chapter 3

All living organisms require energy to

• power muscle

• pump blood

• absorbs nutrients

• exchange respiratory gases

• synthesise new molecules

• establish cellular ion concentrations

Energy

• capcity to do work

  • ex. potential & kinetic
    both can be converted from 1 class to the other

• no mass and does not take up space

Potential energy

• energy of position or stored energy

• must be converted to the latter beforehand to do work

• forms

  • chemical energy

• ex

  • glycogen

  • water at top of a dam

  • chemical bonds

  • concentration gradients

  • Na^+ ions (outside cell) in high concentration have _

  • electrons in high-energy shells have ___

Kinetic energy

• energy of motion

• can be harnessed to do work

• forms

  • electrical energy

  • mechanical energy

  • sound energy

  • radiant energy

  • heat

• ex

  • glucose

  • falling water

  • Na^+ ions moving to area of low concentration (inside cell) have __

  • electrons passing from high-energy shells to low energy state

Concentration gradient

• exists across plasma membrane

  • boundary between inside & outside of cell

Chemical energy

• one form of potential energy

• energy stored in a molecule’s chemical bonds, released when bonds are broken

• used for

  • movement, molecule synthesis, establishing concentration gradients

• ex of molecules that function in __ ___ storage

  • triglycerides

  • glucose

  • ATP

• ex. plants convert solar energy to __

Triglycerides

• involved in long term energy storage in adipose connective tissue

Glucose

• stored in liver & muscle tissue in the form of the polymer glycogen

ATP

• used as the energy currency for energy-requiring processes within the cell

• stored in all cells in limited amounts

  • cell cannot stockpile __ so typically only a few secs worth of __ is present

• is produced continuously & used immediately for cells energy requiring proceses

• formed from glucose oxidation/cellular respiration

  • the energy RELEASED from glucose is used to make __ (not broken down)

Electrical energy

• movement of charged particles

  • ex. movement of ions across the plasma membrane of a neuron

Mechanical energy

• exhibited by objects in motion due to applied force

  • ex. muscle contractions for walking

  • ex. pumping action of heart to circulate blood

Sound energy

• molecule compression caused by vibrating object

  • ex. the sense of __ is initiated when __ waves cause vibration of the eardrum (tympanic membrane) in the ear

Radiant energy

• energy of electromagnetic waves

  • ex. visible light striking the retina

Heat

• kinetic energy from movement of atoms, ions, molecules

• usually not available to do work / unusable form of energy / waste product

• accompanies all changes in energy

• measured as the temperature of a substance

Electromagnetic spectrum

• the full range of all types of electromagnetic radiation, organized by frequency or wavelength

• divided into seven main regions, ordered from lowest energy (longest wavelength and lowest frequency) to highest energy (shortest wavelength and highest frequency)

• highest frequency

  • gamma rays > x-rays > UV light > visible light > infared light > radio waves

what part of the electromagnetic spectrum can humans see

• visible light

What has high electromagnetic energy

• gamma rays

• x rays

• UV light

• (range capable of entering the body & damaging DNA, causing mutations)

Electromagnetic waves

• travel at the speed of light in a vacuum / empty space

Thermodynamics

• study of energy transformations

1st Law of thermodynamics

• energy can neither be created nor destroyed, it can only change in form (transformed)

2nd law of thermodynamics

• when energy is transformed, some energy is lost to heat

  • the amount of usable energy decreased

  • ex. moving around to warm up on a cold day

  • as chemical energy converts to mechanical energy, heat is produced

Metabolism

• all biochemical reactions in living organisms

Chemical reactions

• occur when chemical bonds in existing molecular structures are broken

• new bonds formed

• expressed as chemical equation

  • reactants

  • products

  • arrow indicates direction of change

• classified based on 3 criteria

  • changes in chemical structure

  • changes in chemical energy

  • whether the reaction is irreversible or reversible

• classified based on changes in chemical structure

  • decomposition reactions

  • synthesis reactions

  • exchange reactions

Reactants

• substances present prior to start of a chemical reaction

• the substrates

• written on left side of equation

• A + B → C

  • __ would be A & B

  • arrow indicates reaction direction

  • in a balanced equation, # of elements are = on both sides of the reaction

Products

• substances formed by the reaction

• written on right side of equation

• A + B → C

  • __ would be C

  • arrow indicates reaction direction

  • in a balanced equation, # of elements are = on both sides of the reaction

Decomposition reaction (Classification of Chemical Reactions)

• initial large molecule broken down to smaller structures

• AB → A + B

• ex

  • hydrolysis reaction of sucrose into glucose & fructose

• all __ in the body are referred to as catabolism or catabolic reactions

  • release energy

Synthesis reaction (Classification of Chemical Reactions)

• 2 or more structures (atoms, ions, molecules) combined to form a larger structure

• A + B → AB

• ex

  • dehydration synthesis reaction forming a dipeptide

• all __ in the body are referred to anabolism or anabolic reactions

  • require energy input

Exchange reaction (Classification of Chemical Reactions)

• groups (atoms, molecules, ions, electrons) exchanged between 2 chemical structures

  • has both decomposition & synthesis components

  • most prevalent in human body

• AB + C → A + BC

• ex.

  • production of ATP in muscle tissue

  • creatine phosphate + ADP → creatine + ATP

Oxidation-reduction (redox) reaction

• exchange reaction where electrons moved from one chemical structue to another

• OIL RIG

  • structure that loses an electron = oxidized during oxidation (+)

  • structure that gains an electron = reduced during reduction (-)

• reactions always occur together

  • electrons may be moved alone or w a hydrogen ion

• ex. Nicotinamide adenine dinucleotide

  • (NAD^+): oxidized

  • (NADH): reduced

Nicotinamide Adenine Dinucleotide

• energy rich molecule (glucose) is oxidized

  • gives up 2 hydrogen atoms

• NAD^+ reduced to NADH

  • gains both a hydrogen ion & 2 electrons

• energy movement of electrons can be used to do work

Exergonic reactions

• reactants with more energy within their chemical bonds/reactants than products

• energy released with net decrease in potential energy

  • ex

    • decomposition reactions

    • glucose + o2→ co2 + water

    • ATP splitting

Endergonic reactions

• reactants with less energy within their chemical bonds than products

• energy required/ supplied with a net increase in potential energy

• ex

  • synthesis reactions

  • amino acids → dipeptide

  • ATP formation

ATP cycling

• continous formation & breakdown of ATP

• ATP formed when energy is released in exergonic reactions

  • fuel molecules from food are oxidized

  • energy in their bonds transferred to ADP + free phosephate to form ATP

• ATP oxidized to aid energonic reactions

  • energy released from ATP hydrolysis provides energy

• only a few secs worth of ATP present at a time

  • formation of ATP occurs continously to provide energy

Irreversible reacion

• net loss of reactants & a net gain in products

  • chemical reaction is moving forward, using up the starting materials to create new substances

• proceed in only 1 direction (single arrow)

• A + B → AB or AB → A + B

Reversible reaction

• does not proceed only to the right (double arrow)

• A + B ← → AB

• no net change in concentration of either reactants or products / formation of products = formation of reactants = equilibrium

  • increase in reactants or decrease in products drives equation to the right

  • decrease in reactants or increase in products drives equations to the left

• ex.

  • carbonic acid reaction

  • CO2 + H2O ← → H2CO3

  • newly formed carbonic acid is unstable & dissociates to form bicarbonate (HCO3^-) & a hydrogen ion (H^+)

  • CO2 + H2O ← → H2CO3 ← → H^+ + HCO3^-

  • occurs in blood transport of CO2 & maintaining acid-base balance

Driving equation to the right

• Increase Reactants: Adding more starting materials forces the reaction to move forward and use up the extra reactants to make more products.

• Decrease Products: Taking away the finished results forces the reaction to make more to replace what was lost.

• What it means: The reaction accelerates in the forward direction to produce more substances on the __ side of the arrows.

• The result: You consume more reactants and create more products

Driving equation to the left

• decrease in reactants or increase in products

• Decrease in reactants: The system shifts left to make more reactants and replace what was lost.

• Increase in products: The system shifts left to use up the extra products that were added & make more reactants

• What it means: The reaction accelerates in the backward direction to produce more substances on the __side of the arrows.

• The result: You break down products to recreate the original reactants.

Reaction rate

• measure of how quickly a chemical reaction takes place

• determines the amount of product formed per unit of time

• dependent upon the concentrations of both the enzyme, substrate, temp, & pH

Activation energy (Ea)

• energy required to break existing chemical bonds (for the chemical reaction to proceed)

• a primary factor determining reaction rate

• overcoming the __ __

  • in lab, increasing temp provides energy to break bonds

  • significant temp increase in a cell would denature proteins

  • protein catalysts called enzymes are used instead

• ex.

Explain the effect a fever would have on chemical reaction rates within the body. What is the risk to protein structure with a high fever?

• initially speeds up chemical reaction rates in the body by increasing the kinetic energy and collision frequency of molecules. Cellular metabolism and immune responses temporarily become more active to help fight off infection

• denature: the excessive heat disrupts the weak chemical bonds (like hydrogen bonds) holding proteins together. Essential biochemical reactions slow down or stop entirely, which can lead to cellular damage and organ failure

catalyst

• a substance that speeds up a chemical reaction without being changed or used up itself

Enzymes

• protein molecules / biologically active organic catalysts that accelerate chemical reactions

• increase reaction rates by decreasing activation energy (Ea) of cellular reactions

• uncatalyzed: no enzyme present

• catalyzed: enzyme present

• only facilitate reaction that would alr occur

• increase rate of product formation

• most __ are globular proteins

• multiple __ usually required to convet initial substrate to final product

• 6 major funcitonal classes:

  • Transferases

  • Hydrolases

  • Oxidoreductases

  • Isomerases

  • Ligases

  • Lyases

Globular proteins

• spherical, water-soluble protein that performs active metabolic, transport, and regulatory functions in the body

• range in size from small (60 amino acids) to large (2500 amino acids)

• unique 3-dimensional structure in protein chain called active site

• temporarily forms enzyme substrate complex

Active sites specfifity

• permits only a single substrate to bind

• helps catalyze only one specific reaction

Location of enzymes

• some remain within cells

  • ex. DNA polymerase, helps form new DNA

• some become embedded in plasma membrane

  • ex. lactase in walls of small intestine cells helps digest lactose

• some are secreted from the cell

• ex. pancreatic amylase released from pancreas to participate in starch digestion

Mechanism of Enzyme Action

• substrate enters active site, forming enzyme-substrate complex

• enzyme changes shape slightly, resulting in even closer fit (induced fit model)

• change in enzyme shape stresses chemical bonds, permitting new bonds to be formed

• products are released. enzyme may repeat process

Cofactors

• molecules or “helper” ions required to ensure that a reaction occurs

• nonprotein structure thats either organic or inorganic substance

  • inorganic cofactors

    • ex. zinc ion required for carbonic anhydrase to function

  • organic cofactors (carbon-based) called coenzymes

    • ex. vitamins or modified nucleotides serving as coenzymes

inorganic cofactors

• attached to the enzyme

• required for normal function

• ex. zinc ion required for carbonic anhydrase to function

organic cofactors / coenzymes

• carbon based

• not attached to enzymes, still assist them

• ex. vitamins, nucleotides like NAD

cofactors vs coenzymes

cofactor: any non-protein helper molecule that an enzyme needs to function

coenzyme: specific type of organic cofactor

• All coenzymes are cofactors, but not all cofactors are coenzymes

Oxidoreductases (enzyme class)

• redox reactions

• dehydrogenases involved in electron transfer

• ex.

  • dehydrogenases uses NAD^+ or a molecule other than oxygen as electron acceptor

  • peroxidase uses hydrogen peroxide (H2O2) as electron acceptor

Dehydrogenase

• involved in electron transfer

  • participate in redox reactions by moving hydrogen from 1 molecule to a diff molecule

• subcategory of enzymes within the oxidoreductase class

Transferases (enzyme class)

• transfer atoms or molecules between chemical structures

• kinases transfer phosphate groups

• ex.

  • phosphorylase transfers a phosphate (PO4³-) to a diff substance

  • kinase transfers a phosphate (PO4³-) usually from ATP to a diff substance

Kinases

• transfer phosphate groups (usually from ATP to another molecule)

• specific subgroup of transferases

Hydrolase (enzyme class)

• split chemical bonds using water

• ex.

  • phosphate removes phosphate

  • protease digests proteins

  • lipase splits lipids (triglyceride)

  • sucrase splits sucros

Isomerases (enzyme class)

• covert one isomer to another

• ex

  • mutase transfers atoms within a molecule

Ligases (enzyme class)

• bond 2 molecules together

• ex

  • synthetase bonds 2 molecules using ATP

Lyases (enzyme class)

• split bonds without using water

• ex

  • decarboxylase cleaves a molecule to release co2

  • synthase catalyzes a synthesis process

Naming of enzymes

based on

• name of substrate or product or type of chemical reaction

• subclass

• suffix: -ase

  • ex.

  • pyruvate dehydrogenase transfers hydrogen from pyruvate

  • DNA polymerase helps form DNA

  • lactase digests lactose

Rate of a chemical reaction may be accelerated by

• increase in enzyme concentration

• increase in substrate concentration

  • increases only up to the point of saturation (so much substrate is present that all enzyme moloecules are engaged in reaction)

Effect of temp on enzymes

• 3-dimensional shape of enzymes dependent on temp

• human enzymes function best at optimal temp (usually 40C, 104F)

• moderate fever

  • results in more efficient enzyme activity

• severse increase in temp

  • cause protein denaturation w loss of function

Enzymes & pH

• enzymes function best at optimal pH

• between pH of 6-8 for most enzymes

• changes in H^+ disrupt electrostatic interactions

• enzyme loss of shape, denaturation

• optimal pH may diff

  • ex. enzymes working in the lower pH of the stomach

Inhibitors

• bind enzymes & turn them off

• prevents overproduction of product

• later release of inhibitor allows enzyme to function again

• inhibitors can be competitive or noncompetitive

Competitive inhibitor

• resembles substrate & binds to active site of enzyme

• compete for occupation of active site

• with greater substrate

  • less likely competitive inhibitor will occupy site

• with less substrate

  • more likely inhibitor will occupy site

Noncompetitive inhibitor / allosteric inhibitors

• do not resemble substrate

• bind a site other than active site (allosteric site)

• induce conformational change to enzyme & active site

  • makes it so that substrate cannot bind to enzyme

• not influenced by concentration of substrate

Metabolic pathways

• connected chains of chemical reactions inside a cell that change a starting molecule into a final product

  • using a series of enzymes

• product of one enzyme becomes substrate of the next

  • regulated by negative feedback to maintain the needed amount of the final product

• ex. chemical breakdown of glucose

  • forms ATP, the “energy currency” of cells

  
  

Multienzyme complex

• group of attached enzymes

• work in a sequence of reactions to convert substrate → final product

• physically attached to each other through noncovalent bonds

• ex. pyruvate dehydrogenase involved in breakdown of glucose

• advantages

  • since the product of one reaction is passed directly to the next enzyme in the complex, its less likely substance will diffuse away into diff biochemical pathway

  • single complex can be regulated rather than individual enzymes

• pathways regulated through negative feedback

  • product from metabolic pathway acts as an allosteric inhibitor

    • turns off enzyme early in pathway

    • as more product accumulates = the pathway is slowed or shut down = leading to less product formed

    • as less product accumulates = inhibition is lifted = more product formed

Phosphorylation

• addition of phosphate group

• performed by phosphorylases or kinases

• turns on some enzymes, turns off others

Dephosphorylation

• removal of phosphate group

• performed by phosphatases

• turns on some enzymes, turns off others

Drugs as enzyme inhibitors

• drugs increase or decrease specific enzyme activity

• ex

  • penicillin targets a bacterial enzyme, slowing spread of infection

  • sildenafil (viagra) inhibits phosphodiesterase type 5

    • treats erectile dysfunction by vasodilation of blood vessels of the weewee

Lactose intolerance

• caused by a deficiency in lactase or abnormal lactase

  • lactase is required to break down lactose into glucose & galactose

• common in older adults

• symptoms: abdominal upset, nausea, diarrhea, bloating, gas

• treatment: lactase enzymes, avoidance of milk, or drinking lactose-free milk

How do changes in substrate concentration, temperature, and pH affect the reaction rate of enzyme-catalyzed chemical reactions?

Substrate Concentration

• Low concentration: The reaction rate is slow. Molecules bump into each other less often.

• Increasing concentration: Adding more substrate makes molecules collide more often. This speeds up the reaction rate.

• Saturation: When all enzyme active sites are full, the reaction rate stops rising. It reaches a maximum speed. More substrate cannot make it go faster because no free enzymes are left

Temperature

• Low temperature: Molecules have low kinetic energy (movement energy). They move slowly, collide rarely, and have a low reaction rate.

• Rising temperature: Warming up the mixture gives molecules more energy. They collide more often and react faster.

• Optimum temperature: This is the best temperature where the reaction rate is highest (usually around 37°C for humans).

• High temperature (Denaturation): Past the best temperature, too much heat breaks the bonds holding the enzyme together. The active site changes shape. The substrate no longer fits, and the reaction rate drops fast

pH (Acidity)

• Optimum pH: Each enzyme works best at a specific pH level, called the optimum pH. For example, stomach enzymes like acidic conditions (low pH), while most other body enzymes prefer a neutral pH around 7. [1, 2]

• Extreme pH (Denaturation): If the pH is too high or too low, it changes the electrical charges of the amino acids in the enzyme. This breaks the protein's internal bonds. The active site warps, the substrate cannot bind, and the reaction rate decreases. [1, 2, 3, 4]

The Role of Negative Feedback in Enzyme Regulation / Feedback inhibition

• a self-regulating control system where the final product of a pathway slows down or turns off an enzyme involved earlier in that same pathway

• Noncompetitive inhibitors fit this role because the end-product binds to a separate allosteric site on the enzyme rather than the active site.

• occurs when a plentiful end product binds to an enzyme’s active site, which prohibits substrate binding & inactivates the metabolic pathway

What two processes involve phosphate and are commonly used to regulate enzymes in a metabolic pathway or a multienzyme complex?

• Phosphorylation: Adds a phosphate group to an enzyme, typically using [ATP]. This step is catalyzed by enzymes called kinases. It can turn an enzyme's activity on or off

• Dephosphorylation: Removes the phosphate group from the enzyme. This step is catalyzed by enzymes called phosphatases. It reverses the effect of the kinase, returning the enzyme to its original state

Cellular Respiration

• exergonic multistep metabolic pathway

• organic molecules oxidized & disassembled by a series of enzymes

• potential energy in chemical bonds released (in glucose, fatty acids, amino acids)

  • energy used to synthesize ATP (which is an endergonic process)

• oxygen required for maximum ATP production

• involves at least 20 diff enzymes (located cytosol & mitochondria)

Glucose oxidation

• step-by-step breakdown of glucose with energy release for the synthesis of ATP

  • glucose: energy-rich molecule with many C—C, C—H, C—O bonds

• products: co2 & water

• net chemical reaction: C6H12O2 + 6O2 → 6CO2 + 6H2O

  • (+ 30 net ATP (38 total) released through energy of broken bonds)

  • so __ is broken down into carbon dioxide & water

cellular location

• 20 diff enzymes required

• enzymes found in both

• cytosol: semifluid cell contents of the cell

• mitochondria: small cellular organelles

Pathways for ATP production

• energy from broken bonds used to attach phosphate group to ADP

• energy can be used directly

  • least common

  • substrate-level phosphorylation

• energy can be used indirectly

  • most common

  • energy first released to coenzymes, then energy transferred to form ATP

  • oxidative phosphorylation

Glucose oxidation

• occurs within cells through cellular respiration

• step by step breakdown of glucose w energy release (to synthesize ATP)

• CO2 & water formed

• net chemical reaction: C6H12O2 + 6 O2 → 6 CO2 + 6 H2O

Substrate-level phosphorylation

• ATP produced DIRECTLY

• least common

• a metabolic process that creates ATP (adenosine triphosphate) or GTP by directly transferring a phosphate group from a reactive intermediate molecule to ADP or GDP (from energy directly released from a substrate)

• occurs during glycolysis & citric acid cycle

• no membrane, channel, ETC, It does not use proton gradients or ATP synthase

• works in aerobic (with oxygen) and anaerobic (without oxygen) conditions.

Cellular respiration/ Glucose Oxidation proceeds in 4 stages

• Glycolysis

• Pyruvate oxidation / intermediate stage

• Krebs cycle (aka Citric Acid cycle)

• Electron Transport Chain (ETC)

Good People Keep Empathy

What stages of glucose oxidation require oxygen

• intermeditate stage

• citric acid cycle

• ETC

Glycolysis

• metabolic process

• “sugar splitting”

  • glucose (initial substrate) → 2 pyruvate molecules

• occurs in cytosol

• doesn’t require oxygen

• 10 enzymes in cytosol participate

• regulated through negative feedback

  • ATP acts as an allosteric inhibitor to “turn off” PFK

• conversion of fructose to fructose 1,6-diphosphate

• conversion of glucose to glucose 6-phosphate

• conversion of pyruvic acid to lactic acid (if lack of oxygen)

  • lactate produced

    • to regenerate NAD^+ so this stage can continue

• Oxidized: the 6-carbon sugar glucose

• Reduced: NAD^+ → NADH

• Product: 2 pyruvate molecules

• Net product: 2 ATP (2 invested, 4 formed) & 2 NADH (per glucose)

Glycolysis Steps

steps 1-5

• glucose split into 2 molecules of G3P (glyceraldehye 3 phosphate)

• 2 ATP “invested” at steps 1 & 3

• phosphate groups transferred to break down products of glucose

  • kinase enzymes transfer P from ATP to glucose & the breakdown products of glucose

steps 6-7

• occur 2x in glucose oxidation

• step 6: unattached Pi added to substrate, 2 hydrogen atoms released to NAD^+ to form NADH

• step 7: Pi transferred to ADP to form ATP

steps 8-10

• occur 2x in glucose oxidation

• step 8: molecule from step 7 converted to an isomer

• step 9: loss of water molecule

• step 10: Pi transferred to ADP to form ATP

Simplified

1. 2 ATP donates 2 phosphates (one each) to a glucose, which then becomes 2 ADP

2. Glucose (6 carbon molecule) splits into two 3 carbon molecules each containing 1 phosphate group

3. Each phosphate group is removed from the 3 carbon molecules, which produces 2 ATP for each so 4 total

4. During the process of removing the phosphate group, an electron is stored in a molecule called NADH (2 of them), which was orginally NAD^+

• when NAD^+ takes on an electron (reduced), it becomes NADH

Regulation of glycolysis

• through negative feedback

• ATP acting as allosteric inhibitor to “turn off” phosphofructokinase (PFK)

  • as ATP increases, PFK inhibited

Phosphofructokinase

a vital enzyme that controls the speed of glycolysis

Fate of pyruvate depends on…

• oxygen availability

• if sufficient o2 available = pyruvate enters mitochondria

• if insufficient o2 available = pyruvate converted to lactate

Fate of Pyruvate with insufficient oxygen

1. activity of ETC decreases

   • lvls of NADH & FADH2 accumulate

   • decreased levels of NAD^+ & FAD

2. cell becomes more dependent upon glycolysis

   • requires NAD^+ to continue

3. glycolysis eventually shuts down

   • due to lack of NAD^+

4. NAD must be regenerated for glycolysis to continue

Other fuel molecules that are oxidized in cellular respiration

fatty acids

• enzymatically change 2 carbons at a time to form acetyl CoA: beta oxidation

• acetyl CoA enters pathway at citric acid cycle

• can only be oxidized aerobically

amino acids

• diff pathway if protein is used for fuel

• point of entry depends upon specific type

• amine group is a waste product

  • converted to urea

  • excreted by kidneys

• basically glucose, fatty & amino acids can be used to generate ATP

Mitochondrion structure

• double membrane organelle

  • inner membrane has folds called cristae

• space between membranes is the outer compartment (fluid filled)

• innermost space is the matrix

  • multienzyme complex of intermediate stage resides here

  • enzymes of citric acid cycle reside here

• molecules of ETC system embedded in cristae

Intermediate stage / Pyruvate oxidation

• aerobic process (requires oxygen)

  • pathway is inhibited without it

• occurs in mitochondria (matrix)

• substrate: pyruvate (2) (becomes oxidized)

• multienzyme complex: catalyzed by pyruvate dehydrogenase

  • pyruvate + coenzyme A (CoA) = acetyl CoA

• during decarboxylation, a carboxyl group is released from pyruvate as 1 CO2

  • energy released during this as 2 hydrogen atoms (2 electrons + 2 hydrogen ions) and NAD^+ → NADH (becomes reduced, energy released)

  • Acetyl CoA enters citric acid cycle

Product

• 1 cycle = 1 Acetyl CoA, 1 CO2

• 2 cycles = 2 Acetyl CoA, 2 CO2 (waste product)

Net product

• 1 cycle = 1 NADH

• 2 cycles = 2 NADH

Intermediate stage / Pyruvate oxidation Steps

1. Decarboxylation (Remove CO2): A carboxyl group is removed from pyruvate, releasing CO2

2. Oxidation (Create NADH): The remaining two-carbon fragment is oxidized (acetate), and the electrons are transferred to NAD^+ forming NADH (reduced)

3. Formation of Acetyl CoA: The oxidized two-carbon acetyl group attaches to Coenzyme A, forming Acetyl CoA.

Citric Acid Cycle (Krebs cycle)

• aerobic process (requires oxygen)

  • without it pathway is inhibited

• occurs in mitochondria (matrix)

• substrate: Acetyl CoA (2 from each glucose)

  • oxidizes acetyl-CoA to harvest high-energy electrons

• cyclic metabolic pathway

• 9 enzymes in the mitochondrial matrix

• Acetyl CoA (initial substrate)→ 2 CO2

  • CoA released

• conversion of malic acid to oxaloacetic aid

  • oxaloacetic acid invollved in 1st step & regenerated in last step

• conversion of citric acid to isocitric acid

• by the end of this all 6 carbon atoms originally present in one glucose molecule are fully oxidized and liberated as 6 CO2 molecules

Product

• 1 cycle = 2 CO2 (per acetyl CoA)

• 2 cycle = 4 CO2

Net product

• 1 cycle = 1 ATP, 3 NADH, 1 FADH2 (per acetyl CoA)

• 2 cycles = 2 ATP, 6 NADH, 2 FADH2

Citric Acid Cycle steps

1. Acetyl CoA + oxaloacetate = citrate

2. & 3: Isomer formed by removing a water molecule, then reattaching elsewhere

4. & 5: Transfer of hydrogen to NAD^+ to form NADH; CoA attached

6. Removal of CoA & the formation of ATP (through substrate-level phosphorylation)

7. Dehydrogenase transfers hydrogens to FAD to form FADH2

8. Water removed

9. Dehydrogenase transfers hydrogen to NAD to form NADH; oxaloacetate regenerated

Simpler

1. Oxaloacetate (OAA) is a vital 4-carbon molecule (C4H4O5) reacts with acetyl-CoA to initiate energy production and creates citrate (6 carbon)

2. Coenzyme A is released and recycled to deliver more acetate

3. the acetyl group's two carbon atoms is oxidized to two molecules of carbon dioxide (CO2)

   • the electron carriers 3 NAD^+ and 1 FAD are reduced (gain electron) to 3 NADH and 1 FADH2 (per turn of the cycle)

     • Each molecule in the CAC is less energetic than its predecessor

Dehydrogenase

• an enzyme that helps speed up chemical reactions by removing hydrogen atoms from a molecule and transferring them to another substance

Regulation of the citric acid cycle

• occurs at 1st step enzyme (citrate synthase)

• if energy demands high (cell working hard)

  • lvls of NADH, ATP, & pathway intermediates low

    • bc cell is using it up faster than it can make them

  • cycle activity increased

    • citrate synthase, switches into high gear to speed up the cycle and crank out more energy.

• if energy demands low (cell at rest)

  • lvls of NADH, ATP, & pathway intermediates high

    • substances start piling up in storage, indicates cellular energy demands are low

  • decreased activity of the citrate synthase & citric acid cycle

    • ATP and NADH molecules bump into the enzyme citrate synthase and clog it up (a process called negative feedback inhibition).

• these adjustments maintain homeostasis

citrate synthase

• Catalyzes a Key Reaction: It joins a molecule of acetyl-CoA with oxaloacetate to create citrate and coenzyme A.

• Controls the Pace: It acts as the rate-limiting, pace-making switch that determines how fast the cell processes energy.

Citric acid

• hydrogen ion + citrate

ATP synthase

• membrane enzyme that uses the potential energy in a proton (H^+) gradient to produce ATP / uses an electrochemical gradient of hydrogen ions

  • uses the energy of a proton gradient to add a phosphate to ADP (ADP + P = ATP)

• enzyme complex that admits protons through a membrane, triggering the production of ATP

• location: inner mitochondrial membrane (cristae)

Electron Transport Chain (ETC)

• set of proteins which collectively extract the energy from reduced coenzymes (NADH, FADH2) to form ATP

• occur in mitochondria, witthin inner membrane (cristae)

• series of redox reactions

• require oxygen

• function: transfer of electrons from NADH & FADH2, energy used to make ATP

• oxidation of NADH at enzyme complex 1

• establishment of a chemiosmotic gradient in the intermembrane space

• structures:

  • H^+ pump / ion gradient

    • proteins that transport H^+ from matrix to outer membrane compartment

      • against/up their concentration gradient (active transport, low to high)

      • more H^+ in outer compartment than in matric

    • as electrons are “falling” & passed through the ETC, kinetic energy harnessed by H^+ pumps

      • by ATP synthase to form ADP & Pi into ATP through oxidative phosphorylation

    • move H^+ from matrix to outer compartment maintaining H^+ gradient

  • electron carriers

    • transport electrons between H^+ pumps

  • oxygen is the final electron acceptor

    • electrons combine with H^+ and oxygen to form water

Product: H2O (byproduct) & net ~30 ATP (38 total max, 26 from etc)