kine 326 final

glycolysis definition and whys its important

a metabolic pathway that breaks down glucose into 2 molecules of pyruvate, producing atp and nadh. anaerobic

why its important:

• supplies quick energy when oxygen is low or demand is high

• connects to both anaerobic (lactate) and aerobic (TCA cycle) pathways

what is glycolysis a key part of

energy production in cells, esp during high intensity or oxygen-limited (anaerobic) conditions

where does glycolysis happen

in the cytosol of the cell, outside of mitochondria

atp yield of glycolysis

• from glucose: net gain of 2 atp per molecule

• from glycogen: net gain of 3 atp per molecule

products of glycolysis

• 2 NADH (can yeild 6 atp when used in mitchondria)

• 2 pyruvate (can go on to become lactate or enter the mitchondria for aerobic metabolism)

2 phases of glycolysis:

1. atp investment phase

   1. consumes 2 atp

   2. glucose is converted to two 3 carbon molecules

2. atp payoff phase:

   1. produces 4 atp, 2 nadh, and 2 pyruvate

glucose definition, source, and in glycolysis

glucose - a simple sugar (monosaccharide) and the primary fuel source for cells

• source:

  • comes from the food you eat (carbs)

  • found in bloodstream as blood glucose

• in glycolysis:

  • enters cells via GLUT 4 transporters

  • first step uses hexokinase to convert it to glucose 6 phosphate (G6P)

  • costs 1 atp in the process

glycogen definition, where its store, in glycolysis, in exercise

glycogen - storage form of glucose, made of many glucose molecules linked together (polysaccharide)

• stored in:

  • liver (for maintaining blood sugar)

  • muscles (for energy during exercise)

• in glycolysis:

  • broken down through glycogenolysis into glucsoe 1 phosephate then converted to G6P

  • skips the atp cost step, so u save 1 atp

  • more effieicient for rapid atp production during high intensity exercise

in exercise:

• short, ntense efforts: muscle taps into glycogen first

• sustained activity: uses blood glucose, then replensished it via liver glycogen

phosphorylase

phosphorylase (from glycogen → glycolysis)

• function: catalyzes the first step of glycogenolysis, breaking down glycogen into glucose 1 phosphate (G1P), which is then converted to glucose 6 phosphate (G6P) for use in glycolysis

• reaction

  • glycogen + pi → glycogen 1 + glucose 1 phosphate

  • then, glucose 1 phosphate → glusoce 6 phosphate (via phosphogulcomutase)

activates by:

• amp (singals low energy)

• ca2+ (release during muscle contraction)

• epinephrine (released during stress/exercise)

notes:

• produces G6P wo consuming atp → making ir more energy efficient than using blood glucose

• supports rapid atp production, esp important during high intesnity exercise

hexokinase

hexokinase (blood glucose → glycolysis)

• function: catalyzes the first step of glycolysis from blood glucose

• formula: glucose + atp → glucose 6 phosphate + adp

• notes:

  • ENDERGONIC reaction (req energy)

  • comsumes 1 atp

  • produces 1 H (contributes to acidosis during intense exercise)

  • G6P concentrations stay very low in msucle to drive this reaction forward

  • helps trap glucose inside the cell by converting it to G6P, which cannot leave the cell

definition: allosteric anzymes

regulatory enzymes whose activity can be inc or dec by binding moelcules (called effectors) at sites other than the active site - allosteric sites

• allosteric activators: enhance enzyme activity

• allosteric inhibitors: dec enzyme activity

• play key roles at rate limited or commited steps in metabolic pathways

allosteric enzymes and actvators and inhibititors in glycolysis: phosphorylase

• phosphorylase (in glycogenolysis)

  • function: breaks down glycogen → glucose 1 phosphate

  • activated by:

    • amp (singals low energy)

    • ca2+ (released during muscle contraction)

    • epinehrine (stress hormone)

  • why? these signals mean the muscel needs nergy fast, so glycogen breakdown must inc

allosteric enzymes and actvators and inhibititors in glycolysis: phosphofructokinase

• phosphofructokinase (PFK) - key regulatory step in glycolysis

  • function: converts fructose 6 phosphate → fructose 1,6 biphosphate

  • inhibited by:

    • high atp - enough energy already

    • low ph (inc in H) - prvents excess acidosis

    • glucagon - hormone that promotes glucose conservation

  • activaed by

    • adp

    • amp (stringest actviatory - signals high energy demand)

allosteric enzymes and actvators and inhibititors in glycolysis: pyruvate kinase

• pyruvate kinase - final step of glycolysis

  • function: converts phosphoenolpyruvate (pep) → pyruvate, producing atp

  • inhibited by:

    • high atp, esp during rest ro light activity

  • activated by:

    • fructose 1,6 bisphosphate - feedforward actviation

allosteric enzymes and actvators and inhibititors: why it matters?

• energy demans (atp/amp ratio)

• hormornal signals (like epinephrine or glucagon)

• exercise intensity (inc H, in ca2+)

atp cost

atp cost (investment phase)

• the first hald of glycolysis, where the cell used atp to initiate the breakdown of glucose

  • hexokinase (-1 atp) - converts glucose → glucose 6 phosphate

  • pfk (-1 atp) - converts fructose 6 phosphate → fructose 1,6 bisphosphate

• total atp cost:

  • from glucose: 2 atp used

  • from glycogen: only 1 atp used (hexokinase step is skipped bc of glycogen enters as G6P)

atp produced

atp produced (payoff phase)

• second hald of glycolysis, where the cell genrates energy

  • glyceraldehyde 3 phosphate steps (x2 per glucose) → atp generating reactions (+4 atp total)

• net atp gain:

  • from glucose: 4 produced -2 used = 2 atp

  • from glycogen: 4 produced - 1 used = 3 atp

NADH net yield:

• glycolysis: also produced 2 NADH (which generate 6 atp later durign aerobic respiration

• each NADH = 3 atp (in mitochondria if o2 is available)

NADH definition

NADH, nicotinamide adenine dinucleotide (reduced from) - an electron carrier that stores high energy electrons to be used later to generate ATP duing aerobic respiration

where is NADH produced in glycolysis?:

in phase 3 of glycolysis (the payoff phase), G3PDH catclyzes the reaction

• glucose + 2NAD + 2Pi+ 2ADP → 2 pyruvate + 2NADH +2H + 2ATP + 2H2O

  • since glucose gives 2 G3P, this step happens twice producing:

    • 2 NADH

    • 2 H+

energy potential of NADH

• aerobic: each NADH can yeild 3 ATP in the mitochondria via the electron transport chain (ETC)

  • 2 NADH = 6 ATP

• anaerobic: (intense exercise) NADH is used to convert pyruvate → lactate via lactate dehydrogenase (LDH)

  • pyruvate + NADH → lactate + NAD(+)

  • this regenerate NAD+, allowing glycolysis to continue

H+ and acidosis:

• H+ producation contributes to acidosis during intense exercise

• but: lactate production actually helps conumes H+, buffer pH and delaying fatigue

• side product of NADH fromation

pyruvate structure, formation, and reaction

• structure: 3 carbon molecule that is the end product of glycosis

• formation: aech molecule of glucose (6 carbon compound) is converted into 2 molecules of pyruvate during glycolysis

  • reaction: glucose + 2NAD + 2Pi+ 2ADP → 2 pyruvate + 2NADH +2H + 2ATP + 2H2O

roles of pyruvate

• roles:

  • energy production

    • aerobic: pyruvate is transported into the mitchondria → further porcessed in the citric acif cycle to generate more ATP

  • enearobic respiration

    • anaerobic: pyruvate can be converted into lactate through the enzyme lactate dehydrogenase. conversion helps regenerate NAD, allowing glycolysis to continue producing atp

  • amino acif synthesis

    • pyruvate is key stating material for the synthesis of non essential amino acids

significance of pyruvate

• pyruvate dehydrogenase deficiency:

  • can lead to metabolic distrubances bc it affects conversion of pyruvate into acetyl CoA

  • limits the ability of cells to use glucose effectively through aerobic respiration

• lactic acidosis:

  • excessive production of lactate from pyruvate

  • coniditions such as oc=xygen deficit or metabolic dysfunction

oxidative phosphorylation definition

final and most ATP rich stage of aerobic cellular respiration

what does oxidative phosphorylation involve

• takes place in mitochondria. invovles:

  • oxidation of nutrients (carbs and fats) to generate high energy electrol carriers: NADH and FADH2

  • use of those electrons in the electron transport chain (etc) to pump H+ ions, creates proton gradient

  • uses that gradient to phosphorylate adp into atp via atp synthesis

  • oxygen acts as the final electron acceptor and combines protons and electrons to form water

where does oxidative phosphorylation happen:

• where does it happen:

  • inside the mitochondrion sepficially:

    • electron transoprt chain is int he inner mtochondrial membrane

    • proton gradient forms between the intermembrane space and matrix

    • atp is synthesized in the matrix

oxidative phosphorylation: flow of energy:

• pyruvate → acetyl-coa

  • pryruvate (from glycolysis) enters the mitochrondria → converted to acetyl-coa by enzyme pyruvtae dehydrogenase (pdf)

• tca cycle

  • acetyl-coa enters tca cycle generating:

    • 3 nadh

    • 1 fadh2

    • 1 atp

    • 2 co2

  • happens twice per glucose molecule (1 glucose → 2 pyruvate → 2 acetyl-coa)

• electron transport chain (etc)

  • nadh donates electrons to complex 1, producing 3 atp per nadh

  • fash2 donates electrons to complex 2, producing 2 atp per fadh2

  • electrons flow through complexes 1-4, and protons (H+) are pumped into the intermembrane space

  • oxygen accepts the electrons at complex 4, forming h2o

• atp synthase

  • H+ flows back into the matrix through atp synthase, powering the ocnversion

    • adp +pi → atp

oxidative phosphorylation: net atp yield

• glucose: 2 atp + 2 nadh → 8 atp

• pyruvate → acetyl-coa: 2 nadh → 6 atp

• tca cycle (2x): 2 atp + 6 nadh + 2 fadh2 → 24 atp

• total: ~38 atp

oxidative phosphorylation: why is o2 crucial

• o2 is crucial bc:

  • wo oxygen, etc backs up, nadh/fadh2 cant drop odd electrons, and atp production stops

  • anerobic ocnditions forces cells to rely on glycolysis alone, producing only 2 atp per glucose

TCA cycle definition

• tca cycle - central metabolic pathway that takes place in the mitochondrial matrix

  • oxidizes acetyl-coa (from pyruvate, fats, or animo acids to produce nadh, fadh2, and atp,

  • used in oxidative phosphorylaition to generate atp

where does acetyl-coa come from

• glucose → glycolysis → pyruvate

• pyruvate → via pyruvate dehydrogenase (pdh) → acetyl-coa

• also from beta oxidation of fats or amino acid metabolism

• per 1 acetyl-coa, the tca cyle produces:

  • 3 nadh → 9 atp

  • 1 fadh2 → 2 atp

  • 1 atp

  • 2 co2

  • total: 12 atp equivalents

purpose of the tca cycle

• fully oxidize acetyl-coa to co2

• generate high energy electron carriers (nadh, fadh2)

• provide precursosrs for amino acid and nucleotide synthesis

connection of tca cycle to etc

the nadh and fadh2 carry electrons to the etc, where most atop is porduced through oxidative phosphorylation

ETC definition and primary job

• ETC - the final step of aerobic respiration, occuring in the inner mitchondrial membrane

  • primary job:

    • transfer electrons from nadh and fadh2 to oxygen

    • use the energy from this transfer to pump protons (H+) and create a proton gradient

    • use that gradient to power atp synthesis

etc components and flow of electrons: complex 1 and 2

1. complex 1 - nadh dehydrogenase

   1. nadh donates electrons

   2. pumps H+ into intermembrane space

   3. 3 atp generated per nadh

2. complex 2 - succinate dehydrogenase

   1. fadh2 donates electrons here

   2. no H+ pumped at this complex

   3. 2 atp generated per fadh2

etc components and flow of electrons: coenzyme q and complex 3

coenzyme Q (ubiquinone)

1. transfers electrons from complex 1 and 2 to complex 3

3. complex 3 - cytochrone bc, complex

   1. accepts electrons and pumps more H+

etc components and flow of electrons: cytochrome c and complex 4

5. cytochrome c

   1. moblie electron carrier between complex 3 and 4

6. complex 4 - cytochrome c oxidase

   1. transfers electrons to oxygen, the final electron acceptor

   2. O2 + 4H(+) + 4e → 2 h2o

   3. pumps additional H+

etc components and flow of electrons: atp synthesis via atp synthase

• H+ flows back into the mitochondrial matrix through ATP synthase it powers:

  • adp p1 → atp

  • process called chemiosmosis

  • atp synthase used the potential energy of the H+ gradient to form ATP

why oxygen is important: etc

• o2 is the terminal electron acceptor

• wo o2 etc backs up → nadh and fadh2 cant unload → tca and glycolysis slows down → energy crisis

fates of pyruvate

after glycolysis, each glucose molecule yeilds 2 pyruvate molecules

• anerobic conditions (no o2) - cytosol

  • pyruvate → lactate

    • enzyme: lactate dehydrogenase (LDH)

    • purpose: renegrates NAD so glycolysis can continue

    • happens during intese exercise when o2 is limited

    • produces no additional atp beyond glycolysis

    • associated with lactic acid build up

• aerobic conditions (w o2) - mitchondrion

  • pyruvate → acetyl-coa

    • enzyme: pyruvate dehdrogenase complex (pdh)

    • reaction: pyruvate + nad + coa → acetyl-coa + nadh + co2

    • occurs in the mitcochondrial matrix

    • acetyl-coa enters the tca cycle for further oxidation

cho oxidation pathway definition

process by which glucose is completely broken down into carbon dioxide and water to produce atp,

cho oxidation pathways

• glycolysis : glucose → 2 pyrvate + 2 atp + 2nadh

  • net atp: 2 atp

  • byproducts: 2 nadh, 2 h2o, 2H

• pyruvate → acetyl-coa:

  • pyruvate transported to mitochondria and converted to acetyl-coa via pyruvate dehydrogenase complex (pdh)

  • per glucose:

    • 2 pyruvate → 2 acetyl-coa + 2 nadh + 2 co2

• tca cycle:

  • acetyl-coa eneters tca cycle, combing w oxaloacetate to form citrate (6C)

  • per glucose (2 turns)

    • 2 acetyl-coa → 6 nadh + 2 fadh2 + 2 atp + 4 co2

• etc

  • nadh and fadh2 donates electrons to etc

  • protons are pumped into intermembrane space, froming proton gradient

  • as h+ flows back into the matrix through atp synthase, atp is generated

  • o2 si final electron acception, froming h2o

  • atp yeild:

    • 2.5 atp per nadh

    • 1.5 atp per fadh2

ATP supply definition

• atp - the energy currency of the cell. your muscles constantly use atp to contract and they have to regenerate it quickly to keep it going.

  • there are 3 main systems that supply atp, depending on intensity, duration, and oxygen availability

3 systems of atp supply

• phosphagen system:

  • use for immediate, explosive efforts (ex. sprints)

  • lasts about 5-10 seconds

  • reaction: pcr + adp → atp + creatine

  • no o2 needed

• glycolytic system

  • used during moderate high intensity, short efforts (30 sec - 2 min)

  • glucose → pyruvate → atp

  • glucose: net 2 atp

  • glycogen: net 3 atp

  • produces lactate in anaerobic ocnditions

  • fast but leads to acid build up

• oxidative

  • dominates during long steady activity (over 2 min)

  • includes:

    • glycolysis

    • pyruvate → acetyl-coa

    • tca cycle

    • etc

  • high atp yeild: 30-38 atp per glucose

  • uses oxygen and is sustainable for endurance

lipolysis

• lipolysis - process of breaking down fat into

  • free fatty acid

  • glycerol

  • happens in adipose tissue and intramuscular fat stores, esp during porlonged, lower intensity exercise

  • enhanced during endurance and fasted states

where lipolysis fits in

• triglyceride (tg) stored in fat → broken down by homrone sensitive lipase (hsl)

• yeilds 3 ffa + 1 glycerol

• ffas enter the bloodstream, bind to albumin, and are transported to muscle

• inside muscle:

  • ffa → activiated to fatty acytl-coa

  • transported into mitochondria via carnitiine shuttle

  • enters beta oxidation → acetyl-coa → tca cycle

fat oxidation

fat oxidation

• happens in the mitochondria

• breaks down long chain fatty acids 2 carbons at a time into acetyl-coa

• produces:

  • nadh

  • fadh2

  • lots of atp

exercise relevance: fat and cho oxidation

• at rest or low intensity, fat is the primary fuel

• as intensity inc, bodys hifts towards cho oxidation due to speed and o2 efficiency

• training inc mitochondrial enzymes and fat oxidation capcity