Metabolism basic concepts and design I. Overview II. Forms of cellular energy III. Oxidation of carbon fuels IV. Features of metabolic pathways
I.
Overview of Metabolism –
1. Metabolism: The highly integrated network of chemical reaction in the cell (body). It is divided into two functional blocks:
1) Catabolsim: degradation; how do cell extract energy (ATP) and reducing power (NADPH) from their environments.
P 2) Anabolism: biosynthesis; how do cell synthesize macromolecules for their growth and maintenance.
Anabolism ----------- catabolism
ADP + Pi
ATP
NADP+
NADPH
II. Cellular forms of chemical energy Catabolism produces what compounds for energy utilization??
1. ATP (Adenosine TriPhosphate) 2. Other compounds with high phosphoryl transfer potential 3. Reducing power (NADPH, NADH, FADH2)
1. ATP is the Cellular Energy Currency A. Energy released from foods is captured in the molecular form of ATP. B. ATP contains two high energy bonds, and hydrolysis of ATP yields energy. ATP + H2O ------> ADP + Pi + 7 kcal/mol energy
Structure of ATP
ATP + H2O ------> ADP + Pi + 7 kcal/mol energy
• Hydrolysis of high energy bonds of ATP in two ways:
ATP is a high-energy-containing compound
What does the high-energy compound mean?
ďƒ˜A high-energy compound has a greater free energy of hydrolysis than a typical compound. ďƒ˜It contains one or more very reactive bonds (strained bonds) that require less energy than that generally required to break a chemical bond. ďƒ˜Consequently, the hydrolysis of high-energy compounds produce greater-than-normal energy (high energy)
Why is ATP a high-energy compound? (1) Electrostatic repulsion among negatively charged oxygens of phosphoanhydrides of ATP
(2) Products are more stable than reactants ADP, Pi or AMP, PPi are more stable than on ATP General factors contribute to the high phosphoryl-group transfer of ATP? Resonance stabilization, electrostatic repulsion, & stabilization due to hydration (how easy for water to bind) Two strongly electronwithdrawing groups compete for the lone pairs of electrons
How much ATP is used daily by a typical human? A human uses ~40 kg of ATP per day. There is only about 100 g ATP available. How is it regenerated?
ATP is used and regenerated rapidly. ATP is regenerated from ADP and Pi, using the energy from catabolic processes.
1. ATP (Adenosine TriPhosphate)
2. Other compounds with high phosphoryl transfer potential 3. Reducing power (NADPH, NADH, FADH2)
• Phosphoryl-group-transfer potential - the ability of a compound to transfer its phosphoryl group • Energy-rich or high-energy compounds have group transfer potentials equal to or greater than that of ATP
• Low-energy compounds have group transfer potentials less than that of ATP
Relative phosphoryl-group-transfer potentials • Metabolites with high phosphorylgroup-transfer potentials are intermediates in catabolic pathways
• They can donate a phosphoryl group to ADP to form ATP
Phosphagens: Energy-rich storage molecules in animal muscle • Phosphocreatine and phosphoarginine are phosphoamides
• Have higher group-transfer potentials than ATP • Produced in muscle during times of ample ATP • Used to replenish ATP when needed via creatine kinase reaction
Second energy currency 1. ATP (Adenosine TriPhosphate) 2. Other compounds with high phosphoryl transfer potential
3. Reducing power (NADPH, NADH, FADH2) Reduced Coenzymes Conserve Energy from Biological Oxidations
• carbohydrates, lipids, & proteins are oxidized in the catabolic pathways • Oxidizing agent - accepts electrons, is reduced • Reducing agent - loses electrons, is oxidized • Oxidation of one molecule must be coupled with the reduction of another molecule Ared + Box
Aox + Bred
NAD+ = nicotinamide adenine dinucleotide
NADH used for ATP synthesis
nicotinamide
NADP+ = nicotinamide adenine dinucleotide phosphate
NADPH used for reductive biosynthesis
adenine ribose NADH: R= H NADPH: R= Pi
nicotinamide
adenine
nicotinamide
FAD = flavin adenine dinucleotide
Why are two different electron carriers, NAD+ and FAD, involved in metabolism?
The flavin-containing coenzyme is involved in one-electron transfers as well as two-electron transfers, whereas NAD+ is involved only in twoelectron transfers. In addition, FAD has a higher standard reduction potential than NAD+ (Table 13-3), that is, a lower ď „Gď‚°', and can therefore be reduced by reactants with insufficient free energy to reduce NAD+.
How is Reduction Potential is related to Free-Energy? • The reduction potential of a reducing agent is a measure of its thermodynamic reactivity • Relationship between standard free-energy change and the standard reduction potential:
Go’ = -nFEo’
n = # electrons transferred F = Faraday constant (96.48 kJ V-1)
Eo’ = Eo’electron acceptor - Eo’electron donor
Electron Transfer from NADH & FADH2 Provides Free Energy that produces ATP from ADP, Pi • Most NADH formed in metabolic reactions in aerobic cells is oxidized by the respiratory electron-transport chain • Energy used to produce ATP from ADP, Pi • Half-reaction for overall oxidation of NADH:
NAD+ + 2H+ + 2e-
NADH + H+ (Eo’ = -0.32V)
Where does body’s energy come from? I. II.
Overview Forms of cellular energy
III. Oxidation of carbon fuels IV. Features of metabolic pathways
Oxidation of carbon releases energy
During oxidation, electrons are used to reduce coenzymes such as NAD+ to form NADH.
I. Overview II. Forms of cellular energy III. Oxidation of carbon fuels
IV. Features of metabolic pathways 1. Forms of metabolic pathways 2. Metabolism Proceeds by Discrete Steps
3. Metabolic Pathways Are Regulated
4. Metabolic processes are compartmentalized
Features of metabolic pathways 1. Forms of metabolic pathways
Linear
Cyclic
Spiral
2. Metabolism Proceeds by Discrete Steps • Multiple-step pathways permit control of energy input and output • Catabolic multi-step pathways provide energy in smaller stepwise amounts) that can be used by the cell
• Each enzyme in a multistep pathway usually catalyzes only one single step in the pathway
• Control points occur in multistep pathways
3. Metabolic Pathways Are Regulated • Metabolism is highly regulated to permit organisms to respond to changing conditions • 3 principal ways of regulation: (1) The amount of enzymes Enzyme synthesis & degradation - transcription - gene expression
(2) The enzyme catalytic activities Allosteric regulation Reversable covalent modification –(de)phosphorylation
(3) The accessibility & supply of substrates
• Feedback inhibition: Product of a pathway controls the rate of its own synthesis by inhibiting an early step (usually the first “committed” step (unique to the pathway)
• Feed-forward activation: Metabolite early in the pathway activates an enzyme further down the pathway
4. Metabolic processes are compartmentalized
• Compartmentation of metabolic processes permits:
- separate pools of metabolites within a cell - simultaneous operation of opposing metabolic paths - high local concentrations of metabolites
- coordinated regulation of enzymes • Example: fatty acid synthesis enzymes (cytosol), fatty acid breakdown enzymes (mitochondria)
Metabolism is divided into what two processes? How are the two processes unified?
Catabolism degrades molecules to produce ATP and reducing power Anabolism uses ATP and reducing power to synthesize molecules for cell maintenance, growth and reproduction
Why is ATP an energy rich molecule? ATP contains two phosphoanhydride bonds that are unstable due to resonance instability and electrostatic repulsion.
What is the advantage of “pyrophosphate cleavage� of ATP? Sometimes the cleavage of the terminal phosphoanhydride bond of ATP is not sufficient to drive some very endergonic metabolic processes. The overall process involves the cleavage of both phosphoanhydride bonds of ATP in order to supply sufficient free energy to drive the endergonic process.
Why are the vitamins niacin and riboflavin necessary for metabolism? These vitamins are not synthesized in humans, but they are components of coenzymes required for redox reactions in metabolism. Niacin is a component of NAD+, and riboflavin is a component of FAD.
Where do carbon fuels come from in the body? Polymers
monomers
Acetyl-CoA
CO2 + ATP
Catabolism can be divided into 3 stages