Ch. 15 - Metabolism: Basic Concepts and Themes

Metabolism is Composed of Many Interconnect Relationships

  • energy is required for mechanical work, muscle contraction, and cell movement, active transport, and biosynthesis

    • phototrophs: capture energy from sunlight (photosynthesis)

    • chemotrophs: capture energy through the oxidation of chemicals


  • metabolism (intermediary metabolism): network of chemical reactions that carry out energy extraction and synthesis of new material

    • metabolic pathway: series of linked reactions by which fuels are degrade and large molecules are constructed

      • ex: glycolysis = 10 step pathway converting glucose into pyruvate


  • themes common to ALL metabolic reactions:

    • ATP is used as an energy currency to link energy-releasing (exergonic) to energy-requiring (endergonic) pathways

    • either sunlight or the oxidation of chemical fuels powers ATP formation

    • ~100 molecules serve as activated intermediates

  • metabolism only uses a few kinds of enzymatic mechanisms

  • they are highly regulated because pathways are independent

  • many of the enzymes involved in metabolism are organized into large complexes

    • increases speed and efficiency

    • allows efficient/safe processing of unstable or toxic intermediates


  • metabolism is either destructive (yields energy) or constructive (requires energy)

    • catabolism: reactions that break down complex molecules into simpler ones to capture energy in useful forms

      • general equation: fuel (carbs, fats) → CO2 + H2O + useful energy

    • anabolism: reactions that construct a more complex molecule from simpler molecules by using energy

      • general equation: CO2 + H2O + useful energy → complex molecules

  • a thermodynamically unfavorable reaction can be driven by coupling to a favorable reaction

    • over free-energy change for a chemically coupled series of reactions = the sum of free-energy changes of the individual steps

      • allows for the coupling of thermodynamically unfavorable and favorable reactions in enzyme active site

ATP is Universal Currency of Free Energy in Biological Systems

  • free energy derived from oxidation of food and from light is transformed in ATP

    • ATP is energy rich because its triphosphate unit contains 2 phosphoanhydride linkages


  • release of free energy is by the:

    • formation of new covalent bonds

    • formation of noncovalent interactions with water

    • increase in entropy

  • ∆G for ATP hydrolysis is under typical cellular condition (-30 kJ mol-1)

    • some reactions are catalyzed by GTP, UTP, or CTP (energetically equivalent)

  • acyl group carrier coenzyme A, NAD+ and FAD (electron carriers) are derivatives of ATP


  • ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions

    • unfavorable conversion of the compound A into compound B can be made possible by coupling to ATP hydrolysis

    • equilibrium constant K’eq at 25℃ reavelas the conversion of A to B cannot take place when the molar ration of B to A is equal to or greater than 1.1 × 10-3

    • coupling the conversion of A to B with ATP hydrolysis renders the formation of B exergonic (energy-releasing)

    • coupling the reactions under standard conditions changes the equilibrium ratio of B to A


  • compounds with phosphoryl-transfer potential higher than ATP can be used to make ATP from ADP

    • ex: phosphoenolpyruvate, 1,3-bisphosphoglycerate, and creatine phosphate

      • creatine phosphate serves as a reservoir of high potential phosphoryl groups

        • creatine kinase catalyzes the regeneration of ATP from creatine phosphate and ADP

        • ∆G of hydrolysis of creatine phosphate = -43.1 kJ mol-1 (energetically favorable)

Oxidation of Carbon Fuels is an Important Source of Cellular Energy

  • ATP is the principal immediate donor of free energy, but it is limitied

    • must be constantly regenerated from ADP


  • oxidation of fuel molecules takes places 1 carbon at a time

    • yields CO2

      • the more reduced a carbon atom is, the more free energy is released

        • ex: methane (more hydrogens attached) produces more energy than carbon dioxide (less hydrogens attached)

        • fats are more efficient as a fuel source than carbohydrates because the carbon in fats are more reduced

    • electrons are ultimately accepted by oxygen to form H2O


  • compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis

    • glyceraldehyde 3-phosphate: metabolite of glucose formed during glucose oxidation

      • C-1 carbon is an aldehyde and is not in its most oxidized state

      • oxidation dos not occur directly

        • carbon oxidation generates 1,3-biphosphoglycerate and the electrons released are captured by NAD+ to form NADH

          • 1,3-BPG has high phosphoryl-transfer potential → its hydrolysis can be coupled to ATP synthesis


  • ion gradients across membranes provide an important form of cellular energy that can be coupled to ATP synthesis

    • oxidation of fuel molecules or phototrophy produce electrochemical potentials of ion gradients across membranes

      • serves as a versatile means of coupling thermodynamically unfavorable and favorable reactions

    • in animals, 90% of ATP is generated when the energy of a proton gradient is coupled with ATP synthesis (oxidative phosphorylation)


  • energy from food is extracted in 3 stages:

    1. large molecules in food are broken down into smaller unites

    2. small molecules are degraded into simple units (ex: Acetyl CoA → plays a role in metabolism)

    3. ATP is produced from the complete oxidation of the acetyl unit of acteyl CoA into CO2

Many Metabolic Pathways Contain Recurring Themes

  • energetically activated carriers: small molecules to which a chemical group or electrons have been added, then can be donated to another molecule

    • frequently act as coenzymes or cosubstrates

      • ex: ATP = activated carrier of phosphoryl groups

    • EXAMPLE: NADH = activated carrier of electrons for fuel oxidation

      • nicotinamide adenine dinucleotide (NAD+) accepts a proton and 2 electrons from an oxidized substrate to form reduced NADH. Ring accepts the H-

    • EXAMPLE: FADH2 = activated carrier of electrons for fuel oxidation

      • Flavin adenine dinucleotide (FAD) accepts 2 protons and 2 electrons in the oxidation of a substrate to form (FADH2 = reduced form)

      • electrons and protons are carried by the reactive isoalloxazine ring component

        • derivative of vitamin riboflavin

    • EXAMPLE: NADPH = activated carrier of reductive biosynthesis

      • in most biosynthesis, precursors are more oxidized than products → ATP and reducing power are needed

      • NADPH is the electron donor in most reductive biosynthesis

    • EXAMPLE: Coenzyme A: activated carrier of 2 carbon fragments

      • carrier of acyl groups that is derived from vitamin B3 (pantothenate)

        • terminal sulfhydryl group = reactive part

        • acyl groups link to CoA by thioester bonds to form acyl CoA

          • acetyl CoA = acteyl linked to CoA


  • kinetic stability allows enzymatic control over the flow of energy

    • NADH, NADPH, and FADH2 react slowly with O2 in the absences of a catalyst

    • ATP and acetyl CoA are hydrolyzed slowly in the absence of a catalyst

  • a small set of carriers accomplishes the majority of the exchanges of activated groups in metabolic pathways


  • key reactions are reiterated throughout metabolism

    • oxidation-reduction: electron transfer

      • useful energy is often derived from the oxidation of carbon compounds

    • group transfer

      • used to synthesize ATP in signaling pathways

      • ex: phosphoryl group transfer

    • hydrolytic

      • cleaves bonds by the addition of water, usually to degrade large molecules

      • ex: hydrolytic cleave of peptide bonds in proteins

    • carbon bond cleavage (other than hydrolysis or oxidation)

      • ex: conversion of 6-carbon molecule fructose 1,6-bisphosphate into two 3-carbon fragments during glycolysis

      • ex: dehydration → generation of phosphoenolpyruvate from 2-phosphoglycerate

    • isomerization

      • rearranges atoms within a molecule, typically to prepare for a subsequent reaction

      • ex: conversion of citrate to isocitrate

    • ligation requiring ATP cleavage

      • forming covalent bonds using free energy from ATP hydrolysis

      • ex: formation of oxaloacetate from pyruvate and CO2


  • metabolic processes are regulated in 3 ways:

    1. altering amount of enzymes

      • amount of enzyme depends on rate of synthesis and rate of degradation

      • level of enzymes adjusted by changing the rate of transcription of the genes encoding them   

        • ex: HMG-CoA reductase enzyme controls cholesterol biosynthesis

    2. restricting accessibility to substrates

      1. enzymes downstream of an allosterically controlled enzyme

      2. compartmentalization often segregates opposed reactions

        • ex: fatty acid oxidation occurs in mitochondrial matrix, while fatty acid synthesis occurs in cytoplasm

    3. regulating catalytic activity of enzymes allosterically or by P.T. covalent modification

      • feedback inhibition = high conc. of end product inhibit the enzyme that performs the committed step in the pathway

        • ex: ATCase is feedback inhibited by CTP and feedback activated by ATP

      • reversible covalent modification can control catalytic rates of enzymes

        • ex: phosphorylation