M

Metabolism & Nutrient Fate

Metabolism: Core Themes

  • Definition & Scope
    • Collective term for all chemical reactions sustaining life
    • Mathematically expressed as: \text{Metabolism}=\text{Catabolism}+\text{Anabolism}
    • Constant balance between energy release (to power work/heat) and energy investment (to build/repair)
  • Big-picture Significance
    • Links nutrition, endocrinology, physiology & cellular biology
    • Malfunction → diabetes, obesity, cachexia, inborn errors of metabolism
    • Practical/ethical lens: informs public-health policy, food security, sustainable agriculture

Fate of Digested Nutrients

  • Immediate Energy
    • Oxidised in catabolic pathways → ATP + heat
    • Drives muscular contraction, ion pumps, active transport, biosynthesis
  • Raw Material for Biosynthesis
    • Precursors for new macromolecules (proteins, nucleic acids, polysaccharides, lipids)
    • Vital for growth, repair & immune competence
  • Storage Pathways
    • Glycogenesis → glycogen (liver, skeletal muscle)
    • Lipogenesis → triglycerides (adipocytes, liver)
    • Protein accretion in lean tissues

Reaction Types

  • Catabolic Reactions
    • Break chemical bonds; large → small molecules
    • Net \Delta G<0, releasing energy (often captured as ATP, NADH, FADH$_2$)
    • Examples: glycolysis, β-oxidation, proteolysis
  • Anabolic Reactions
    • Form chemical bonds; small → large molecules
    • Require energy input (usually from ATP/NADPH)
    • Examples: glycogen synthesis, fatty-acid synthase, ribosomal protein synthesis

Cellular Energy Currency

  • Goal: Convert nutrient energy into a format used by nearly every enzyme system
  • Energy Source: Macromolecule oxidation (mainly glucose & triglycerides)
  • Currency: ATP, augmented by GTP, UTP, CTP for specialized reactions

ATP: Structure & Function

  • Diagrammatic Features
    • Adenine (nitrogenous base) + ribose ⇒ adenosine
    • Three phosphate groups linked by two high-energy phosphoanhydride bonds
    • Hydrolysis: \text{ATP}+\text{H}2\text{O} \rightarrow \text{ADP}+\text{P}i+\text{Energy} (≈ 7.3 \text{ kcal·mol}^{-1} under standard conditions)
  • Role Shuttling Energy
    • Catabolism → synthesises ATP
    • Anabolism/transport → splits ATP, harnessing energy
  • Recycling Rate: Entire body pool (~50–75 g) turned over every minute at rest

Review of Major Biological Macromolecules

  • Carbohydrates
    • Monomer: glucose
    • Polymers: amylose & amylopectin (starch), glycogen, cellulose (fiber)
    • Key bond: glycosidic linkage (\alpha or \beta)
  • Nucleic Acids
    • Pentose (ribose or deoxyribose) + phosphate + nitrogenous base (purine/pyrimidine)
    • Phosphodiester bonds; bases A, G (purines) & C, T, U (pyrimidines)
  • Proteins
    • Built from 20 amino acids via peptide bonds
    • Levels: primary → secondary (\alpha-helix/\beta-sheet) → tertiary → quaternary (e.g. hemoglobin)
  • Lipids
    • Triglyceride = glycerol + 3 fatty acids
    • Also phospholipids, cholesterol, steroid hormones, myelin

Preferred ATP Energy Sources

  • Priority Hierarchy
    • 1st: glucose & triglycerides
    • Brain & erythrocytes: require glucose (brain can use ketone bodies after prolonged fasting)
    • Other tissues switch flexibly between lipids & glucose
    • Last-resort: amino acids (protein catabolism)
  • Physiological Set-point: Blood glucose maintained ≈ 70\text{–}100\,\text{mg·dL}^{-1}

Inter-Conversion Pathways

  • Producing Glucose (Gluconeogenesis)
    • Substrates: lactate, pyruvate, certain glucogenic amino acids
    • Location: liver (90 %), kidney cortex (10 %)
  • From Glucose
    • Glycogenesis (short-term storage)
    • Lipogenesis (excess → triglycerides)

Hormonal Control of Energy Metabolism

  • Insulin
    • Released when blood glucose↑
    • Actions: ↑ cellular glucose uptake; ↑ glycogen & lipid synthesis; ↓ glucagon secretion
  • Glucagon
    • Trigger: blood glucose↓, amino acids↑
    • Actions: ↑ hepatic gluconeogenesis & glycogenolysis; ↑ lipolysis; ↓ insulin
  • Cortisol
    • Released under stress/circadian drive
    • Mobilises fuel: ↑ gluconeogenesis, protein catabolism; anti-insulin effects
  • Growth Hormone + IGF-1
    • Stimuli: sleep, exercise, high-protein meal, hypoglycaemia, trauma
    • Effects: ↑ protein synthesis (esp. muscle), bone growth, lipolysis

Measuring Energy Intake/Expenditure

  • Calorie Conventions
    • 1\,\text{cal} (chemistry) = heat to raise 1\,\text{g H}_2\text{O} by 1^{\circ}\text{C}
    • 1\,\text{Calorie}=1\,\text{kcal}=1000\,\text{cal}
  • Macronutrient Energy Density
    • Carbohydrate: \approx4\,\text{kcal·g}^{-1}
    • Protein: \approx4\,\text{kcal·g}^{-1}
    • Lipid: \approx9\,\text{kcal·g}^{-1}
  • Practical Note: Food labels use “Calories” (kcal); accurate tracking informs weight management & metabolic research

Carbohydrate Metabolism Beyond Energy

  • Dietary Fiber
    • Non-digestible polysaccharides
    • Water-soluble (e.g. pectins) → modulate cholesterol/glucose absorption
    • Insoluble (e.g. cellulose) → bowel motility, microbiome substrate
  • Other Roles
    • Ribose ↑ nucleotide synthesis (e.g. ATP, DNA/RNA)
    • Glycoproteins & glycolipids in cell-cell recognition (immune & developmental biology)

Lipids: Non-Fuel Functions

  • Membrane Architecture: phospholipid bilayer integrity & fluidity
  • Cholesterol Derivatives: steroid hormones, bile salts, vitamin D
  • Cell Signalling: eicosanoids, phosphatidylinositol cascade
  • Myelin: electrical insulation of neurons

Amino Acids & Protein Metabolism

  • Functional Diversity
    • Structure (collagen, cytoskeleton, muscle), enzymes, antibodies, hormones, transport proteins (albumin, hemoglobin)
  • Nitrogen Disposal
    • Catabolism liberates NH$_3$ (toxic)
    • Urea Cycle (liver): converts NH$3$ + CO$2$ → urea → excreted in urine
    • Failure → hyperammonaemia (neurological damage)

Micronutrients

  • Vitamins
    • Water-soluble: B-complex (B$1$–B${12}$), C
    • Fat-soluble: A, D, E, K
  • Minerals
    • Major (>100 mg·day$^{-1}$): Na, K, Ca, P, Mg, Cl
    • Trace: Fe, Cu, Zn, I, S, Mn, Co, F, Se, Cr, Mo
  • Metabolic Co-factors: many serve as enzyme prosthetic groups (e.g. Fe in cytochromes, Zn in DNA-binding proteins)

Essential Nutrients

  • Cannot be Synthesised in Adequate Quantities
    • Fatty Acids: linoleic (ω-6), α-linolenic (ω-3); possibly arachidonic (conditional)
    • Amino Acids: 9 indispensable (His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val) + 6 conditionally essential in infants/illness
    • Vitamins: most, except some vitamin D (skin) & K (gut flora)
    • Minerals: all must be ingested
  • Dietary Planning Implication: variety of whole foods ensures sufficiency; vegan/vegetarian diets require B$_{12}$ monitoring

Integrative & Ethical/Philosophical Connections

  • Systems Perspective: Hormonal orchestration exemplifies homeostasis — dynamic stability despite fluctuating intake/needs
  • Public Health: Understanding metabolism guides interventions against metabolic syndrome & malnutrition
  • Environmental Ethics: Choosing nutrient-dense, sustainably produced foods reduces ecological footprint
  • Equity: Access to essential nutrients is a global justice issue, influencing cognitive development & disease burden

Key Numerical & Formula Recap

  • \text{ATP hydrolysis energy}\approx7.3\,\text{kcal·mol}^{-1}
  • 1\,\text{Calorie}=1\,\text{kcal}=1000\,\text{cal}=4184\,\text{J}
  • Macronutrient energy densities: \text{CHO}=4\,\text{kcal·g}^{-1},\;\text{Protein}=4\,\text{kcal·g}^{-1},\;\text{Fat}=9\,\text{kcal·g}^{-1}
  • Blood glucose homeostasis: 70\text{–}100\,\text{mg·dL}^{-1}\;(3.9\text{–}5.6\,\text{mmol·L}^{-1})

Study Tips & Further Connections

  • Cross-link these notes with prior lectures on cellular respiration (glycolysis → TCA → ETC) for mechanistic depth
  • Practice drawing metabolic maps to visualise substrate flows & hormonal “switches”
  • Apply quantitative skills: calculate caloric requirements, respiratory quotient (\text{RQ}), & Gibbs free-energy changes
  • Ethical reflection: evaluate diet fads against biochemical principles above — critical thinking > marketing claims.