Cellular Metabolism Lecture Outline

• Energy Systems & Flow

• Metabolism Basics
• Cellular Respiration
– Glycolysis
– Citric Acid Cycle
– Electron Transport Chain & Oxidative
Phosphorylation
• Substitutes – what can be used besides
Part 4 - Cell Physiology glucose & how?

Energy Systems & Flow Energy Systems and Flow

• Energy is stored in two macro systems

– Plants & Animals
• Both flora and fauna are composed of additional subsystems
with both storage and flows
• Energy flows between these two storages when
consumption occurs
• Entropy increases at each level of consumption
(trophic level)
• We are concerned with chemical energy use and
conversion to ATP = cellular respiration
– C6H1206 + 6O2 = 6CO2 + 6H2O + 36ATP

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Lecture Outline Metabolism Basics
• Energy Systems & Flow • Metabolism:
– The sum of all chemical reactions that occur in the
• Metabolism Basics body
• Cellular Respiration – Require the use of enzymes and coenzymes

– Glycolysis • General Classification of chemical reactions

– Anabolic
– Citric Acid Cycle • Those that create larger molecules
– Ex. glycogenesis
– Electron Transport System & Oxidative
– Catabolic
Phosphorylation • Those that breakdown larger molecules into smaller
• Substitutes – what can be used besides molecules
– Ex. glycogenolysis
glucose & how?

Metabolism Basics Metabolism Basics

• Special types of metabolic reactions
1. Oxidation – Reduction • Special types of metabolic reactions
• A coupled reaction in which electrons are transferred from 2. dehydration-hydrolysis
one molecule to another
• This is a MAJOR player in the ATP production pathway • Uses hydrolase class of enzymes
• Mediated by oxioreductase class of enzymes • Removing water to create larger molecules
• Oxidation • Adding water to split larger molecules into
– Transfers electrons from a Glyceraldehyde 3-phosphate smaller molecules
molecule to oxygen (removes e-)
– Removes H+ P NAD+ 3. addition-subtraction-exchange
» A catabolic pathway • Transferases – mediate exchanges
• Reduction NADH
– The gain of electrons from a
• Lyases – mediate addition/removal
molecule
1,3-Bisphosphoglycerate
• The addition, removal or exchange of
» An anabolic pathway chemical groups between molecules
– Carboxylation – Decarboxylation
– Example: Glyceraldehyde 3-phosphate is oxidized (and
phosphorylated) to 1,3-Bisphosphoglycerate – Phosphorylation – dephosphorylation

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Metabolism Basics Lecture Outline
• Special types of metabolic reactions • Energy Systems & Flow
4. Ligation Reactions • Metabolism Basics
– Molecular groups are joined using energy • Cellular Respiration
– Uses ligase class of enzymes – Glycolysis
– Ex. Formation of acetyl CoA, succinyl CoA – Citric Acid Cycle
– Electron Transport System & Oxidative
Phosphorylation
• Substitutes – what can be used besides
glucose & how?

Production of ATP
Glycolysis
Overview hexokinase

Recall the overall equation: 1. Glucose upon entering the cell is

phosphorylated to Glucose 6-
C6H1206 + 6O2 = 6CO2 + 6H2O + 36ATP phosphate
– Additive reaction, enzyme is phosphoglucose
To accomplish this requires different processes at hexokinase, converting ATP to isomerase
different places within the cell ADP and adding P to 6th carbon
of glucose
Step 1 – Glycolysis
2. Glucose 6-phosphate is converted
- formation of two pyruvates to Fructose 6-phosphate by
Step 2 – Pyruvate oxidative decarboxylation phosphoglucose isomerase phosphofructokinase
- formation of two acetyl CoA 3. Additional phosphate group added
by phosphofructokinase to make
Step 3 – Citric Acid Cycle Fructose 1,6-bisphosphate
- end product (oxaloacetate) combines 4. Enzyme aldolase splits Fructose aldolase
with acetyl CoA to start, forming the 1,6-bisphosphate into two
same end product dihydroxyacetone phosphate
molecules
Step 4 – Electron Transport System
use of high energy protons and
5. Trios phosphate isomerase then
converts dihydroxyacetone to
electrons (from coenzymes) to power glyceraldehyde 3-phosphate trios phosphate
ATP synthesis isomerase

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Glycolysis glyceraldehyde
3-phosphate
dehydrogenase
Glycolysis
5. Glyceraldehyde 3-phosphate (G3P)
is oxidized (NAD+ is reduced to
NADH) and has phosphate added • Animation
to third carbon by glyceraldehyde
• End result:
phosphoglycerate
3-phosphate dehydrogenase to kinase
make 1,3-bisphosphoglycerate (1,3
BPG) – 2 ATP produced
6. ADP undergoes phosphorylation as
1,3 BPG is dephosphorylated by phosphoglycerate – 2 NADH produced
phosphoglycerate kinase, making mutase
3-phosphoglycerate molecules – 2 pyruvate molecules
7. 3-phosphoglycerate is converted to
2-phosphoglycerate by
phosphoglycerate mutase enolase

8. 2-phosphoglycerate is converted
by phosphoenol pyruvate by
enolase
9. phosphoenol pyruvate is pyruvate
dephosphorylated as ADP is kinase
phosphorylated to Pyruvate by
pyruvate kinase

Pyruvate Oxidative
Kreb’s Cycle
Decarboxylation (Link reaction)
• Goals of Krebs Cycle
• This is mediated by a large enzyme complex (pyruvate – Combine end product
dehydrogenase) that converts pyruvate to Acetyl CoA of last cycle with newly
• Occurs within the mitochondria formed acetyl CoA
• NAD+ is reduced to NADH, – Through a series of
• Carbon dioxide is released oxidation/reduction,
addition/subtraction,
– This leaves a 2 carbon group (acetyl) to which CoA is attached and ligand reactions
• Acetyl CoA is formed Why is this an important step? oxidize pyruvate to
• Animation carbon dioxide and water AND
• Make an end product (oxaloacetate) that can start the cycle
Pyruvate again
dehydrogenase
O O Complex
O
⎜⎜
• Produce GTP (which phosphorylates ADP to ATP)
⎜⎜ ⎜⎜
H3C – C – C – O- H3C – C – S – CoA + CO2 • Reduce NAD+ and FAD coenzymes which are to be used in
pyruvate
the Electron Transport System
NAD+ NADH
acetyl CoA

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 Kreb’s Cycle Kreb’s Cycle
5. Succinyl CoA is
Steps converted into
citrate synthase citrate synthase
1.Acetyl CoA combines Succinate as CoA is
with oxaloacetate to aconitase subtracted and GDP is aconitase
form Citrate using phosphorylated by malate dehydrogenase
citrate synthase succinyl CoA
synthetase
2.Citrate is converted 6. Succinate is oxidized
to Isocitrate by isocitrate dehydrogenase to Fumarate by isocitrate dehydrogenase
aconitase succinate
3.Isocitrate is oxidized dehydrogenase,
and decarboxylated reducing FAD in the
by isocitrate process fumarase
dehydrogenase to 7. Fumarate is converted
form α-ketoglutarate α-ketoglutarate dehydrogenase to Malate by α-ketoglutarate dehydrogenase
fumarase, adding
4.α-ketoglutarate is water in the process
converted into 8. Malate is converted
succinyl CoA by α- back to oxaloacetate succinate dehydrogenase
ketoglutarate by malate
dehydrogenase dehydrogenase and is
further oxidized, and
NAD+ is reduced. succinyl CoA synthetase

Kreb’s Cycle Electron Transport System

• Goal of Electron Transport System
• Animation – Utilize the protons and
electrons that the
• From Kreb’s Cycle: coenzymes (NAD+ and FAD)
“picked up” during glycolysis
– Each of the NADH (NADH+H+) is capable of (NAD+ only) and Kreb's cycle
providing the energy to synthesize 2.5 ATP molecules (both NAD+ and FAD).
– The electrons “power” the
– Each of the FADH2 coenzymes is capable of movement of H+ (protons)
synthesizing 1.5 ATP molecules across the inner membrane
space creating a proton motive
• These energized coenzymes are utilized by mitochondrial gradient
membrane components in the electron transport system – This gradient is utilized along
with oxygen that has entered
– GTP quickly phosphorylates ADP to ATP the mitochondrial matrix to power a rotary ATP synthase
transmembrane protein complex
– The “spent” electrons are picked up by oxygen
• Oxygen is the final electron acceptor in the process of aerobic
cellular respiration – it’s why we breathe.

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Electron Transport System Electron Transport System

1. Membrane complex I enzymatically (NADH dehydrogenase) 3. Cytochrome c (Cyt c) then transfers them to
removes the high energy electrons from NADH (oxidizing it) and
pumps protons into the intermembrane space. membrane complex IV, which pumps additional
- The electrons are picked up by membrane carrier ubiquinone (UQ) protons to the intermembrane space.
2. Ubiquinone transfers them to membrane complex III which uses the - The “spent” electrons (along with H+ that return to the matrix)
energy to pump additional protons into the intermembrane space. are transferred to their final electron acceptor = oxygen!

Oxidative Phosphorylation Oxidative Phosphorylation

• The continuation of the electron • Animation
transport system
– Utilizes the protons potential energy
that is stored in the intermembrane
space
• A gradient has been established…
– High proton concentration in the
intermembrane space, low proton
concentration in the matrix
– The only way (besides leaking and or
binding with oxygen too early to form
free radicals) through the membrane and
therefore down the gradient is by the
large ATP synthase complex.
– 3 hydrogen ions power the ATP synthase,
which use the energy to reattach
Phosphate to ADP making ATP

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End Result of Aerobic Cellular
Lecture Outline
Respiration
• ATP numbers… • Energy Systems & Flow
• 8 NADH = 20 ATP • Metabolism Basics
• 2 NADH = 3 ATP • Production of ATP
• 2 FADH = 3 ATP – Glycolysis
• Glyc/Kreb 4 ATP – Citric Acid Cycle
– Electron Transport System & Oxidative
30 ATP Phosphorylation
• Substitutes – what can be used besides
glucose & how?

Substitutes Substitutes
• Triglycerides • Proteins can be
can be utilized utilized:
– Formation of new
glucose from non
glucose sources such
as amino acids
(gluconeogenesis)
– Carbon backbones of
amino acids can be
converted into acetyl
CoA

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Wrap Up
• Eating and breathing provide all the key
elements for cellular respiration
– Metabolic pathways and membrane
components take care of the rest of ATP
production
– Without ATP
• No communication, no movement – anywhere!