CELLULAR RESPIRATION

INTRODUCTION
- Heterotrophs  energy in food made available to cells in usable form  metabolism

OVERVIEW OF METABOLISM
- all various chemical processes which food is utilized
- provide energy for energy, growth of substances, cell repair
- many specific metabolic pathways, each requires diff enz

1. Catabolism
- breakdown / degeneration of absorbed food substances into simpler, smaller molq
- release egy needed to drive cellular func
- give rise to small organic molq  metabolites  building blocks for biosynthesis

2. Anabolism
- biosynthesis of complex molq from simple compounds  requires egy generated
from catabolism
- synthesize polymers (starch / glycogen)  store egy, growth, repair

ATP
- efficient linking / coupling of exergonic catabolism & endergonic anabolism
- specific molq conserve egy derived from exergonic rxns, release it when egy is
needed
- ATP  phosphorylated cpd, significant in most cellular egy transactions

1. Structure
- nucleotide  aromatic base adenine, 5 C ribose, 3 phosphate grps
- phosphate grps linked to each other by phosphoanhydride bonds
- linked to ribose by phosphodiester bond
- 1 phosphate grp attached to C 5 of ribose  adenosine monophosphate
- 2 phosphate grps  adenosine diphosphate
2. Usefulness
- ATP molq serves as intermediate in cellular egy metabolism
- Most egy (30.6 kJ/mol) released when phosphoanhydride bond that links terminal
phosphate to 2nd phosphate undergoes hydrolysis

-
- ATP/ADP system  reversible means of conserving, transferring, releasing egy
- Catabolic processes in cell energy liberating, drives formation of ATP from ADP
- Egy from ATP hydrolysis  provides driving force for essential life processes
- Biosynthesis, active transport, muscle contraction, calvin cycle, nitrogen fixation,
bioluminescence

3. Methods of Forming
Substrate Level Phosphorylation Oxidative Phosphorylation
Process Phosphorylation of ADP / other Enzymatic endergonic
nctd with 5’ diphosphate phosphorylation of ADP to ATP by
Dephosphorylation of organic ATP synthase
substrate Coupled to exergonic e- transport
from substrate to final e- acceptor:
molecular O2
Exergonic passage of protons along
a proton / electrochemical grad
Occurrence During glycolysis in cytoplasm During ETC in inner mitochondrial
During Krebs cycle in membrane
mitochondrial matrix Dependent in membrane integrity
No memb required
Products Small amt of ATP Almost 90% of any ATP generated
in respiration

BIOLOGICAL OXIDATION OF ORGANIC COMPOUNDS

-
Reaction Function
Redox Reactions involve
1. Removal / addition of H
2. removal / addition of e-
Decarboxylation Removal of C atoms from compound to form CO2
Only H from glucose is needed, C removed by decarboxylation, CO2
released as waste material

1. Coenzymes in Biological Oxidations

- small molq  function along with enz, carriers of e- / small func grps
- most common : NAD (nicotinamide adenine dinucleotide) & FAD (flavin adenine
dinucleotide)
- upon reduction, NADH & FADH2  reservoirs of e- and protons from ATP via
oxidative phosphorylation
- NAD / FAD + H+ + e-  NADH / FADH2

2. Glucose as Important Oxidizable Substrate

a) Excellent Fuel
- breakdown of 1 glucose molq releases enough egy to form 36-38 ATP in presence of
O2

b) Versatile Precursor
- intermediates formed by glucose breakdown can be used in many biological rxns

3. Effect of O2 on Glucose Catabolism

- obligate aerobes  must have O2
- obligate anaerobes  must NOT have O2
- facultative anaerobes  can function both aerobically & anaerobically

a) Presence of O2
- aerobic respiration / cellular respiration
- complete ox of glucose to CO2 and H2O
- yields max ATP (36-38)

b) Absence of O2
- anaerobic respiration / fermentation (lactic acid fermentation, alcohol fermentation)
- incomplete ox of glucose
- 2 ATP molq

GLYCOLYSIS
- glucose metabolism always begins with glycolysis (aerobic /
anaerobic)

1. Overview
Location Cytoplasm of all cells
Metabolism Catabolic pathway, 6C glucose split into 2 3C molq
Rearranged to form 3C compound pyruvate (ionized form of pyruvic
acid)
Both SLP (ADP  ATP) and dehydrogenation (NAD  NADH)
For glycolysis to continue at constant rate both ATP & NADH must be
regenerated to NAD & ADP at rate they are produced
Major Phases 1. Energy Investment Phase
- ATP utilization
2. Energy Payoff Phase
- ATP formation
Substrates Glucose / other hexose sugars
 ADP
Inorganic phosphates (Pi)
NAD
Products 2 molq of pyruvate
2 ATPS (net gain)
2 NADH
Water (waste product)
ATP 2 ATPs by SLP
Generation supplies energized e- in form of reduced NAD  directly drive most
ATP production by oxidative phosphorylation

2. Detailed Look
a) Energy Investment Phase
i. Activation of Glucose (Step 1-3)
- conversion of unphosphoryated glucose to phosphorylated fructose 1,6 –
bisphosphate
- hydrolysis of 2 ATPs to provide phosphate grps & egy driving force
- step 3  rate limiting step of glycolysis, involve enz phosphofructokinase

ii. Cleavage / Lysis (Step 4-5)

- cleavage of fructose 1,6-bisphosphate to 2 3-C sugars (dihydroxyacetone &
glyceraldehydes-3-phosphate G3P)
- dihydroxyacetone converted to G3P to produce 2 G3P molq per glucose

b) Energy Payoff Phase

i. Reduction of NAD / Dehydrogenation (Step 6)
- G3P oxidized (dehydrogenation) & NAD reduced to NADH
- 1 NADH supplies 2 energized e- that directly drive most ATP production by
oxidative phosphorylation at inner mitochondrial memb

ii. Substrate Level Phosphorylation (Step 7-10)

- coupled to dephosphorylation of organic substrate
- directly produces 4 ATPs per glucose, overall net gain of 2 ATPs

c) Flowchart
 d) Summary of Glycolysis
- 2 molq of ATP initially invested in steps 1-3, 2 returned to phosphorylation event
(step 7)
- 2 ATP formed per glucose, overall pathway written as:
- Glucose + 2 NAD + 2 ATP + 2 Pi  2 Pyruvate + 2 NADH + 2 H+ + 2 ATP

3. Importance
- glucose is vital source of egy  only catabolic rxn that occurs in abs of oxygen
- for mammalian red blood cells (no memb bound organelles)  only means of ATP
formation
- during exercise, striated muscles receive insufficient O2 to saturate tissures 
aerobic generation of ATP is curtailed, increase in rate of glycolysis
- supplies cells with essential biosynthetic precursors  in liver, provides precursors
for molq it synthesizes (fats, cholesterol, bile acids, plasma
prot)
- once liver glycogen reserves full, carbo converted to fat 
glycolysis supplies initial steps of fat biosynthesis with
substrate rather than source of ATP
- micro-organisms (E.coli, yeast growing on carbo)  both
egy & biosynthesic precursors obtained from glycolysis

4. Regulation
- Phosphofructokinase (step 3)  allosteric enz with
receptor sites for specific inhibitors & activators 
inhibited by ATP
- Phosphofructokinase stimulated by AMP (which cell
derives from ADP)
- As ATP accumulates, inhibition of en slows down
glycolysis  becomes active when ATP becomes ADP (&
AMP) faster than ATP is being regenerated
- Sensitive to citrate (1st pdt of Krebs)  citrate accumulates in mito, some of it passes
into cytosol & inhibits phosphofructose kinase

AEROBIC RESPIRATION

a) What it Is
- occurs in every living ell, only way cell can obtain egy in usable form
- series of enz-catalysed redox reactions  respiratory substrates completely oxidized
to CO2 & O2 reduced to H2O  series of enz controlled rxns  much higher ield of
ATP
- some egy lost as heat

b) Main Stages
Stage Details Location
Glycolysis Occurs in both aerobic & anaerobic Cytoplasm
conditions
Aerobic  pdts of glycolysis proceed
to Krebs cycle and ETC
Link Reaction Occurs only under aerobic conditions Mitochondrial
Pdts  1 H carrier, proceeds to ETC matrix
and acetyl CoA (starting substrate for
Krebs cycle)
Krebs Cycle / TCA Occurs only under aerobic conditions Mitochondrial
Pdts – H carriers, proceed to ETC matrix
Oxidative Phosphorylation Occurs only under aerobic conditions Mitochondrial
Coupled to ETC membrane
Pdts – most of max 36-38 molq of ATP

1. Mitochondria
- localization of mito in cell 
clustered in regions with most intense
metabolic activity, greatest need for
ATP
- muscle cells  mito organized in
rows along fibrils responsible for
contraction

Components Roles
Outer Memb Freely permeable to ATP / ADP / sucrose
Inner Memb Selectively permeable memb
Highly folded to form cristae  increase SA for ETC
Not permeable to NADH, prots for transporting anions & ATP & ADP
Contains members of ETC & ATP synthase complex (stalked particles)
Matrix Site of Link Rxn (LR), Krebs Cycle (KC)
 2. Link Reaction (Between Glycolysis and TCA)
- if molecular O present, pyruvate enters mito, enz of Krebs cycle complete oxidation
of organic fuel
- pyruvate first converted to acetyl CoA through oxidative decarboxylation
- 1 C of pyruvate liberated as CO2 (decarboxylation) , 2 e- and 1 proton removed from
substrate (oxidation)
- transferred to co-enz NAD  NADH
- occurs in mito matrix, catalyzed by pyruvate dehydrogenase
- 1 CO2 removed, 1 NADH formed, co-enz A added to form acetyl
CoA per pyruvate molq
3. Krebs Cycle (TCA)
- begins with entry of acetate in form of acetyl CoA
- with each round of Krebs, 2 C atoms enter in organic form (as acetate), 2 C leave in
inorganic form (as CO2)

a) Overview
Location Mito matrix of all cells (plants & animals)
Metabolism Catabolic pathway, occurs 2x for every glucose
Completes glucose breakdown & oxidation by 8 enzyme controlled steps
Crucial Reactions 1. Oxidative Decarboxylation Acetyl CoA  CO2 (step 3-4)
2. SLP Direct net pdtn of 2 ATP molq per
glucose (step 5)
3. Production of Reduced 3 NADH produced (steps 3,4,8)
Coenzymes 1 FADH2 produced (step 6)
process linked to production of
ATP by oxidative phosphorylation
Cyclic Property Acetyl grps not oxidized directly, only after being covalently added to
large molq oxaloacetate
Regenerated at end of 1 earn of cycle to receive more acetyl grps
Breakdown of multiple metabolic intermediates  lipids, aa, carbo enter
TCA at various steps
Various cpds in cycle can be siphoned off form formation of chlorophyll,
aa etc  TCA is centre for metabolic interconversions
Substrates Acetyl CoA / other intermediates in pathway
ADP
Inorganic phosphates (Pi)
NAD, FAD
Products Per glucose molq (2 turns of cycle)
1. 2 ATP
2. 2 FADH2
3. 6 NADH
4. 4 CO2
ATP Generation 1. 2 ATP by SLP
2. supplies energized e- in form of NADH & FADH2 that directly drive
most ATP production by oxidative phosphorylation in ETC
- after glycolysis catabolizes glucose to produce pyruvate, pyruvate that enters
mitochondrion oxidized to form acetyl CoA in Link Rxn
- acetyl CoA oxidized in series of rxns (TCA)  2 C acetyl grp of acetyl CoA
combines with 4 C molq oxaloacetate to form 6 C citrate
- citrate goes through seq of e- yielding oxidation rxns, 2 CO2 molqs split off,
regenerating oxaloacetate
- in each turn of Krebs, new acetyl grp replaces 2 CO2 molq lost, more e- extracted &
transferred to NAD & FAD to form NADH & FADH2
- e- carriers carry e- to ETC, exergonic passage of e- drives chemiosmotic synthesis of
ATP by oxidative phosphorylation

b) Detailed Look
i. Diagram

c) Overall Budget for Aerobic Respiration

CO2 ATP (SLP) NADH FADH2
Glycolysis - 2 2 -
Link Reaction 2 - 2 -
Krebs Cycle (Twice) 4 2 6 2
Total 6 4 10 2

4. ETC System
- process of coenzyme reoxidation by transfer of e- to O  e- transport
- 4th stage of aerobic respiration
- ETC & OP (oxidative phosphorylation) functionally linked by electrochemical proton
grad that is result of e- transport, source of egy that drives ATP synthesis

a) Overview
Location Inner mito memb (cristae)
Crucial Reaction Energy released from glycolysis & Krebs cycle (stored in NADH &
FADH2) used to drive ATP synthesis
ATP Generation No ATP directly generated
Egy from e- carried by NADH used to pump H+ across inner mito
memb to inner mito memb
Flow of protons back into matrix through ATP synthase allows for
ATP synthesis by oxidative phosphorylation

b) Components
- ETC is embedded in inner mito memb, comprises seq of e- carriers that
can be reversibly reduced & oxidized as e-  temporarily accommodate
1 or 2 e- within molecular struct
- Flavoproteins  flavin mononucleotide (FMN), a coenzyme
- Ubiquinone / coenzyme Q  conenzyme that can carry H+ and e-
- Cytochromes (metalloproteins)  impt cytochromes in ETC:
cytochromes b, c, a, a3 (cytochrome b in diagram)

c) Function
- coenzymes + cytochromes in ETC + enzymes +
essential factors  functional groups /
complexes
- 4 main complexes (I – IV)
- various e- carriers in ETC have differing
reduction potentials  each subsequent
member of ETC has greater affinity of e-
- members of ETC accept e- from NADH,
FADH2, oxidized co-enz NAD & FADS are
regenerated as e- acceptors for participation in
glycolysis & TCA cycle again
- e- eventually passed to final e- acceptor in
molecular O2 (diffused into mito)
- O2 reduced in mito matrix to produce 1 molq
of H2O
-
d) Importance
- ETC generates proton grad across inner mito memb for subsequent oxidative
phosphorylation
- Regenerates NAD & FAD  link rxn & Krebs cycle can continue
- In abs of O2, e- not passed down ETC & no NAD / FAD regenerated)  link rxn &
Krebs will cease

5. Oxidative Phosphorylation
a) Generation of Proton Gradient – Chemiosmotic Coupling Model
- egy released during e- transport  generate electrochemical prot gradient  drive
ATP synthesis
- exergonic transfer of e- through ETC is accompanied by uni-directional pumping of
protons across inner mito membrane into intermembrane space
- creates proton motive force (PMF)  potential egy stored in proton grad
- e- pass along chain of specialized e- acceptor & donor molq in ETC, fall to
successively lower egy states, releasing egy
- egy released drives proton pumps (in inner mito memb) to actively move H+ across
inner mito memb from mitochondrial matrix to intermembrane space
- generates electrochemical proton grad with 2 components
- conc grad of H+ / chemical / pH grad
- electrical gradient  voltage across memb
- build up of H+ conc in intermembrane space,
tendency for H+ to go back into matrix due to
PMF
- inner mito memb impermeable to H+, protons can
only re-enter matrix through ATP synthase
complex

b) ATP Synthase Complex

- ATP synthase complex / stalk particle  coupes
exergonic passage of H+ to endergonic
phosphorylation of ATP from ADP
- F0 stalk  membrane-spanning proton channel,
allows for proton movement
- F1 particle  attached to F0 stalk on matrix side of membrane,
catalyses ATP formation
- F1 barrel is turned as protons move through F0 stalk,
movement draws in ADP and inorganic phosphate, release
ATP

c) Chemiosmosis
- using kinetic egy of passing H+ down electrochemical grad, generate ATP from ADP
and Pi
- Amt of ATP produced depends on no. of H+ pumped into intermemb space as e- are
passed down ETC
- Dependent on no. of e- contributed by reduced coenz NADH and FADH2 
originated from glycolysis & Krebs cycle

For each 2 e- from NADH / Reduced For each 2 e- from FADH2 / Reduced
NAD and passed down to ETC FAD and passed down to ETC
10 H+ pumped across inner mito memb H+ pumped across inner mito memb into
into intermembrane space intermembrane space
Re-entry of H+ into matrix provides egy to Re-entry of H+ into matrix provides egy to
generate 3 ATP molq generate 2 ATP molq

6. Overall ATP Yield

Reaction Red NAD Red FAD ATP
Cytoplasmic reactions (glycolysis) +2 0 +2
Mitochondrial reactions (link reaction) +2 0 0
Krebs Cycle +8 +2 +2
Oxidative Posphorylation -10 0 34/32
Total 0 0 38/36

ANAEROBIC RESPIRATION

a) What it Is
- under anaerobic conditions, no further oxidation of pyruvate occurs, no acetyl CoA
formed, no additional ATP generated
- 2 ATP mol per glucose in glycolytic pathway  cells must consume glucose more
rapidly in order to maintain steady-state cellular ATP lvls
- oxygen independent process, occurring in cytosol
- uses organic molq as terminal e- acceptors, results in release of organic/inorganic by-
products
- NAD regenerated by transfer of e- from NADH to pyruvate, end pdt of glycolysis

b) 2 Types
Lactic Acid Fermentation Alcohol Fermentation
Equation NADH + C3H4O3 (pyruvate)  NADH + C3H4O3 (pyruvate) 
NAD + C3H6O3 (lactate) NAD + C2H5OH (ethanol) + CO2
Steps Involved Pyruvate reduced directly by NADH Pyruvate is converted to ethanol in
to form lactate as waste pdt 2 steps:
No release of CO2 1. CO2 released from pyruvate,
converted to acetaldehyde
2. acetaldehyde reduced by
NADH to ethanol
Occurrence Occurs in animals & certain fungi / Fungi : Yeast
bacteria Most plant tissues
Animals
- short term  satisfies greater
priority of regenerating NAD
 - long term  lactic acid is toxic,
must be removed
Certain fungi and bacteria:
- used in diary industry to make
cheese / yoghurt
Products Lactic Acid Ethanol
NAD NAD

COMPARING ENERGY YIELD

Aspect Aerobic Anaerobic

Alcoholic Lactic Acid
No. of ATP produced 38 2 2
per glucose
Total Energy released 2880 kJ 210 kJ 150 kJ
by complete ox of 1
glucose
Energy carried in ATP 30.6 kJ 61.2 kJ 61.2 kJ
Efficiency of Energy 40.4% 29.1% 40.8%
Transfer