Catabolism and Anabolism
Breakdown
Proteins to Amino Acids, Starch to Glucose
Synthesis
Amino Acids to Proteins, Glucose to Starch
Metabolism
is
the
sum
of
Catabolism
and
Anabolism
Opposite chemical processes. Catabolism releases energy (exergonic), and
Anabolism takes up energy (endergonic)
We can consider these bioenergetics in terms
of the physical laws of thermodynamics
Energy and Metabolism
Common
intermediate
As vias catabólicas convergem para uns poucos produtos finais
As vias anabólicas divergem para a síntese de muitas biomoléculas
Breakdown of macromolecules to
building blocks -- generally hydrolytic
Metabolic Pathways
• The enzymatic reactions of metabolism
form a network of interconnected
chemical reactions, or pathways.
• The molecules of the pathway are called
intermediates because the products of
one reaction become the substrates of
the next.
• Enzymes control the flow of energy
through a pathway.
Enzyme 1
A
Enzyme 2
Reaction 2
Starting
molecule
•
D
C
B
Reaction 1
Enzyme 3
Reaction 3
Product
A metabolic pathway has many steps
– That begin with a specific molecule and end with a product
– That are each catalyzed by a specific enzyme
Intermediary Metabolism
Mutienzyme complex
Separate
enzymes
Membrane
Bound System
Organization of Pathways
Linear
Closed Loop
(intermediates recycled)
Spiral
(same set of enzymes used
repeatedly)
Oxidation-Reduction Reactions
• Oxidation occurs via the loss of hydrogen or the gain
of oxygen
• Whenever one substance is oxidized, another
substance is reduced
• Oxidized substances lose energy
• Reduced substances gain energy
• Coenzymes act as hydrogen (or electron) acceptors
• Two important coenzymes are nicotinamide adenine
dinucleotide (NAD+) and flavin adenine dinucleotide
(FAD)
Comparação dos estados de
oxidação dos átomos de carbono
nas biomoléculas
(quanto mais oxidado mais estável
é a molécula, logo menos energia
pode ser extraída da quebra das
ligações)
Four general
stages in the
biochemical
energy production
process in the
human body.
ATP - Adenosine Triphosphate
ATP powers most energy
requiring process in living
systems.
Components
Energy stored in the triphosphate group
– Cells use ATP’s to drive endergonic reactions
– ATP
ADP (releases energy)
– Cells are continually producing new ATP’s
– ADP
ATP (requires energy)
ATP - the energy “currency” of cells
The three types of cellular work
– Are powered by the hydrolysis of ATP
P
i
P
Motor protein
Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
ATP
P
P
Solute
P
Solute transported
(b) Transport work: ATP phosphorylates transport proteins
P
Glu +
NH2
+
NH3
Reactants: Glutamic acid
and ammonia
P
i
Glu
Product (glutamine)
made
(c) Chemical work: ATP phosphorylates key reactants
i
i
Flavin Adenine Dinucleotide, FAD (a) and
Nicotinamide Adenine Dinucleotide, NAD (b)
Carbohydrate Metabolism
• Since all carbohydrates are transformed into glucose,
it is essentially glucose metabolism
• Oxidation of glucose is shown by the overall reaction:
C6H12O6 + 6O2  6H2O + 6CO2 + 36 ATP + heat
• Glucose is catabolized in three pathways
– Glycolysis
– Krebs cycle
– The electron transport chain and oxidative
phosphorylation
DG = -686kcal/mol of glucose
Carbohydrate Catabolism
transferring a phosphate
directly to ADP from
another molecule
use of ATP
synthase and
energy derived
from a proton
(H+) gradient to
make ATP
Glycolysis
• A three-phase pathway in which:
– Glucose is oxidized into pyruvic acid (PA)
• It loses 2 pairs of hydrogens
– NAD+ is reduced to NADH + H+
• It accepts 2 pairs of hydrogens lost by glucose
– ATP is synthesized by substrate-level phosphorylation
• Pyruvic acid: end-product of glycolysis
– Moves on to the Krebs cycle in an aerobic pathway (i.e.
sufficient oxygen available to cell)
– Is reduced to lactic acid in an anaerobic environment
(insufficient O2 available to cell)
– pyruvic acid
lactic acid
Glycolysis
Energy investement phase
Glycolysis: Phase 1 and 2
• Phase 1: Sugar activation
– Two ATP molecules activate glucose into
fructose-1,6-diphosphate
• The 1 and 6 indicate which carbon atom to which
they are attached.
• Phase 2: Sugar cleavage (splitting)
– Fructose-1,6-bisphosphate (6 C’s) is split into
two 3-carbon compounds:
• Glyceraldehyde 3-phosphate (GAP)
Glycolysis: Phase 3
• Phase 3: Oxidation and ATP formation
– The 3-carbon sugars are oxidized (reducing
NAD+); i.e., 2 H’s + NAD
NADH2
– Inorganic phosphate groups (Pi) are attached to
each oxidized fragment
– The terminal phosphates are cleaved and
captured by ADP to form four ATP molecules
– The final products are:
• Two pyruvic acid molecules
• Two NADH + H+ molecules (reduced NAD+)
• A net gain of two ATP molecules
ATP Production and Glycolysis
Glycolysis
•
First stage of glucose catabolism.
•
No oxygen needed.
• All organisms uses this process.
• It occurs in the cytoplasm where the necessary enzymes are located.
• 6C Glucose is converted into two 3C pyruvate.
• Small amount of energy, 2ATP, is produced.
Pathway of glycolysis is strictly regulated according to the cell’s needs
for energy.
The rate limiting step of the pathway is reaction 3, the phosphorylation
of F 6-P, which is catalyzed by phospho-fructokinase.
Anaerobic Metabolism
Fermentation in animal cells…
•
Lactic Acid Fermentation
•
Breakdown of glucose in absence of
oxygen
– Produces 2 molecules of lactic
acid and 2 molecules of ATP
Phases
– Glycolysis
– Lactic acid formation
Anaerobic Metabolism
Fermentation in plants, yeast…
Again…only 2
ATP per glucose
Ciclo de Cori
Gluconeogénese
Sintese de "glucose nova" a partir de metabolitos
comuns
•
•
•
•
Os seres humanos consumem 160 g de glucose por dia
75% dessa é consumida no cérebro
Os fluidos corporais contêm apenas 20 g de glucose
As reservas de glicogénio rendem 180-200 g de glucose
•
Portanto o corpo deve ser capaz de sintetizar a sua própria glucose
Gluconeogénese
•
Ocorre principalmente no figado e nos rins.
•
Não é uma mera reversão da glicólise por duas razões:
O balanço energético tem que mudar de modo a tornar a
gluconeogenese favorável (ΔG da glicolise = -74 kJ/mol)
A regulação de uma das vias deve ser activada e a da via reversa
deve ser inibida – isto requer algo de novo !
•
Sete dos passos da glicólise estão conservados e três passos são substituidos:
Passos 1, 3, e 10 (que são os passos regulados!)
•
As reacções novas devem seguir um novo caminho de reacção espontâneo (G
negativo na direcção da sintese de açucar), e devem ser regulados de maneira
diferente.
Aerobic Metabolism
Glycolysis = 2 ATP
Krebs Cycle and ETC = 34 ATP
If enough O2 is present…
To Krebs
Cycle and
ETC
~ 36 more ATP
per glucose!
Krebs Cycle: Preparatory Step
• Occurs in the mitochondrial matrix and is fueled by
pyruvic acid and fatty acids
• Pyruvic acid from glycolysis is converted to acetyl
coenzyme A (A-CoA) in three main steps:
– Decarboxylation
• 1 carbon is removed from pyruvic acid; 3C  2C molecule
• The lost carbon forms carbon dioxide; exhaled
– Oxidation
• 2 Hydrogen atoms are removed from pyruvic acid (‘oxidation’) and
picked up by NAD
• NAD+ is reduced to NADH + H+ (see next slide)
– Formation of acetyl CoA – the resulting acetic acid is combined with
coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA (ACoA)
Krebs Cycle
• An eight-step cycle in which each acetic acid is
decarboxylated and oxidized, generating:
– Three molecules of NADH + H+ (ox/red)
– One molecule of FADH2 (ox/red)
– Two molecules of CO2 (decarboxylation)
– One molecule of ATP (substrate level
phosphorylation
• For each molecule of glucose entering glycolysis, two
molecules of acetyl CoA enter the Krebs cycle
Krebs Cycle
Krebs Cycle
After glycolysis, pyruvate oxidation, and the
Krebs cycle, glucose has been oxidized to:
- 6 CO2
- 4 ATP
- 10 NADH
These electron carriers proceed
- 2 FADH2
to the electron transport chain.
Electron-Transport Chain
Electron Transport Chain
• Food (glucose) is oxidized and the released hydrogens:
– Are transported by coenzymes NADH and FADH2
– Enter a chain of proteins bound to metal atoms (cofactors)
– Combine with molecular oxygen to form water
– Release energy
• The energy released is harnessed to attach inorganic
phosphate groups (Pi) to ADP, making ATP by oxidative
phosphorylation
– “phosphorylation” - to add phosphate to a substance
» ADP + P
ATP
Mechanism of Oxidative Phosphorylation
• The hydrogens delivered to the chain are split into protons (H+)
and electrons
– The protons are pumped across the inner mitochondrial
membrane to the intermembrane space
– This creates a pH and concentration gradient (of H+)
– The electrons are shuttled from one acceptor to the next
• Electrons are delivered to oxygen, forming oxygen ions
• Oxygen ions attract H+ that were pumped into the
intermembrane space to form water
• H+ that were pumped to the intermembrane space:
– Diffuse down their gradients back to the matrix via ATP
synthase (from greater to lesser concentration)
– Release energy to make ATP
Proton Pumps: every two electrons passed through the ETC
produces 10 H+ ions from the mitochondrial matrix to the
intermembrane space.
NADH
FMN/Fe-S
Succinate/ FAD
Q
Cytb/Cytc1
Cytc
Cyta/Cyta3
O2
The Chemiosmotic Theory
Proposed by Peter Mitchell in the 1960’s (Nobel Prize 1978)
ATP is accompanied by the
flow of protons from the
intermembrane space back
into the mitochondrial
matrix. The proton flow
results from an
electrochemical gradient
across the inner
mitochondrial membrane.
H+ flow forms a circuit
(similar to an electrical circuit)
ATP Synthase
• The enzyme
consists of three
parts: a rotor, a
knob, and a rod
• Current created by
H+ causes the rotor
and rod to rotate
• This rotation
activates catalytic
sites in the knob
where ADP and Pi
are combined to
make ATP
http://vcell.ndsu.nodak.edu/animations/etc/movie.htm
Energy Yield of Respiration
theoretical energy yields
- 38 ATP per glucose for bacteria
- 36 ATP per glucose for eukaryotes
actual energy yield
- 30 ATP per glucose for eukaryotes
- reduced yield is due to “leaky” inner
membrane and use of the proton gradient for
purposes other than ATP synthesis