Biochemistry - Chapter 15: Metabolism: Basic Concepts and Themes

These flashcards cover essential vocabulary and concepts related to metabolism from the lecture notes.

Metabolism

A highly integrated network of chemical reactions that carry out energy extraction and synthesis of new material.

• composed of many interconnected reactions

Catabolism

A set of metabolic pathways that break down complex molecules into simpler ones to capture energy.

Anabolism

A set of metabolic pathways that construct larger molecules from smaller units, consuming energy.

ATP

A nucleotide consisting of adenine, a ribose, and a triphosphate unit, which acts as the primary energy carrier in cells.

• is the universal currency of free energy in biological systems

• Free energy derived from oxidation of food and from light is transformed into __

• Active in complex with Mg2+ or Mn2+

Phototrophs

Organisms that capture energy from sunlight, such as all photosynthetic organisms.

Chemotrophs

Organisms that capture energy through the oxidation of chemicals, such as all animals.

Glycolysis

A 10-step metabolic pathway converting glucose to pyruvate.

Phosphoryl-transfer potential

The tendency of an organic molecule to transfer its terminal phosphoryl group to an acceptor molecule.

Oxidative phosphorylation

A process that uses the energy of a proton gradient to produce ATP.

Activated carriers

Small molecules that carry a functional group or electrons and can donate them to another molecule.

NAD+

Nicotinamide adenine dinucleotide, an activated carrier that accepts electrons and protons in redox reactions.

FAD

Flavin adenine dinucleotide, an activated carrier that accepts electrons and protons during substrate oxidation.

Coenzyme A

A carrier of acyl groups, derived from vitamin B5, that plays a key role in the transfer of acyl groups and synthesis.

Energy charge

A measure of the energy state of a cell; it reflects the ratio of ATP to ADP and AMP.

Feedback inhibition

A regulatory mechanism in metabolism where the end product of a pathway inhibits an earlier step.

Energy

Is required for mechanical work muscle contraction and cell movement, active transport, and biosynthesis

Metabolic pathway

A series of linked reactions by which fuels are degraded and large molecules are constructed

• example: glycolysis is a 10-step metabolic pathway converting glucose to pyruvate

• Are interconnected series of enzyme-catalyzed reactions

Themes common to all metabolic reactions

Metabolism is a coherent network containing many common motifs

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

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

• ~100 molecules serve as activated intermediates

• Metabolism uses only a few kinds of mechanisms that are typically simple

• Metabolic reactions are highly regulated because metabolic pathways are interdependent

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

  • Increases speed and efficiency

  • Allows efficient processing of unstable or toxic intermediates

Amphibolic pathways

Pathways that can either be anabolic or catabolic depending on cellular energy conditions

A thermodynamically unfavorable reaction

Can be driven by a favorable reaction

A metabolic pathway must meet 2 criteria

• individual reactions must be specific

• Each of the reactions in the pathway must be thermodynamically favored under real conditions

A reaction can occur spontaneously

Only if ∆G, the change in free energy, is negative.

Overall free-energy change for a chemically coupled series of reaction

Equals the sum of the free-energy changes of the individual steps

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

• In the example, the reactions are coupled by intermediate B

ATP Hydrolysis

Is exergonic

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

The release of free energy from ATP Hydrolysis

Is by the:

• formation of new covalent bonds

• Formation of noncovalent interactions with water

• Increase in entropy

∆G for ATP hydrolysis

Under typical cellular conditions is approx. -50 kJ mol-1

Structures of ATP, ADP, and AMP

Differ only by the number of phosphates

Enzymes

Catalyze the exchange of phosphoryl groups from one nucleotide to another

• some reactions are driven by GTP, UTP, and CTP

Nucleoside monophosphate kinases

Enzymes that phosphorylate nucleoside monophosphates

Nucleoside diphosphate kinase

Enzymes that phosphorylate nucleoside diphosphates

All nucleoside triphosphates

Are energetically equivalent

Are derivatives of ATP

Two important electron carrier (NAD+ and FAD) and the acyl group carrier, coenzymes A

ATP Hydrolysis

Drives metabolism by shifting the equilibrium of coupled reactions

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

The equilibrium constant K′eq at 25°C

reveals the conversion of A to B cannot take place when the molar ratio of B to A is equal to or greater than 1.15 × 10−3.

K′ = [B]eq / [A]eq = e−∆G°′/2.47 = 1.15 × 10−3

Coupling a Reaction with ATP hydrolysis

• Under standard conditions, ∆G°′ of hydrolysis is approximately −30.5 kJ mol−1.

• Coupling the conversion of A to B with ATP hydrolysis renders the formation of B exergonic

• Coupling these reactions under standard conditions changes the equilibrium ratio of B to A.

The high phosphoryl potential of ATP

Results from structural differences between ATP and its hydrolysis products

• phosphoryl-transfer potential is a means of comparing the tendency of organic molecules to transfer a phosphoryl group to an acceptor molecule

• Example: ATP has a higher phosphoryl-transfer potential than glycerol 3-phosphate

• Is explained by its structure

Phosphoryl-transfer potential

The tendency of an organic molecule to transfer its terminal phosphoryl group to water

• example: ATP has a higher phosphoryl-transfer potential than glycerol 3-phosphate

• is an important form of cellular energy transformation

ATP has a high phosphoryl-transfer potential because of:

• orthophosphate (Pi) has greater resonance stabilization than any of the ATP phosphoryl groups

• Electrostatic repulsion of the triphosphate unit

• The entropy of the products of ATP hydrolysis is greater

• ADP and Pi are stabilized due to hydration

Some compounds

Have higher phosphoryl-transfer potential than ATP

• examples: phosphoenolpyruvate (PEP), 1,3-bisphosphoglycerate (1,3-BPG), and creatine phosphate

• These compounds can transfer their phosphoryl group to ADP to form ATP

Compounds with High Phosphoryl-Transfer Potential

Can be used to make ATP from ADP

Standard free energies of hydrolysis of some phosphorylated compounds

ATP has an intermediate phosphoryl-transfer potential among biologically important phosphorylated molecules

• Enables ATP to function efficiently as a carrier of phosphoryl groups

Creatine Phosphate

Serves as a reservoir of high potential phosphoryl groups

ATP in muscle

Sustains contractile activity for < 1 second

Creatine kinase

Catalyzes the regeneration of ATP from creatine phosphate and ADP

∆G°′ of hydrolysis of creatine phosphate

is −43.1 kJ mol−1

The sources of ATP

Change as Exercise Duration Increases, even within the first few seconds

The oxidation of carbon fuels

Is an important source of cellular energy

• ATP is the principal immediate donor of free energy for biological activities, but ATP is limited

• ATP must be constantly regenerated from ADP

Oxidation of Fuel Molecules

Takes place one carbon at a time

• carbon atoms in fuels are oxidized to yield CO2

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

• Electrons are ultimately accepted by oxygen to form H2O

Fats

Are a more efficient fuel source than carbohydrates because the carbon in fats is more reduced

Compounds with High Phosphoryl-Transfer potential

Can couple carbon oxidation to ATP synthesis

Glyceraldehyde 3-phosphate

A metabolite of glucose formed during glucose oxidation

• the C-1 carbon is at the aldehyde-oxidation level and is not in its most oxidized state

Oxidation of Glyceraldehyde 3-Phosphate

Does not occur directly

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

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

Ion gradients across membranes

Provide an important form of cellular energy that can be coupled to ATP synthesis

• the oxidation of fuel molecules or phototrophy produces 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

  • This process is called oxidative phosphorylation

Proton Gradients Formed using the energy from either sunlight or chemical oxidation

Can power ATP synthesis

Phosphates

Play a prominent role in biochemical processes

• __ esters are thermodynamically unstable yet kinetically stable in water

  • Kinetic stability is due to the negative charges that resist hydrolysis in the absence of enzymes

  • Their energy release can be manipulated by enzymes

• The addition of a __ group changes molecule conformation and behavior

• No other ions have the chemical characteristics of __

Energy from Food is Extracted in Three Stages

• Stage 1: large molecules in food are broken down into smaller units

• Stage 2: small molecules are degraded to a few simple units that play a central role in metabolism

• Stage 3: ATP is produced from the complete oxidation of the acetyl unit of acetyl CoA

The extraction of energy from food molecules

By aerobic organisms

Metabolic pathways

Contain many recurring motifs

Activated carriers

Small molecules to which a chemical group or electrons have been added, which can then be donated to another molecule

• frequently act as coenzymes or cosubstrates

• Example: ATP is an activated carrier of phosphoryl groups

NADH

An activated carrier of electrons for fuel oxidation

• fuel molecules transfer electrons to carriers, which then transfer their high-potential electrons to O2

Nicotinamide adenine dinucleotide (NAD+)

Accepts a proton and two electrons in the oxidation of a substrate to form NADH

• the reactive part is its nicotinamide ring

FADH2

An activated carrier of electrons for fuel oxidation

Flavin adenine dinucleotide (FAD)

Accepts two protons and two electrons in the oxidation of a substrate to form FADH2

• the reactive part is its isoalloxazine ring

Structures of the Reactive Compounds of FAD and FADH2

Reveal that electrons and protons are carried by the reactive isoalloxazine ring component

• the isoalloxazine ring is a derivative of the vitamin riboflavin

NADPH

Activated carrier of electrons for reductive biosynthesis

• in most biosynthesis, precursors are more oxidized than the products

  • ATP and reducing power are needed

  • Example: four electrons are needed to reduce a keto group to a methylene group

• __ is the electron donor in most reductive biosyntheses

Coenzyme A (CoA)

Activated carrier of two carbon fragments

• a carrier of acyl groups that is derived from vitamin B5 (pantothenate)

  • The reactive part is its terminal sulfhydryl group

  • Acyl groups are linked to __ by thioester bonds to form an acyl __

  • Acetyl linked to is called acetyl __.

Structure of Coenzyme A

CoA-SH

The transfer of the acyl group

Is exergonic because the thioester is thermodynamically unstable

• The ∆G°′ for the hydrolysis of acetyl CoA has a large negative value.

• Electrons of the C=O bond cannot form resonance structures with the C—S bond that are as stable as those that they can form with the C—O bond

Activated carriers

Illustrate key aspects of metabolism

• kinetic stability allows enzymatic control over the flow of energy

  • NADH, NADPH, and FADH2 react slowly with O2 in the absence 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

Many activated carriers

Are derived from vitamins

Vitamins

Organic molecules that are needed in small amounts in the diets of some higher animals

• must be modified to serve its function

• Most activated carriers that act as coenzymes are derived from __

The B vitamins

Are a diverse group of small, water soluble molecules

Key reactions

Are reiterated throughout metabolism

• the thousands of metabolic reactions can be subdivided into 6 types

Oxidation-reduction reactions

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

  • Examples: oxidation-reduction reactions of the citric acid cycle

Group-Transfer Reactions

Used to synthesize ATP and in signaling pathways, among others

• example: phosphoryl group transfer

Hydrolytic Reactions

Hydrolysis cleaves bonds by the addition of water

• commonly used to degrade large molecules

• Example: hydrolytic cleave of proteins

Carbon Bond Cleavage Pt 1

Can occur by means other than hydrolysis and oxidation

• example: the conversion of the six-carbon molecule fructose 1,6-bisphosphate into two three-carbon fragments during glycolysis

Carbon Bond Cleavage Pt 2

Dehydration is an important subclass

• example: the generation of phosphoenolpyruvate from 2-phosphoglycerate

Isomerization reactions

Rearranges atoms within a molecule

• typically to prepare the molecule for a subsequent reaction

• Example: the conversion of citrate to isocitrate

Ligation Reactions

Forms bonds using free energy from ATP hydrolysis

• example: the formation of oxaloacetate from pyruvate and CO2

Metabolic processes

Are regulated in three principal ways

Metabolic pathways

Must be regulated to create homeostasis (a stable biochemical environment)

Metabolism is regulated by three mechanisms

• altering the amount of enzymes

• Restricting the accessibility of substrates

• Regulating the catalytic activity of enzymes internally or externally

Controlling the amounts of enzymes

• the amount of a particular enzyme depends on both its rate of synthesis and its rate of degradation

• The level of many enzymes is adjusted by a change in the rate of transcription of the genes encoding them

Controlling the accessibility of substrates

Compartmentalization often segregates opposed reactions

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

Controlling catalytic activity

Catalytic activity is regulated allosterically or by covalent modification

• feedback inhibition is an example of allosteric regulation

• Concentrations of allosteric activators and inhibitors can be changed

• Reversible covalent modification can control catalytic rates of enzymes

Energy charge

Proportional to the mole fraction of ATP plus half the mole fraction of ADP

• ranges from 0 (all AMP) to 1 (all ATP)

• ATP-generating pathways are inhibited, and ATP-utilizing pathways are stimulated under conditions of high-energy charge

• Energy charge is maintained within narrow limits (0.90 to 0.95)

• Enzymes regulating these pathways are allosterically inhibited or activated by binding to ATP or AMP

Is a useful concept for understanding how metabolism is regulated