Carbohydrate Metabolism: Glycolysis, Citric Acid Cycle, Oxidative Phosphorylation

stages of cellular respiration

stage 1: acetyl-coA production (glycolysis)

stage 2: acetyle-coA oxidation (citric acid cycle)

stage 3: electron transfer and oxidative phosphorylation

fates of glucose

1: stored as glycogen

2: oxidized to pyruvate (via glycolysis)

3: oxidized to pentoses (via the pentose phosphate pathway)

what are the two phases of glycolysis?

preparatory phase and payoff phase

phosphorylation of glucose and its conversion to G3P

preparatory phase

oxidative conversion of G3P to pyruvate and the coupled formation of ATP and NADH

payoff phase

what is the end goal of the prep. phase of glycolysis?

cleavage of a 6 carbon compound into 2 triose phosphates (3 carbon molecules)

how many ATP are invested in the prep phase of glycolysis?

2 ATP

what is the order of products in the prep. phase of glycolysis?

1: glucose --> glucose 6 phosphate usin ATP & hexokinase

2: glucose 6 phosphate <--> fructose 6 phosphate using phosphokinase

3: fructose 6 phosphate --> fructose 1,6 bisphosphate using ATP & phosphofructokinase 1

4: fructose 1,6 bisphosphate <--> G3P & DHAP (glyceraldehyde 3-phsophate & dihydroxyacetone phosphate) using aldolase

priming phase of glycolysis prep. phase?

input of 2 ATP to convert glucose to fructose 1,6-bisphosphate

splitting stage of glycolysis prep. phase?

splitsing fructose 1,6-bisphosphate into 2 molecules of G3P

which steps of the prep. phase of glycolysis require ATP?

conversion of glucose to glucose 6-phosphate

conversion of fructose 6-phosphate to fructose 1,6-bisphosphate

what is the end goal of the payoff phase?

convert 2 G3P molecules into 2 pyruvate

what is the order of products in the payoff phase of glycolysis?

5: G3P & DHAP <--> (2) G3P (glyceraldehyde 3 phosphate) using triose phosphate isomerase

6: G3P <--> (2) 1,3 bisphosphoglycerate using G3P dehydrogenase

7: 1,3 bisphosphoglycerate --> (2) 3-phophoglycerate & 2 ATP using phosphoglycerate kinase

8: 3-phophoglycerate <--> (2) 2-phophoglycerate using phosphoglycerate mutase

9: 2-phophoglycerate <--> (2) phosphopenol pyruvate using enolase

10: phosphopenol pyruvate --> (2) pyruvate & 2 ATP using pyruvate kinase

how many ATP and NADH total are generated from the oxidation of G3P in the payoff phase

4 ATP and 2 NADH

what steps of the payoff phase of glycolysis yield ATP?

conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate

conversion of phosphoenol pyruvate to pyruvate

what steps of the payoff phase of glycolysis yield NADH?

conversion of G3P to 1,3-bisphosphoglycerate with the use of NAD+

Since the cytosol of cells has only a limited amount of NAD+, it is imperative for continuous glycolytic activity that the NADH be converted back (turned over) to NAD+. Without turnover of NADH, glycolysis will ...

stop for want of NAD+

how is NADH converted back to NAD+?

lactate dehydrogenase

the G3P dehydrogenase-phosphoglycerate kinase system is an example of

substrate level phosphroylation

pyruvate accomplishes ...

substrate level phosphorylation

what are the regulatory enzymes of the glycolytic pathway?

hexokinase, 6-phosphofructo-1-kinase, pyruvate kinase

what is the most important regulatory site in the glycolytic pathway?

6-phosphofructo-1-kinase as it is the rate limiting enzyme

what are the most important negative allosteric effectors in the glycolytic pathway?

citrate, ATP, and hydrogen ions

what are the most important positive allosteric effectors in the glycolytic pathway?

AMP, fructose 2,6-bisphosphatem Pi

negative and positive allosteric effectors of 6-phosphofructo-1-kinase signal different rates of glycolysis in response to changes in what?

energy state of the cell, internal environment of the cell, availability of alternate fuels, insulin/glucagon ratio

where does glycolysis occur?

cytosol

all 10 glycolytic enzymes are located where?

cytosol

T/F: Glycolysis is tightly regulated in coordination with other energy-yieldingpathways

true

in the payoff phase of glycolysis, the energy yielded from the oxidation of 2 G3P molecules is conserved in the formation of what?

NADH and ATP

What are the metabolic fates of NADH, and pyruvate produced in glycolysis?

NADH: electrons of NADH are shuttled to the mitochondrial electron transport chain

pyruvate (aerobic): under aerobic conditions pyruvate is converted to acetyl-CoA and then enters TCA cycle

pyruvate (anaerobic): under anerobic conditions pyruvate undergoes fermentation to become lactate (animals) or ethanol + CO2 (yeast)

where must pyruvate enter to participate in the TCA cycle?

mitochondria

different names of the TCA cycle

TCA cycle, citric acid cycle, Krebs cycle

oxidative decarboxylation of pyruvate is catalyzed by what complex ? how many enzymes is the complex composed of? how many coenzymes are required?

pyruvate dehydrogenase complex; 3 enzymes; 5 coenzymes

what are the steps of the TCA cycle?

1: aceytl-CoA to citrate

2: citrate to isocitrate

3: isocitrate to alpha-ketoglutarate + CO2 + NADH

4: alpha-ketoglutarate to succinyl-CoA + CO2 + NADH

5: succinyl-CoA to succinate + GTP

6: succinate to fumarate + FADH2

7: fumarate to malate

8: malate to oxaloacetate + NADH

9: oxaloacetate to acetyl-CoA

which steps in the TCA cycle produce CO2?

step 3: (isocitrate dehydrogenase) isocitrate to alpha-ketoglutarate

step 4: (alpha-ketoglutarate dehydrogenase) alpha-ketoglutarate to succinyl-CoA

what are the 3 key sites of regulation in the TCA cycle?

citrate sythase - ATP, NADH, & succinyl-CoA inhbit

isocitrate dehydrogenase - ATP inhibits, ADP & NAD+ activate

alpha-ketoglutarate dehydrogenase - NADH & succinyl-CoA inhibit, AMP activates

for every acetyl-CoA oxidized, the energy gain consists of what?

3 NADH, 1 FADH2, 1 GTP, 2 CO2

the overall rate of the TCA cycle is controlled by what?

rate of conversion of pyruvate to acetyl-CoA, and the regulatory sites/enzymes

Where in the cell do electron transport and oxidative phosphorylation occur?

inner mitochondrial membrane

what is the source of electrons for the electron transport chain? what do they generate?

NADH and FADH2 from the TCA cycle; generate a proton gradient across the inner mitochondrial membrane

in oxidative phosphorylation the proton gradient runs ... to drive ...

downhill, synthesis of ATP

what are reduction potentials and how do they account for free energy changes in redox reactions?

a species' tendency to gain electrons, with more positive values indicating a greater likelihood of reduction

What is the end goal of electron transport?

drive the generation of a proton gradient across the inner mitochondrial membrane

what are the four single-electron carriers

Heme C and Heme A in their respective cytochromes, Iron Protoporphyrin IX, Iron Sulfur Centers

How many electrons can ubiquinone carry?

2 electrons

What is the largest complex in electron transport?

complex I

Which electron transfer complexes can pump protons across the inner mitochondrial membrane?

Complex I, III, IV

in complex I, what is the ratio of H+ to e-?

4 H+ out per 2 e-

Complex I transfers electrons from _______ to _______

NADH to coenzyme Q/unbiquinone

Complex II transfers electrons from ________ to _________

FADH2 to coenzyme Q/ubiquinone

Complex III transfers electrons from __________ to _____________

coenzyme Q/ubiquinone to cytochrome c

Complex IV transfers electrons from ____________ to _______________

cytochrome C to oxygen

What is the terminal acceptor of the electrons in electron transport?

oxygen

UQH2 is a lipid or water soluble electron carrier of complex III?

lipid soluble

cyt c is a lipid or water soluble electron carrier of complex III?

water soluble

T/F: NADH cannot cross the inner mitochondrial membrane.

True

which complex in the electron transport chain transports H+ across the inner mitochondrial barrier?

complex IV

What are the two shuttle systems that will effect electron movement without NADH entering the mitochondria?

the Glycerophosphate shuttle and the Malate-aspartate shuttle

The glycerophosphate shuttle will result in _______ ATP per glucose, while the Malate-aspartate shuttle will result in ______ ATP per glucose.

30, 32

disrupt the tight coupling between electron transport and oxidative phosphorylation by dissipating the proton gradient

uncouplers

Two parts of ATP synthase

F0 and F1

Which part of ATP synthase is found embedded in the membrane?

F0

forms the transmembrane pore or channel through which protons move to drive ATP synthesis

F0

Which subunit of ATP synthase will rotate due to proton diffusion?

C

Which subunit of ATP synthase will rotate due to rotation of subunit C?

y

Which subunits are rotated by subunit y to make ATP?

a and B

In order to make 1 ATP, you need the movement of _______ protons across the membrane.

3