Comprehensive Bullet-Point Notes: Carbohydrate Metabolism, Aerobic/Anaerobic Strategies & Sterol Biology Across Taxa

Distribution of Carbohydrates in Vertebrates & Invertebrates

  • Sugars occur free or as parts of complex molecules; major classes and examples:
    • Pentoses: D-ribose, 2-deoxy-D-ribose (DNA sugar)
    • Hexoses: D-glucose (ubiquitous blood sugar), D-galactose, D-mannose, D-fructose, L-fucose
    • Uronic acids: D-glucuronic, L-iduronic acids (detoxification, GAG structure)
    • Hexosamines: D-glucosamine, D-galactosamine (chitin, cartilage)
    • Pentose-phosphate–pathway intermediates appear as phosphates: D-erythrose-4-P, D-ribulose-5-P, D-xylulose-5-P, D-sedoheptulose-7-P
  • Invertebrate-specific sugars:
    • L-arabinose & D-xylose (pentoses) and L-rhamnose (deoxyhexose) in many polysaccharides
    • D-xylose links glycosaminoglycan (GAG) chain to core protein in mucopolysaccharides
    • D-arabinose in unusual sponge nucleosides
    • L-galactose restricted to snail galactans; D-galacturonic acid seldom in animals (brain, elasmobranch & gastropod secretions)
  • Ascarylose (3,6-dideoxy-L-mannose) unique to bacteria & nematode Ascaris; forms glycolipid “ascaryl alcohol” within egg-shell ascarosides → confers extreme chemical resistance
  • Inositols (polyalcohols):
    • Myo-inositol universal in membranes; free in mammalian seminal fluid; phosphate esters modulate Hb O₂-affinity in bird/reptile RBCs
    • Scyllo-inositol widespread; L-chiro-inositol only in cockroach fat-body & haemolymph
  • Sialic acids (N-acetyl/ N-glycolyl-neuraminic acids; >30 variants):
    • Substitutions possible at C-4,7,8,9 (acetyl, glycolyl, lactyl, methyl, sulphate, phosphate)
    • Occur mainly bound in gangliosides & glycoproteins; present in mammalian milk/urine, many bacteria, protozoa (e.g., Trypanosoma cruzi) but absent from fungi, algae, higher plants, sponges, arthropods, molluscs, Plasmodium

Extracellular Carbohydrates & Environmental Adaptation

  • Insects: extracellular glycerol, sorbitol, trehalose, erythritol, threitol, mannitol; glucose, fructose; amino acids (proline, alanine) & antifreeze proteins accumulate for cold tolerance
  • Trehalose = major haemolymph sugar (<glucose except in honey-bee where glucose≈fructose≈trehalose)
  • Nematodes: extracellular sugars enable extreme desiccation tolerance
  • Vertebrate blood glucose concentrations (mmol L⁻¹): mammals 3–11, birds 7–12, reptiles 2–9, teleosts 1–5, amphibians 0.5–1.6; invertebrate haemolymph <2
  • Mammalian seminal plasma: fructose primary sperm nutrient ± sorbitol, myo-inositol; glucose mostly absent (exception: human, rat, mouse, guinea-pig)

Overview of Glycolysis (Embden-Meyerhof-Parnas)

  • Universal cytosolic pathway; only a few anaerobic bacteria/archaea lacking phosphofructokinase-1 cannot complete pathway
  • Two phases:
    1. Preparatory (investment): glucose → fructose-1,6-bisP; consumes 2 ATP
    2. Pay-off: cleavage → two triose-P → pyruvate; produces 4 ATP + 2 NADH → net \Delta ATP = +2
  • Key enzymes (Mg²⁺ or K⁺ cofactors): Hexokinase, PFK-1, Aldolase, Triose-P isomerase, G3P dehydrogenase, PGK, PGM, Enolase, Pyruvate kinase

Glycolysis in Kinetoplastids (e.g., Trypanosoma, Leishmania)

  • Possess defective mitochondria; early steps housed in microbody-like organelles = glycosomes
  • Glycosomal contents: first 7 glycolytic enzymes + glycerol-3-P kinase & glycerol kinase
  • Only G3P-DH & PGK have cytosolic isoforms
  • Compartment confers separate redox & ATP balance:
    • Under anaerobiosis: glycerol-3-P → glycerol + ATP (reverse GK)
    • Net products per glucose: 1 glycerol + 1 pyruvate (↓ATP yield)
  • Regulatory divergence: Hexokinase & PFK unresponsive to typical modulators → potential drug targets

Carbohydrate-Metabolizing Insects (RQ = 1.0)

  • Orders: Diptera (flies), Hymenoptera (bees, wasps), Dictyoptera (cockroaches)
  • Traits:
    • Short flight bursts, rely on trehalose → glucose (via trehalase) then glycolysis
    • High glycolytic/gluconeogenic enzyme activity; low lipid-metabolic activity; phosphocreatine system absent
  • Muscle types:
    • Non-fibrillar (locust, roach): neural frequency = contraction frequency
    • Fibrillar (flies, bees): myogenic oscillation >> nerve signal rate; nerve impulse initiates cycle
  • Additional substrates:
    • Sorbitol → fructose-6-P
    • UDP-galactose → UDP-glucose → G-1-P → G-6-P
    • Mannose → mannose-6-P → fructose-6-P
  • Long flight: glycogen mobilisation → G-1-P → G-6-P
  • Anaerobic glycolysis absent (no lactate DH activity)

Bees

  • Nectar (sucrose) split by α-glucosidase; contaminant starch by amylase; glucose → gluconic acid + H₂O₂ via glucose oxidase (antiseptic honey)

Insects Using Both Carbohydrates & Lipids (RQ drop 1.0\to0.7)

  • Orthoptera, Lepidoptera, Coleoptera, Hemiptera
  • Trehalose/glycogen fuel take-off; prolonged flight switches to fatty acids
  • Adipokinetic hormone triggers fat-body DAG release; DAG + HDLp + apoLp-III → LDLp → muscle → DAG hydrolysis → FFA + glycerol (glycerol used in trehalose synthesis)
  • FFA transported as carnitine esters into mitochondria → β-oxidation
  • Analogous to vertebrate VLDL system

Amino-Acid Fuelling (Proline)

  • Bees, wasps, tsetse flies: proline oxidation in mitochondria replenishes TCA intermediates (pyruvate-fumarate shuttle) enabling high carbohydrate flux during flight onset

Carbohydrate Metabolism in Fish

  • Muscle: \sim92\% white (anaerobic); glycogen phosphorylase A activated during burst → high glycolytic flux
  • 80–90\% blood lactate oxidised to CO2 + H2O (cori cycle minor); oxidation mainly in heart & red muscle; limited gluconeogenesis
  • Fibre types: I (red, aerobic), IIa (intermediate), IIb (white, anaerobic)

Carbohydrate Metabolism in Plants

Calvin Cycle (C₃ pathway)

  1. Fixation: CO_2 + \text{RuBP} \xrightarrow{\text{Rubisco}} 2\,3\text{-PGA}
  2. Reduction: 3\text{-PGA} \to Glyceraldehyde\,3\text{-P} using ATP & NADPH
  3. Regeneration: triose-P → RuBP
  • Overall: 3\,CO2 + 9\,ATP + 6\,NADPH → Glyceraldehyde\,3\text{-P} + 9\,ADP + 8\,Pi + 6\,NADP^+

C₄ Pathway

  • Spatial separation: Mesophyll (PEP carboxylase → oxaloacetate/malate) vs bundle-sheath (Calvin)
  • Costs extra 2\,ATP/CO_2 but suppresses photorespiration; favoured in hot, high-light habitats (e.g., maize, sugarcane)

CAM Pathway

  • Temporal separation: stomata open at night (PEPC → malate stored in vacuole); daylight: malate decarboxylation provides CO_2 for Calvin with closed stomata → extreme water use efficiency (cacti, pineapples)

Aerobic & Anaerobic Metabolism in Animals

Aerobic Respiration

  1. Glycolysis (cytosol): Glucose \to 2\,Pyruvate + 2\,ATP + 2\,NADH
  2. TCA cycle (matrix): 2\,Acetyl\,CoA \to 2\,ATP + 6\,NADH + 2\,FADH_2
  3. ETC (inner membrane): \approx26–28\,ATP + H_2O

Aerobic Glycolysis (Warburg Effect)

  • Rapidly proliferating cells (tumours, activated lymphocytes) ferment glucose → lactate even with O₂
  • Advantages:
    1. Lactic acid export acidifies micro-environment → invasion, immune evasion
    2. Glucose-6-P feeds pentose-P pathway (NADPH, ribose)
    3. Less O₂ dependency during hypoxia
  • Biochemical shifts: mitochondrial-bound hexokinase isoform (no feedback by G-6-P); slow pyruvate kinase M (PK-M) diverts intermediates to biosynthesis
  • HIF-1 activated by hypoxia or intense anaerobic training → up-regulates glycolytic enzymes, GLUT1/3 & VEGF → angiogenesis

Exercise Metabolism

  • Aerobic (distance): gradual switch glycogen → FFA; RQ falls 1.0\to0.7; AMP-activated kinase + ↓malonyl-CoA activate CPT-I (fat oxidation)
  • Anaerobic (sprint): rely on muscle glycogen & phosphocreatine; lactate accumulates; training increases mitochondrial biogenesis → delays lactate reliance

Vertebrate Anaerobic Glycolysis

  • Glucose/Glycogen + 2\,ADP + 2\,P_i \to 2\,Lactate + 2\,ATP
  • Requires high lactate dehydrogenase to re-oxidise NADH
  • Lactic acid removal (when O₂ returns):
    1. Lactate \to Pyruvate \to CO2 + H2O (oxidation)
    2. Lactate \to Glucose/Glycogen (gluconeogenesis; prominent in fish, amphibians, reptiles)

Phosphagens

  • Creatine-P (vertebrates) / Arginine-P (most invertebrates): \text{Phosphagen} + ADP \leftrightarrow \text{Phosphagen}_{deP} + ATP via creatine/arginine kinase; serves as immediate ATP buffer during burst activity

Exercise Interplay Examples

  • Fish: steady cruise (red muscle, aerobic) vs escape burst (white muscle, anaerobic)
  • Crustacean tail-flip: initial ATP from arginine-P, prolonged from anaerobic glycolysis
  • Insect flight muscle: entirely aerobic; up to \sim50\% volume mitochondria, supplied by tracheal O₂
  • Molluscs (squid, scallop): pyruvate → octopine via octopine dehydrogenase
  • Amphibians: frogs (anaerobic jump burst, high LDH) vs toads (aerobic sustained)

Environmental (Habitat-Dependent) Anaerobiosis

  • Oxygen regulation (constant \dot{V}{O2}) until critical P{O2} → oxygen conformity
  • Aquatic invertebrates (bivalves, annelids) & some fish tolerate prolonged anoxia by metabolic depression (down to \le10\% basal rate)
  • Goldfish & crucian carp convert lactate → ethanol + CO_2 in muscle via modified alcohol DH; ethanol diffuses across gills → avoids acidosis & allows months-long survival under ice
  • End-product patterns:
    • Activity-dependent: lactate or opines (octopine, etc.)
    • Habitat-dependent: succinate, acetate, propionate, alanine (yield up to 7\,ATP/glucose)
  • Excretion of end products or conversion to neutral compounds (ethanol) mitigates acidosis

Sterols & Steroids Across Taxa

General Features

  • Sterols rigidify & condense eukaryotic membranes; parent molecule: cholesterol (animals), β-sitosterol/stigmasterol (plants), ergosterol (fungi)
  • Many taxa produce steroidal glycosides, saponins, alkaloids for defense

Vertebrate Sterols

  • Marine fish: up to \tfrac13 sterols as bioactive glycosides
  • Human cholesterol balance: ≈50% diet / 50% de novo (liver)
  • LCAT esterifies cholesterol in HDL → reverse cholesterol transport to liver via SR-BI; deficiencies (autosomal recessive) cause low HDL, corneal opacities (“fish-eye disease”), normocytic anemia, premature atherosclerosis
  • Cholesterol → steroid hormones (C₂₁ corticosteroids/progestins; C₁₉ androgens; C₁₈ estrogens) & bile acids (≈1 g day⁻¹ synthesis)

Insect Sterols

  • Cannot synthesise sterols de novo; obtain from diet or symbionts
  • Many herbivores 24-dealkylate C₂₈/C₂₉ phytosterols → cholesterol; some insects (beetle, housefly, cockroach) lack this ability
  • Silkworm demands cholestane side-chain sterols; sterols serve as membrane components & ecdysteroid precursors

Marine Invertebrates

  • Tunicates, annelids, crustaceans, molluscs: cholesterol dominant; bivalves also Δ⁵,⁷-sterols & 4α-methyl sterols; cephalopods produce testosterone
  • Echinoderms: Δ⁵ or Δ⁷ C₂₇ sterols; unique C₂₆ sterols, large stores of sterol sulphates, and potent asterosaponins (membrane-toxic)
  • Cnidarians: complex Δ⁵ sterols; unique gorgosterol (cyclopropane side-chain) in soft corals w/ symbiotic dinoflagellates

Protozoa

  • Tetrahymena synthesises tetrahymanol (hopanoid-like) anaerobically; sterol presence suppresses synthesis
  • Amoebae (Acanthamoeba, Naegleria) synthesize cholesterol via cycloartenol pathway

Plant Sterols (Phytosterols)

  • Major: campesterol, β-sitosterol, stigmasterol, 24-methylcholesterol
  • Regulate membrane fluidity; stigmasterol weaker in ordering effect
  • Sterols + glycosphingolipids form lipid rafts influencing protein localisation
  • Stress responses: stigmasterol accumulates under heat/salinity/drought
  • Campesterol precursor to brassinosteroids (≈70 analogues) – growth hormones; potential anti-cancer agents
  • Plants also produce progesterone, testosterone, phytoecdysteroids (defence vs insects)
  • Sterol esters store surplus sterol & intermediates in lipid droplets
  • Human nutrition: plant sterols/stanols compete with cholesterol absorption, ↓LDL-c; β-sitosterol induces tumour-cell apoptosis via PI3K/Akt inhibition & ROS generation

Fungal Sterols & Antifungals

  • Dominant sterol: ergosterol (Ascomycota, Basidiomycota); Oomycetes synthesize fucosterol; lower fungi produce cholesterol & derivatives; some parasites lack sterol synthesis (utilise host cholesterol)
  • Roles: membrane stability, stress response, dimorphism, pathogenicity
  • Antifungal drug classes & targets:
    1. Azoles (fluconazole, etc.): inhibit lanosterol 14α-demethylase → ↓ergosterol, ↑14-methyl sterols; resistance via efflux pumps, enzyme mutation
    2. Allylamines (terbinafine): block squalene epoxidase
    3. Morpholines (amorolfine): inhibit C-14 sterol reductase & C-8 isomerase → ignosterol accumulation
    4. Polyenes (amphotericin B): bind ergosterol → pores; resistance by altered sterol content
  • Balance of biosynthesis/degradation regulated transcriptionally & by feedback to avoid free sterol toxicity

Ecdysteroids (Arthropod Moulting Hormones)

  • Cholesterol-derived; retain extended side-chain, highly hydroxylated (↑water-solubility)
  • 20-Hydroxyecdysone main active form converted by 20-monooxygenase; other routes: 3-dehydroecdysone reductase, 25-hydroxylation of ponasterone A
  • Non-arthropod invertebrates & plants produce ecdysteroid analogues (phytoecdysteroids) – plant defence by disrupting insect development; high concentrations allow eco-friendly pest control

Bacterial Hopanoids

  • Hopanoids (e.g., diplopterol) are triterpenoids from squalene; insert into bacterial membranes enhancing rigidity analogous to sterols
  • Some pathogens (Mycoplasma) scavenge host sterols for growth