BIOL 102 W3: Metabolism

First law of thermodynamics

Energy cannot be created or destroyed, only transformed

Second law of thermodynamics

Every energy transfer increases the entropy of the universe

Entropy

Measure of disorder

Reducing agent

Electron donor

Oxidizing agent

Electron acceptor

Spontaneous reaction

An energetically favourable reaction that occurs without a continuous energy supply

Metabolic pathway

A step-by-step process that alters a specific molecule into a certain product

Catabolic pathways

Release energy and break down complex molecules into their simpler parts

Anabolic pathways

Consume energy to build complex molecules from simpler compounds

Biosynthetic pathways

Another term for anabolic pathways

Kinetic energy

Energy associated with the relative motion of objects

Thermal energy

A type of kinetic energy associated with the random movement of atoms and molecules

Heat

Thermal energy transferred from one object to another

Potential energy

Energy matter possesses because of its location or structure

Chemical energy

A type of potential energy available for release in a chemical reaction

System

The matter under study in thermodynamics

Surroundings

Everything outside of a thermodynamic system

Isolate system

Cannot exchange energy or matter with its surroundings

Open system

Can transfer energy and matter to its surroundings

Free energy

Portion of a systems energy that is able to do work when temperature and pressure are constant within the system

Negative free energy

Indicates a spontaneous reaction

What makes spontaneous reaction more stable in its final state

It has less free energy than its initial state, therefore the system is less likely to change

Chemical equilibrium

The point where the forward and backward reactions occur at the same rate

Equilibrium

A state of maximum stability

Why can’t systems at equilibrium do work

They cannot spontaneously change

Exergonic reactions

Energy releasing

Endergonic reactions

Energy absorbing

Standard conditions

1M each of reactant and product, 25*C, pH 7

Meaning of energy stored in bonds

Potential energy can be released when new bonds form after original bonds break, as long as products are of lower free energy than reactants

Defining feature of life

Metabolism as a whole is never at equilibrium

Types of cellular work

Chemical, transport, mechanical

Chemical cellular work

Pushing of endergonic reactions that wouldn’t spontaneously occur

Cellular transport work

Pumping of substances across the membrane against the direction of spontaneous movement

Mechanical work

E.g beating of cilia, contraction of muscles, movement of chromosomes

Energy coupling

The use of an exergonic process to drive an endergonic one

ATP structure

Consists of ribose, adenine, and a chain of three phosphates

Inorganic phosphate

HOPO₃^2-

ATP hydrolysis

The terminal phosphate bond is broken by addition of a water molecule and a molecule of inorganic phosphate leaves

Why does ATP hydrolysis release so much energy

All phosphate groups are negatively charged and repel making the group unstable like a compressed spring

Phosphorylated intermediate

A short-lived unstable reactant with phosphate covalently that drives energy coupling

Process of mechanical work involving motor proteins “walking”

ATP binds to motor protein, is hydrolyzed to release ADP and P_i, and another ATP bonds changing the protein’s shape resulting in movement along cytoskeleton

Catalyst

Chemical agent that speeds up a reaction without being consumed in it

Activation energy

Initial energy required to contort reactants so their bonds can break and begin the reaction

Transition state

Unstable condition when the reactants have absorbed enough energy for the bonds to break

Limitations of enzymes

Cannot make an endergonic reaction exergonic, they can only speed up reactions that would happen regardless

Substrate

Reactant an enzyme acts on

Enzyme-substrate complex

An enzyme bound to its substrate

Active site

Pocket or groove of an enzyme where catalysis occurs

Mechanisms enzymes use to lower activation energy

Orienting substrates so a reaction can occur, bending critical bonds into transition state, providing an environment more conducive to reaction, amino acid interactions

Factors influencing enzyme activity

Temperature, pH, specific chemicals

Cofactors

Non-protein helpers for catalytic activity

Coenzyme

An organic cofactor

Competitve inhibitors

Resemble the substrate and bind to the active site to inhibit enzyme activity

Noncompetitve inhibition

Binds to the enzyme away from active site and changes the shape in a way that prevents binding

How enzymes evolve

Mutations change amino acids in proteins which could result in an enzyme with novel functions which could be beneficial to the organism and passed on

Allosteric regulation

When a protein’s function at one site is affected by a regulator bound to a different site, resulting in inhibition or stimulation of an enzyme’s activity

Structure of allosterically regulated enzymes

Most consist of 2+ subunits and oscillate between a catalytically active shape and an inactive one

Allosteric inhibitor

Stabilizes the enzyme’s inactive form

Allosteric activator

Stabilizes the enzyme’s active form

ATP as an allosteric regulator

ATP acts as an enzyme inhibitor whereas ADP acts as an activator

Function of allosteric enzymes

Control the rates of important reactions in catabolic and anabolic pathways

Cooperativity

A kind of allosteric activation where a substrate binding to one subunit of a multisubunit enzyme causes all subunits to change their shape, increasing activity at all sites

Feedback inhibition

When the end product of a pathway binds to and inhibits an enzyme that acts earlier in the pathway in order to stop the pathway

Bioenergetics

Study of the flow of energy through living organisms

Steps of energy investment phase of glycolysis

Glucose phosphorylation, rearrangement, second phosphorylation, cleavage

Glucose phosphorylation

An ATP is consumed to phosphorylate glucose forming G6P

Rearrangement (glycolysis)

Glucose-6-phosphate is rearranged into fructose-6-phosphate

Second phosphorylation (glycolysis)

Another ATP is consumed to phosphorylate F6P and form fructose-1,6-bisphosphate

Cleavage (glycolysis)

Unstable fructose-1,6-bisphosphate splits into 2 G3P molecules

Steps of energy payoff phase of glycolysis

Oxidation and phosphorylation, first ATP generation, phosphate relocation, dehydration, second ATP generation

Oxidation and phosphorylation (glycolysis)

G3P dehydrogenase oxidizes G3P, reducing NAD+ to NADH and releasing an H+, Pi bonds to G3P to become 1,3-BGP

First ATP generation (glycolysis)

Phosphoglycerate kinase strips a phosphate from unstable 1,3-BGP and transfers it to ADP, making 3-PG and ATP (substrate-level phosphorylation)

Phosphate relocation (glycolysis)

Phosphoglycerate mutase moves phosphate from 3rd to 2nd carbon to make it less stable, resulting in 2-PG

Dehydration (glycolysis)

Enolase removes a water from 2-PG resulting in highly energetic, unstable PEP

Second ATP generation (glycolysis)

Pyruvate kinase transfers phosphate from PEP to ADP to make pyruvate and ATP (substrate-level phosphorylation)

Glycolysis location

Cytosol

Pyruvate oxidation location

Mitochondrial matrix

Steps of pyruvate oxidation

Decarboxylation, oxidation, acetyl group transfer

Decarboxylation (pyruvate oxidation)

An enzyme strips a carbon off the 3C pyruvate which exits as CO2 and leaves a 2C acetyl fragment

Oxidation (pyruvate oxidation)

The remaining 2C acetyl fragment is oxidized and NAD+ is reduced to NADH (plus H+)

Acetyl group transfer (pyruvate oxidation)

A high-energy sulfur bond attaches CoA to the acetyl fragment forming Acetyl-CoA

Reactants of pyruvate oxidation

2 pyruvate, 2 NAD+, 2 CoA

Products of pyruvate oxidation

2 CO2, 2 NADH, 2 Acetyl-CoA

Location of citric acid cycle

Mitochondrial matrix

Reactants of citric acid cycle

1 Acetyl-CoA, 3 NAD+, 1 FAD, 1 ADP, 1 Pi, 2 H2O

Products of citric acid cycle

1 CoA (reused), 1 CO2 (waste), 3 NADH, 1 FADH2, 1 ATP, 3 H+

Steps of citric acid cycle

Citrate synthesis, isomerization of citrate, oxidative decarboxylation of isocitrate, second oxidative decarboxylation, substrate-level phosphorylation, dehydrogenation of succinate, hydration of fumarate, dehydrogenation of malate

Citrate synthesis (TCA)

2C acetyl group detaches from Acetyl-CoA and binds to 4C oxaloacetate to make 6C citrate

Isomerization of Citrate (TCA)

An enzyme rearranges citrate to isocitrate to make it less stable

Oxidative Decarboxylation of Isocitrate

Isocitrate is oxidized and a carbon leaves as CO2. NAD+ is reduced and a 5C molecule is leftover

Second Oxidative Decarboxylation

Another carbon leaves as CO2, another NAD+ is reduced and the leftover molecule binds to CoA forming 4C succinyl-CoA

Substrate-Level Phosphorylation (TCA)

Bond between CoA and 4C molecule breaks, the energy is used to quickly attach Pi to GDP making GTP, which becomes ATP, and succinate

Dehydrogenation of Succinate

Succinate is oxidized by an enzyme embedded in IMM to become fumarate and FAD accepts 2 electrons and protons to become FADH2

Hydration of Fumarate

A water is added to rearrange fumarate into malate

Dehydrogenation of Malate

Malate is oxidized, NAD+ is reduced, and the molecule reverts to oxaloacetate

Steps of cellular respiration

Glycolysis, pyruvate oxidation, citric acid cycle, oxidative phosphorylation

Steps of ETC (oxidative phosphorylation)

Oxidation of coenzymes, sequential redox reactions, active proton dislocation, reduction of terminal electron acceptor

Steps of chemiosmosis (oxidative phosphorylation)

Establishment of proton motive force, passive proton diffusion and rotational catalysis

Oxidation of coenzymes (oxidative phosphorylation)

NADH is oxidized at Complex I and FADH2 is oxidized at Complex II releasing high-energy electrons into ETC

Sequential redox reactions (OP)

Electrons are transferred through protein complexes and mobile carriers (ubiquinone, Cyt c)