Transcript Chapter 13 - Cell Metabolism

Chapter 13
How Cells Obtain
Energy from Food
From Chapter 3 (Energy)
• Sun is source of all energy
• Through photosynthesis/dark reactions, plants convert
solar energy  chemical energy + sugars
• Other organisms consume sugars, convert sugars to
chemical energy
– Chemical bond energy in food
– Catabolism of sugars (glucose) is most direct pathway
to chemical energy
Sugar  Chemical Energy
• Use steps to harvest all the energy and not waste it as heat
• Aerobic metabolism yields the most energy (O2 needed)
• Metabolites more oxidized than glucose
– Enzymes catalyze reactions
• Oxidation reactions must be coupled with reduction reactions
– The reduced molecules are the carriers (NADH and NADPH)
Sugar  Chemical Energy
• Overall products of sugar catabolism:
– CO2
– H2O
– Reduced (activated) carriers
• NADH
• NADPH
– In mitochondria, reduced carriers now oxidized
(lose electrons)
– Electrons released to electron transport system
» Allow ATP synthesis in mitochondria
Stage 1 - Digestion
In eukaryotes (mammals):
• Digestion
– HCl -- stomach
– Enzymes – mouth, stomach, small intestine
– Enzymes in the lysosome for internal cellular digestion
• Absorption through specialized cells in small intestine
 bloodstream  body’s cells
• Metabolism begins in cell cytosol
Location of
Macromolecules
in Cell
Stage 2 - Glycolysis
• Glycolysis starts in the cytoplasm
• Glucose (6C)  2 pyruvate (3C each)
– Other sugars can be used but must convert to
intermediates of glycolysis
• 2 carrier molecules generated per pyruvate
– 2 molecules ATP (carries energy)
– 2 reduced NADH (carries electrons)
• Pyruvate molecules move to the mitochondria
Stage 3 – Kreb’s Cycle/ETC
• In the mitochondria pyruvate broken down to CO2 and the
remaining 2 Cs (acetyl group) are added to Coenzyme A
– Also can get Acetyl CoA from fats
• Each acetyl CoA transfers the 2C’s to citric acid cycle
where carrier molecules are generated
– GTP carries energy
– NADH/FADH2 carry electrons
• Electrons  electron transport chain
– Release energy used for oxidative phosphorylation
– O2 needed for successful reaction ADP + Pi  ATP
– ATP moved to the cytosol for use
Glycolysis
• 10 reactions, each catalyzed by an enzyme
• Products or intermediates become more oxidized
through pathway
– Doesn’t react with oxygen atoms; rather lose electrons to
carriers
• 2 NADH generated from catabolism 1 glucose
• Some steps are not spontaneous (+DG)
– Coupled with subsequent spontaneous reactions
Glycolysis
• Uses 2 ATP to catabolize glucose
– In coupled reactions – hydrolysis of ATP allows nonspontaneous reactions to proceed
– Phosphates from ATP added to intermediates
• Form high energy phosphate bonds
• Now intermediates have higher energy
• In later steps, generates 4 ATP
– When phosphates cleaved from intermediates
• Overall glycolysis yields (net gain) 2 ATP
Overall Process
Glycolysis
Glycolysis
Glycolysis
Glycolysis
Glycolysis
Net Result of Glycolysis
• Glucose + 2 ATP  2 NADH + 4 ATP + 2 pyruvate
• Net energy outcome 2 NADH and 2 ATP
What to Know About Glycolysis
• 10 enzymes / 5 reaction types
– Kinases – add a phosphate group to intermediates,
phosphate transfer
– Isomerases – rearranges the atoms in the intermediates
– Dehydrogenase – causes a redox reaction, electron ends
up on FADH2 or NADH
– Dehydrations – removal of H2O
– Cleavage reaction – split glucose to 2 3-C molecules
• Net outcome of glycolysis
Steps and Reactions
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Step 1 – kinase, phosphate transfer
Step 2 – isomerase, rearrange atoms
Step 3 – kinase, phosphate transfer
Step 4 – cleavage to 2 3-C molecules
Step 5 – isomerase, rearrange atoms
Step 6 – dehydrogenase, make NADH
Step 7 – kinase, phosphate transfer
Step 8 – isomerase, rearrange atoms
Step 9 – removal of H2O
Step 10 – kinase, phosphate transfer
Enzymatic Coupling
• Steps 6 and 7 are coupled to take advantage of the highenergy phosphate intermediate to create ATP
• Step 6: glyceraldehyde 3-phosphate has a inorganic
phosphate group added to create 3-phosphoglycerate,
substrate for Step 7 and generates NADH
• Step 7: 1,3-bisphosphoglycerate releases the energy in
the phosphate bond to create 1 ATP for each 1,3bisphosphoglycerate
Overall Results
• Enzyme-mediated energy storage through coupled reactions to
create high energy bonds
• Intermediate is higher in energy than before
– Has second high energy phosphate bond
– NADH is generated and will also increase energy when it
participates in oxidative phosphorylation
High Energy Bonds
Fermentation
• Can generate ATP in
absence of O2 – anaerobic
• Anaerobic organisms create
ATP through glycolysis
– Pyruvate converted to
ethanol and CO2 (yeast) or
lactate (muscle)
• Process called fermentation
Stage 3
• Pyruvate is moved to the mitochondria
• In the presence of O2 it is converted to 1 molecule of CO2 and
the remaining 2 C’s are attached to Coenzyme A, creating
Acetyl CoA using pyruvate dehydrogenase complex
• Also generates a molecule of NADH
Fatty Acids as Energy Source
• Fatty acids can be linked to
CoA (fatty acyl CoA) and
therefore yield acetyl CoA
that can enter the citric acid
cycle
• Generates NADH and
FADH2 for each acetylCoA
• Amino acids also can be
made to acetylCoA and
used in the Kreb’s cycle
Energy Produced in Mitochondria
• Fats and sugars are major sources of energy
• Acetyl CoA is made in the mitochondria
• No surprise to learn that the energy is also harvested
in the mitochondria
• In bacteria – glycolysis and citric acid cycle in cytosol
Citric Acid Cycle
• 2/3 of oxidation of C compounds in the average cell
• End product is CO2 (waste) and NADH high energy
molecules (used later)
• Requires O2 to regenerate NAD+ but not actually used in
reactions
• Link the acetyl group of Acetyl CoA to 4 C molecule,
oxaloacetate, to make 6 C citrate
• By end of cycle, all the C of glucose is released as CO2,
remembering that 1 CO2 was released in previous stage
Citric Acid Cycle
(TCA Cycle, Kreb’s Cycle)
***
Activated Carriers
Two new energy molecules are introduced
– FADH2 (flavin adenine dinucleotide)
• High energy electrons and H
– GTP (ribonucleotide)
• Similar to ATP and will give up PO4 to ADP to make ATP
• Requires O2 but as H2O (red circle)
• Some of the steps products can leave mitochondria and used in the
cytosol to make precursors like amino acids
Steps and Reactions
• Step 1 – add acetyl CoA to oxaloacetate, citrate (6 C)
• Step 2 – isomerase, rearrange atoms (6 C)
• Step 3 – dehydrogenase, make NADH, lose CO2 (5 C)
• Step 4 – dehydrogenase, make NADH, lose CO2, add CoA
back to molecule (4 C)
• Step 5 – generate GTP, remove CoA (4 C)
• Step 6 – dehydrogenase, make FADH2, rearrange atoms (4 C)
• Step 7 – add H2O (4 C)
• Step 8 – dehydrogenase, make NADH, regenerates
oxaloacetate (4 C), why a cycle
Electron-Transport Chain
• Final step in energy generation –
most energy released here
• e- of NADH and FADH2 move through
the chain, moving to lower energy
level
• Occurs in the inner membrane of the
mitochondria
• Specialized molecules accept and
donate e- as they move down chain
• Create an electrochemical gradient
– As e- move down chain, H+ move across
the membrane, altering the concentration
of H+ on either side = gradient
– Gradient used to generate ATP (Chapter
14)
Oxidative Phosphorylation
• e- eventually end up on O2 and with the H+ form H2O – e- is at
least energy level
• Complete oxidation of glucose produces 6 CO2, H2O and ~30
ATP
• Glycolysis alone produces just 2 ATP
• In bacteria – plasma membrane
• In eukaryotes – in the inner mitochondrial membrane
Storing and Using Food
• Need to generate ATP constantly, can because store “food”
within our cells
• Fatty acids in fat cells, globules in cells
– Holds more energy gram for gram than sugar
• Glucose stored as glycogen, a branched polysaccharide in
granules in animal cell cytoplasm
– Used when not enough glucose in bloodstream
– Released as glucose 1-phosphate and can enter
glycolysis
Sugar Storage in Plants and Mammals
Plants
• Have chloroplasts as well as mitochondria
– Mitochondria will generate ATP from the sugars made
during photosynthesis
• Especially in cells without chloroplasts such as roots or
when without sunlight
• Excess sugars can be converted to fats or starch, the
equivalent to glycogen in animals, different branching
pattern
– Stored in the chloroplast
Chloroplasts and Mitochondria
• Chloroplasts make ATP and NADPH that cannot leave
• ATP and NADPH converted to sugar that can leave and be
used in glycolysis and ATP generation in the mitochondria
and into other building blocks
Biosynthetic Pathways Begin with Glycolysis or TCA Cycle
• Intermediates can be
used by other
enzymes as the
starting point in
making amino acids,
nucleotides, lipids
and other small
organic compounds
• Black arrows – one
enzyme reaction
• Red arrows – multi
step reactions
Pathway Interactions
• Some molecule can be
substrate in many
different pathways
• Elaborate network of
control mechanisms
Bringing It All Together
Metabolism
High ATP Levels
Low ATP Levels
Anabolism
Catabolism
Glycogen
Fats
Proteins
Glycogen
Fats
Proteins