Cellular respiration

Introduction to cellular respiration

• adenosine triphosphate(ATP)

• substrate-level phosphorylation
• oxidative phosphorylation
• cellular respiration

• Electron carriers(shuttles): small organic molecules which pick up electrons from one molecule and drop them off with another
• 2 types of electron carriers in cellular respiration: NAD+(nicotinamide adenine dinucleotide)/ FAD(flavin adenine dinucleotide)
• Redox reactions(oxidation-deduction reactions): reactions involving electron transfers

1. one molecule loses electrons: oxidized(OIL)
2. one molecule gains electrons: reduced(RIG)

• in the context of biology: 

1. if a carbon-containing molecule gains H or loses O, it's likely been reduced(gained electrons or electron density)
2. if a carbon-containing molecule loses H or gains O, it's likely been oxidized(lost electrons or electron density)

• The atoms that H is usually bound to(C, O, N, P)are more electronegative than H
• so, if a H and its electron join a molecule, the rest is going to hog the electron(become reduced)
• O is more electronegative than any of the other major atoms
• if it joins a molecule, it's likely going to pull away electron density(oxidize)
• electrons are at a higher energy level when they're with less electronegative atoms(C or H)
• electrons are at a lower energy level when they're with more electronegative atoms(O)
• in a breakdown of glucose, electrons are moving from higher energy level to lower(energy is releasing and captured!)

Steps of cellular respiration

• Glycolysis: glucose converted into 2 pyruvates, ATP made, NAD+ is converted to NADH
• *glycolysis without oxygen=fermentation. other 3 stages require oxygen to occur
• Pyruvate oxidation: pyruvate converted into acetyl CoA, CO2 released, NADH generated
• Citric acid cycle: end product of the cycle+acetyl CoA=initial product of the cycle. ATP, NADH, FADH2 produced, CO2 released
• Oxidative phosphorylation: electrons move down the chain, energy released, to pump protons out of matrix, forming a gradient, protons flow back into the matrix through an ATP synthase, making ATP

Glycolysis

Highlights of glycolysis

• takes place in the cytosol of a cell
• catalyzed by enzyme, phosphofructokinase
• energy requiring phase

1. glucose molecule rearranged
2. two phosphate groups(spend 2 ATP) are attached to it
3. make the modified sugar: fructose-1,6-bisphosphate
4. break into: glyceraldehyde-3-phosphate and DHAP(soon converted to the former one)

• energy releasing phase

1. glyceraldehyde-3-phosphate converted into pyruvate*2=2 pyruvates
2. 2 ATP and 1 NADH made *take place twice=4 ATP and 2 NADH

Detailed steps: Energy requiring phase

1. a phosphate group is transferred from ATP to glucose, making glucose-6-phosphate
2. glucose-6-phosphate is converted into fructose-6-phosphate
3. a phosphate group is transferred from ATP to fructose-6-phosphate, making fructose-1,6-bisphosphate *phosphofructokinase*
4. fructose-1,6-bisphosphate splits into glyceraldehyde-3-phosphate and DHAP
5. DHAP is converted into glyceraldehyde-3-phosphate

Detailed steps: Energy releasing phase

1. glyceraldehyde-3-phosphate lose 2 electrons and 2 protons, reducing NAD⁺->NADH and H⁺ *release energy* forming 1,3-biphosphoglycerate
2. 1,3-biphosphoglycerate donate a phosphate group to ADP(making ATP), turning into 3-phosphoglycerate
3. 3-phosphoglycerate is converted into 2-phosphoglycerate
4. 2-phosphoglycerate loses 1 molecule of water, becoming phosphoenolpyruvate(PEP)
5. PEP(unstable) donates a phosphate group to ADP(making ATP), turning into pyruvate

What happens to NADH

• if there's no NAD⁺ , glycolysis come to a halt
• when oxygen is present: through the electron transport chain, regenerating NAD⁺
• when oxygen is absent: NADH donates electrons to an acceptor molecule, regenerating NAD⁺

Pyruvate oxidation

Overview of pyruvate oxidation

• in eukaryotes, it takes place in the mitochondrial matrix
• in prokaryotes, it happens in the cytoplasm
• (glucose->)2 pyruvate converted into 2 acetyl CoA, producing 2 NADH and 2 CO2
• acetyl CoA acts as fuel for the citric acid cycle

Pyruvate oxidation steps

1. a carboxyl group is removed, released as a CO2
2. via step1, an acetyl group is oxidized, lose electrons, NAD⁺->NADH
3. an acetyl group is attached to Coenzyme A(CoA) to form acetyl CoA

The citric acid cycle

Overview of the citric acid cycle

• in eukaryotes, it takes place in the mitochondrial matrix
• in prokaryotes, it happens in the cytoplasm
• a closed loop, 8 major steps
• one turn of the citric acid cycle=2 CO2, 3 NADH, 1 FADH2, 1 ATP or 1 GTP
• the cycle goes around twice/glucose

Steps of the citric acid cycle

1. acetyl CoA+oxaloacetate=CoA group+citrate
2. citrate->isocitrate
3. isocitrate is oxidized->a-ketoglutarate+releasing 1 CO2, NAD+->NADH *isocitrate dehydrogenase
4. a-ketoglutarate is oxidized->succinyl CoA+releasing 1 CO2, NAD+->NADH *a-ketoglutarate dehydrogenase
5. succinyl CoA->succinate, ADP/GDP is forming ATP/GTP
6. succinate is oxidized->fumarate, FAD->FADH2
7. fumarate+water->malate
8. malate is oxidized->oxaloacetate, NAD+->NADH

Oxidative phosphorylation

Overview: oxidative phosphorylation

• found in the inner membrane of the mitochondria
• electron transport chain+chemiosmosis=oxidative phosphorylation
• delivery of electrons by NADH and FADH2
• electron transfer and proton pumping
• splitting of oxygen to form water
• gradient-driven synthesis of ATP

The electron transport chain

• a collection of membrane-embedded proteins and organic molecules
• in eukaryotes, it is found in the inner mitochondrial membrane
• in prokaryotes, it is found in the plasma membrane
• electrons go from a higher(less electron hungry) to a lower(more electron hungry) energy level
• regenerates electron carriers(NADH, FADH2)
• makes a proton gradient

1. NADH is very good at donating electrons, it can transfer its electrons directly to complex I
2. FADH2 is less good at donating electrons, it feeds electrons into the chain through complex II(doesn't pump H+) 
3. complex II: electron carrier 'ubiquinone(Q)', delivering electrons to complex III
4. complex III: another carrier 'cytochrome C(cyt C)', delivering electrons to complex IV
5. complex IV: passes the electrons to O2

Chemiosmosis

• proton gradient=electrochemical gradient=proton-motive force
• ATP synthase: adding phosphate to ADP, capturing energy(from the H+ gradient) as ATP
• energy stored in the proton gradient but not used to synthesize ATP->HEAT

Variations on cellular respiration

Fermentation and anaerobic respiration

• when no oxygen as an acceptor at the end of the electron transport chain
• fermentation pathways(glycolysis+extra reactions) come to join
• extra reactions: make alcohol(yeast), lactic acid(muscle)
• anaerobic cellular respiration: some bacteria or archaea use sulfate as an acceptor

Fermentation

• glycolysis+extra reactions
• the pyruvate made in glycolysis->NO oxidation, NO citric acid cycle->NO electron transport chain run 
• NADH made in glycolysis cannot turn back into NAD+
• extra reactions: is to regenerate NAD+

Alcohol fermentation

• NADH donates its electrons to a derivative of pyruvate, producing ethanol
• a carboxyl group is removed from pyruvate, releasing CO2, producing acetaldehyde
• NADH passes electrons to acetaldehyde, regenerating NAD+, forming ethanol

Lactic acid fermentation

• NADH transfers electrons directly to pyruvate, generating lactate(deprotonated form of lactic acid)
• bacteria that make yogurt
• muscle cells that have too little oxygen(when exercising very hard)

Facultative and obligate anaerobes

• facultative anaerobes: can switch between aerobic/anaerobic pathways(=fermentation)
• obligate anaerobes: can live only in the absence of oxygen