cycle: Lactate from muscle is recycled to glucose in the liver.
• Glucose-Alanine Cycle: Amino groups transported to liver for urea synthesis.

5.7 Energetics of Carbohydrate Metabolism

Complete Oxidation of Glucose:

Glucose + 6 O₂ + 36/38 ADP + 36/38 Pi → 6 CO₂ + 6 H₂O + 36/38 ATP (Old yield = 36/38; modern estimate = 30-32 due to NADH shuttle cost)

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PART B: LIPID METABOLISM

5.8 Digestion and Absorption of Lipids

Dietary Sources: Triglycerides (90%), phospholipids, cholesterol esters, fat-soluble vitamins.

Digestion Process:

Absorption:

• Micelles deliver lipids to brush border of enterocytes.
• Lipids diffuse or are transported via transporters into enterocytes.
• Inside enterocytes, lipids are re-esterified to triglycerides, phospholipids, and cholesterol esters.
• Lipids packaged into chylomicrons and secreted into lymph → thoracic duct → bloodstream.

Pharmaceutical Relevance:

• Orlistat: Inhibits pancreatic lipase; used for weight loss.
• Cholestyramine: Bile acid sequestrant; lowers cholesterol.
• Fat Malabsorption: Cystic fibrosis, celiac disease, pancreatic insufficiency.

5.9 Beta-Oxidation of Fatty Acids (β-Oxidation)

Definition: Breakdown of fatty acids into acetyl-CoA units for energy production, occurring in the mitochondrial matrix.

Activation:

• Fatty acids activated to fatty acyl-CoA in cytoplasm using 2 ATP equivalents (ATP → AMP + PPi).
• Carnitine shuttle transports long-chain fatty acyl-CoA into mitochondria.

Steps of β-Oxidation per Cycle:

Each cycle shortens the fatty acid chain by 2 carbons and produces 1 FADH₂, 1 NADH, and 1 Acetyl-CoA.

Energetics for Palmitic Acid (C16:0):

• Number of cycles = 7
• Products: 8 Acetyl-CoA, 7 FADH₂, 7 NADH
• ATP yield: 8 Acetyl-CoA × 10 = 80 ATP
• 7 FADH₂ × 1.5 = 10.5 ATP
• 7 NADH × 2.5 = 17.5 ATP
• Total = 108 ATP
• Activation cost = 2 ATP
• Net = 106 ATP per palmitate molecule

Regulation:

• Rate-limiting enzyme: Carnitine palmitoyltransferase I (CPT-I) in outer mitochondrial membrane.
• Inhibited by: Malonyl-CoA (a key intermediate of fatty acid synthesis).
• Stimulated by: Fasting, exercise, glucagon, epinephrine.

Clinical/Pharmaceutical Relevance:

• Carnitine Deficiency: Impaired β-oxidation → hypoglycemia, cardiomyopathy.
• Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD): Accumulation of medium-chain fatty acids; hypoketotic hypoglycemia.
• Hypoglycin (Jamaican Vomiting Sickness): Toxin inhibits β-oxidation.

5.10 Biosynthesis of Fatty Acids (Lipogenesis)

Definition: Synthesis of fatty acids from acetyl-CoA, occurring primarily in cytosol of liver, adipose tissue, and lactating mammary glands.

Site: Cytoplasm.

Process Overview:

1. Transport of Acetyl-CoA from Mitochondria to Cytosol:
   • Acetyl-CoA + Oxaloacetate → Citrate (mitochondria)
   • Citrate → Acetyl-CoA + Oxaloacetate (cytosol; via ATP-citrate lyase)
2. Activation of Acetyl-CoA to Malonyl-CoA:
   • Acetyl-CoA + CO₂ + ATP → Malonyl-CoA (Acetyl-CoA Carboxylase – rate-limiting enzyme; requires biotin).
   • Activators: Insulin, Citrate.
   • Inhibitors: Palmitoyl-CoA, Glucagon, Epinephrine.
3. Fatty Acid Synthase (FAS) Complex:
   • Multi-enzyme complex catalyzing sequential addition of 2-carbon units from malonyl-CoA.
   • Each cycle: Acetyl (2C) + Malonyl (2C) → 4C chain + CO₂.
   • Product: Palmitate (C16:0) after 7 cycles.

Energy Cost for Palmitate (C16:0) Synthesis:

7 Acetyl-CoA + 14 NADPH + 14 H⁺ + 7 ATP → Palmitate + 7 CoA + 14 NADP⁺ + 7 ADP + 7 Pi

Regulation:

• Fed State: Insulin stimulates fatty acid synthesis.
• Fasting State: Glucagon/epinephrine inhibit via phosphorylation of acetyl-CoA carboxylase.

Pharmaceutical Relevance:

• Statins: Inhibit HMG-CoA reductase; reduce cholesterol.
• Fatty acid synthesis inhibitors: potential targets for obesity and cancer therapy.
• Metabolic Syndrome: Dysregulated lipogenesis contributes to fatty liver.

5.11 Biosynthesis of Neutral Lipids

A. Triacylglycerol (Triglyceride) Synthesis

• Definition: Esterification of glycerol-3-phosphate with fatty acyl-CoA to form triglycerides.
• Process:
  1. Glycerol-3-P + 2 Fatty acyl-CoA → Phosphatidic acid (2 acyl groups).
  2. Phosphatidic acid → Diacylglycerol (DAG) (dephosphorylation).
  3. DAG + Fatty acyl-CoA → Triacylglycerol (TAG).
• Source of Glycerol-3-P:
  • Liver/kidneys: from glycerol (glycerol kinase).
  • Adipose tissue: from dihydroxyacetone phosphate (glycolysis).

B. Phospholipid Synthesis

• Phosphatidic acid → Cytidine diphosphate-diacylglycerol (CDP-DAG).
• Reaction with serine, inositol, or choline yields phosphatidylserine, phosphatidylinositol, and lecithin.

Pharmaceutical Relevance:

• Lecithin: used as emulsifier.
• Phospholipids: essential for liposomal drug delivery.

5.12 Biosynthesis of Cholesterol

Definition: Cholesterol is synthesized from acetyl-CoA via the mevalonate pathway.

Site: Cytoplasm of hepatocytes (mainly); also intestine and adrenal cortex.

Process Overview:

1. Acetyl-CoA → HMG-CoA (β-Hydroxy-β-methylglutaryl-CoA): 3 Acetyl-CoA → HMG-CoA (HMG-CoA Synthase).
2. HMG-CoA → Mevalonate: HMG-CoA + 2 NADPH → Mevalonate (HMG-CoA Reductase – rate-limiting enzyme).
3. Mevalonate → Isopentenyl pyrophosphate (IPP) (via phosphorylation and decarboxylation).
4. Condensation of IPP units → Squalene (30-carbon isoprenoid).
5. Squalene → Lanosterol (cyclization).
6. Lanosterol → Cholesterol (multiple steps).

Regulation:

• HMG-CoA Reductase is the key regulatory enzyme:
  • Inhibited by: Cholesterol (feedback), Statins (competitive), Glucagon.
  • Stimulated by: Insulin, Thyroid hormone.

Pharmaceutical Relevance:

• Statins (Atorvastatin, Rosuvastatin): HMG-CoA reductase inhibitors; lower serum cholesterol.
• Bile Acid Sequestrants: Bind bile acids, increasing cholesterol excretion.
• Ezetimibe: Inhibits intestinal cholesterol absorption.
• Fibrates: Decrease triglyceride synthesis.

Cholesterol Functions:

• Structural component of cell membranes.
• Precursor for steroid hormones (cortisol, aldosterone, sex hormones).
• Precursor for bile acids and Vitamin D.
• Myelin sheath formation.

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PART C: PROTEIN AND AMINO ACID METABOLISM

5.13 Digestion and Absorption of Proteins

Dietary Sources: Meat, fish, eggs, dairy, legumes.

Digestion Process:

Absorption:

• Free amino acids: absorbed via Na⁺-dependent transporters and H⁺-dependent carriers.
• Small peptides (di/tripeptides): absorbed via PEPT-1 transporters; hydrolyzed to amino acids inside enterocytes.
• Transported to liver via portal circulation.

Pharmaceutical Relevance:

• Protein Malabsorption: Celiac disease, pancreatic insufficiency.
• PEPT-1 Transporters: target for drug delivery (e.g., some antibiotics like cephalexin).

5.14 Metabolism of Essential and Non-Essential Amino Acids

A. General Amino Acid Metabolism

1. Transamination:
   • Transfer of α-amino group from amino acid to α-keto acid.
   • Enzyme: Aminotransferases (Transaminases) – require pyridoxal phosphate (PLP, Vitamin B6).
   • Examples:
     • Alanine + α-KG ↔ Pyruvate + Glutamate (ALT)
     • Aspartate + α-KG ↔ Oxaloacetate + Glutamate (AST)
2. Oxidative Deamination:
   • Removal of amino group as ammonia (NH₃).
   • Glutamate Dehydrogenase: Glutamate + H₂O + NAD(P)⁺ → α-KG + NH₃ + NAD(P)H + H⁺.
   • Ammonia converted to urea in liver (urea cycle).

B. Urea Cycle (Ornithine Cycle)

Definition: Series of reactions in liver converting ammonia (NH₃) into urea for excretion.

Site: Liver (mitochondria and cytosol).

Steps:

Regulation:

• CPS-I activated by N-acetylglutamate.

Clinical/Pharmaceutical Relevance:

• Urea Cycle Disorders: Hyperammonemia (e.g., Ornithine Transcarbamoylase deficiency).
• Hepatic Encephalopathy: Liver dysfunction → ↑ ammonia → neurotoxicity.
• Drugs: Sodium phenylbutyrate, Sodium benzoate – lower ammonia levels.

C. Metabolism of Specific Amino Acids

D. Essential vs. Non-Essential Amino Acids

• Essential: Valine, Leucine, Isoleucine, Methionine, Phenylalanine, Threonine, Tryptophan, Lysine, Histidine (in children).
• Non-Essential: Alanine, Aspartate, Glutamate, Serine, etc. – synthesized from carbohydrate metabolism intermediates via transamination.

5.15 Biosynthesis and Catabolism of Haemins and Porphyrins

Definition: Porphyrins are cyclic compounds of four pyrrole rings linked by methene bridges. Heme is protoporphyrin IX + Fe²⁺.

A. Biosynthesis of Heme

• Site: Liver (cytochrome P450), Bone marrow (hemoglobin).
• Steps:

Diagram: Heme Synthesis Simplified

Glycine + Succinyl-CoA | ALA (δ-Aminolevulinic acid) | Porphobilinogen (PBG) | Hydroxymethylbilane | Uroporphyrinogen III | Coproporphyrinogen III | Protoporphyrinogen IX | Protoporphyrin IX | HEME (Protoporphyrin IX + Fe²⁺)

Regulation:

• ALA Synthase is rate-limiting.
  • Inhibited by: Heme (feedback).
  • Induced by: drugs that induce CYP450 (increase heme demand).

B. Catabolism of Heme

Site: Reticuloendothelial cells (spleen, liver, bone marrow), macrophages.

Process:

1. Heme Oxygenase: Heme → Biliverdin + CO + Fe²⁺.
   • Biliverdin (green) → bilirubin.
   • CO: signaling molecule (vasodilation).
   • Fe²⁺: recycled.
2. Biliverdin Reductase: Biliverdin → Bilirubin (unconjugated/indirect).
3. Transport: Bilirubin bound to albumin → liver.
4. Liver Conjugation: Bilirubin + UDP-Glucuronic acid → Bilirubin diglucuronide (conjugated/direct) – glucuronyl transferase.
5. Excretion: Conjugated bilirubin → bile → intestine → urobilinogen → stercobilin (feces), urobilin (urine).

Clinical/Pharmaceutical Relevance:

Pharmaceutical Importance:

• Porphyrin-based drugs: Photodynamic therapy (PDT) for cancer.
• Bilirubin as diagnostic marker (liver function tests).
• Hematin: used in acute porphyria to suppress heme synthesis.
• Chloramphenicol: causes dose-dependent anemia; may interfere with heme synthesis.

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4. Diagrams/Tables

Diagram 1: Overview of Carbohydrate Metabolism

Table: Summary of Fatty Acid Oxidation vs. Synthesis

Diagram: Heme Synthesis Simplified

Glycine + Succinyl-CoA | ALA (δ-Aminolevulinic acid) | Porphobilinogen (PBG) | Hydroxymethylbilane | Uroporphyrinogen III | Coproporphyrinogen III | Protoporphyrinogen IX | Protoporphyrin IX | HEME (Protoporphyrin IX + Fe²⁺)

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5. Exam Angle

Short Questions (2-5 marks)

1. Differentiate between glycolysis and gluconeogenesis.
2. Write the net equation of glycolysis.
3. Name the irreversible enzymes of glycolysis and their bypasses in gluconeogenesis.
4. What is the function of the pentose phosphate pathway?
5. Define essential fatty acids and give examples.
6. Write the sequence of reactions in β-oxidation of fatty acids.
7. What is the urea cycle? Name the site and key enzymes.
8. Define transamination and oxidative deamination.
9. Name the porphyrias and their enzyme defects.
10. Why is glucose-6-phosphatase important?
11. Differentiate between direct (conjugated) and indirect (unconjugated) bilirubin.
12. Explain the Cori cycle.

Long Essays (10+ marks)

1. Describe the citric acid cycle in detail with its energetics and regulation. Add a note on its pharmaceutical importance.
2. Discuss the digestion and absorption of carbohydrates. Explain glycolysis and its regulation.
3. Write a detailed note on β-oxidation of fatty acids, including its energetics and clinical significance.
4. Describe the urea cycle and the metabolism of amino acids. Add a note on disorders of the urea cycle.
5. Give a detailed account of heme synthesis and its regulation. Discuss the types of jaundice.
6. Compare and contrast the metabolism of carbohydrates, lipids, and proteins during fed and fasting states.

Key Points Frequently Tested

• Glycolysis: Irreversible steps (hexokinase, PFK-1, pyruvate kinase); ATP yield; regulation.
• TCA Cycle: Key enzymes; inhibitors; anaplerotic reactions; ATP yield.
• Hormonal Regulation: Insulin vs. Glucagon/Epinephrine on metabolic pathways.
• Clinical Correlations: G6PD deficiency, PKU, MCADD, porphyrias, jaundice, hyperammonemia.
• ATP Yields: Complete oxidation of glucose (~30-32 ATP) and palmitic acid (106 ATP).
• Drug Targets: Statins (HMG-CoA reductase), Orlistat (lipase), Metformin (gluconeogenesis).

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6. Summary Box

• Carbohydrate metabolism involves glycolysis (aerobic/anaerobic), TCA cycle, PPP, glycogenolysis, and gluconeogenesis. These pathways are tightly regulated by insulin and glucagon.
• Lipid metabolism includes β-oxidation for energy, fatty acid synthesis (lipogenesis), and cholesterol biosynthesis. β-oxidation of palmitate yields 106 ATP.
• Protein metabolism involves digestion to amino acids, transamination/deamination, and the urea cycle for ammonia detoxification. Essential amino acids must come from the diet.
• Heme synthesis occurs in the liver and bone marrow from glycine and succinyl-CoA. Heme catabolism produces bilirubin, which is conjugated in the liver and excreted via bile.
• Clinical correlations include metabolic disorders (G6PD deficiency, PKU, porphyrias, jaundice), drug targets (statins, orlistat), and diagnostic markers (bilirubin, liver enzymes).

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7. References

• Chatterjee, M. N., & Shinde, R. (2011). Textbook of Medical Biochemistry (8th ed.). Jaypee Brothers Medical Publishers.
• Murray, R. K., Bender, D. A., Botham, K. M., Kennelly, P. J., Rodwell, V. W., & Weil, P. A. (2015). Harper's Illustrated Biochemistry (30th ed.). Lange Medical Books / McGraw-Hill Education.
• Nelson, D. L., & Cox, M. M. (2012). Lehninger Principles of Biochemistry (6th ed.). W. H. Freeman.
• Champe, P. C., & Harvey, R. A. (2013). Lippincott's Illustrated Reviews: Biochemistry (6th ed.). Lippincott Williams & Wilkins.
• Peet, A., Lieberman, M. A., & Marks, A. (2012). Marks' Basic Medical Biochemistry (4th ed.). Lippincott Williams & Wilkins.