Unit 1 - Carbohydrates: metabolic pathways

first step in carb metabolism

glycolysis

purpose of glycolysis

oxidation/breakdown of glucose for energy production

where does glycolysis take place

cytosol

types of glycolysis

aerobic and anaerobic

anaerobic glycolysis

without oxygen

glucose → 2 pyruvate → 2 lactate

aerobic glycolysis

with oxygen

glucose → 2 pyruvate → 2 acetyl CoA

which step is different between aerobic and anaerobic glycolysis

last step

pyruvate → acetyl Co A (aerobic) or lactate (anaerobic)

first step of glycolysis

glucose phosphorylated by either glucokinase (liver) or hexokinase (muscle) into glucose 6 phosphate using 1 ATP molecule

1st rate limiting enzyme of glycolysis

gluockinase (liver) / hexokinase (muscle)

glucokinase activator (2nd pass only)

insulin

hexokinase inhibitor

glucose 6 phosphate

second step of glycolysis

glucose 6 phosphate turned into fructose 6 phosphate by isomerase

3rd step of glycolysis

fructose 6 phosphate turned into fructose 1,6 bisphosphate by phosphofructokinase (PFK)

2nd rate limiting enzyme of glycolysis

phosphofructokinase (PFK)

PFK inhibitor

cellular ATP (ATP produced from Krebs and ETC)

galactose in glycolysis

can also be turned into G6P using 1 ATP molecule

energy production differences when eating glucose vs galactose

same amount

kinases

transfer phosphate from an ATP molecule or vice versa

fructose in glycolysis

can be converted to fructose 6 phosphate using 1 ATP or directly converted to fructose 1,6 bisphosphate using 1 ATP

consequences of fructose skipping a step in glycolysis

skips 1 OR BOTH RATE LIMITING steps (hexo or gluco kinase always unnecessary for fructose) (PFK unnecessary for fructose → F1,6BP conversion) so it has a more direct route to fat production

4th step of glycolysis

fructose 1,6 bisphosphate splits into 1 dihydroxyacetone (DHAP) and 1 glyceraldehyde 3 phosphate by aldolase

5th step of glycolysis

DHAP converted into glyceraldehyde 3 phosphate by isomerase resulting in 2 G3P molecules

6th step of glycolysis

2 molecules of glyeraldehyde 3 phosphate converted into 2 molecules of 1,3 bisphospoglycerate by 2 glyeraldehyde 3 phosphate dehydrogenase enzymes

also converts 2 NAD molecules to NADH in this process

7th step of glycolysis

2 molecules of 1,3 bisphosphoglycerate converted into 2 molecules of 3 phosphoglycerate by 2 phosphoclycerate kinase enzymes

also forms 2 ATP molecules

8th step of glycolysis

2 molecules of 3 phosphoglcyerate converted to 2 molecules of 2 phosphoglycerate by 2 phosphoglycerate mutase enzymes

9th step of glycolysis

2 molecules of 2 phosphoglycerate converted to 2 molecules of phosphoenoyl pyruvate (PEP) by 2 enolase enzymes

10th step of glycolysis

2 molecules of phosphoenoyl pyruvate (PEP) converted to 2 molecules of pyruvate by 2 pyruvate kinase enzymes producing 2 ATP molecules

11th step of glycolysis in anaerobic conditions

2 molecules of pyruvate converted to 2 molecules of lactate by 2 lactate dehydrogenase enzymes

also uses 2 NADH → 2 NAD

11th step of glycolysis in aerobic conditions

2 molecules of pyruvate enter the mitochondrial membrane and are converted to 2 molecules of acetylene CoA by 2 pyruvate dehydrogenase enzymes

also forms 2 NADH molecules (2NAD→2NADH)

acetyl CoA molecules go where after glycolysis

to be combined with oxaloacetate to form citrate by citrate synthase in the 1st step of the Krebs cycle

net ATP in anaerobic conditions

2 ATP

net ATP in aerobic conditions

14 ATP (2 ATP + 4 NADH = 14 ATP)

where does the last step of aerobic glycolysis take place

inside mitochondria

where is glucokinase found

liver and pancreas

when does the liver remove large amounts of glucose from the blood

when blood glucose levels are high (2nd pass only)

where is hexokinase found

muscles and adipose

when does maximum hexokinase function occur

at normal blood glucose levels

does anything increase hexokinase function?

no

why is it good that hexokinase function cannot be increased

it prevents fatty muscle

why do we have such little fatty muscle

because nothing increases the function of hexokinase

what anaerobic glycolysis steps involve ATP

step 1: glucose → G6P (use up)

step 3: F6P → F1,6BisP (use up)

step 7: 1,3BPG → 3PG (produce)

step 10: PEP → pyruvate (produce)

what anaerobic glycolysis steps involve NADH

step 6: G3P → 1,3BPG (produces)

step 11: pyruvate → lactate (uses up)

what aerobic glycolysis steps involve ATP

step 1: glucose → G6P (use up)

step 3: F6P → F1,6BisP (use up)

step 7: 1,3BPG → 3PG (produce)

step 10: PEP → pyruvate (produce)

what aerobic glycolysis steps involve NADH

step 6: G3P → 1,3BPG (produces)

step 11: pyruvate → acetyl CoA (produces)

dehydrogenases tend to use what cofactor

NAD/NADH

kinases tend to use what cofactor

ATP/ADP

what do we do if there’s no oxaloacetate to combine with acetyl CoA and start Krebs cycle

pyruvate is converted to oxaloacetate by pyruvate carboxylase

2nd step in carbohydrate metabolism

Krebs Cycle (aka TCA, citric acid cycle)

what type of pathway is Krebs

amphibolic pathway

amphibolic pathway

carbs, fats, and proteins can all enter and be completely oxidized into CO2, H2O, and energy

provides precursors for synthesis pathways

amphibolic pathway example

Krebs

where does Krebs occur

mitochondrial matrix (inside)

products of Krebs

CO2, H2O, energy

how is CO2 excreted

exhaled by lungs

GTP → ATP equivalent

1 ATP

NADH → ATP equivalent

3 ATP

FADH → ATP equivalent

2 ATP

NADH and FADH are what type of cofactors

vitamins

B2 vitamin

FADH

B3 vitamin

NADH

why is there a discrepancy over whether Krebs produced 12 or 15 ATP per cycle

depends on if you technically begin the cycle with pyruvate (total 15 ATP) or acetyl CoA (total 12 ATP)

both are correct

total ATP produced from Krebs cycle starting with 2 acetyl CoA (1 glucose molecule)

24 ATP total

6 NADH (x3) = 18 ATP

2 FADH (x2) = 4 ATP

2 GTP (x1) = 2 ATP

18 + 4 + 2 = 24 ATP

total ATP produced from 1 glucose molecule under aerobic conditions

38 ATP total

Glycolysis:

2 ATP

4 NADH (x3) = 12 ATP

2 + 12 = 14 ATP

Krebs:

6 NADH (x3) = 18 ATP

2 FADH (x2) = 4 ATP

2 GTP (x1) = 2 ATP

18 + 4 + 2 = 24 ATP

Total:

24 + 14 = 38 ATP

why is there a discrepancy on whether 1 molecule of glucose produces 36 or 38 ATP?

depends on location in body:

36 in muscle

38 in liver

how many full Krebs cycles for 1 glucose molecule

2

1st step Krebs

acetyl CoA and oxaloacetate combine to form citrate by citrate synthase

step 1.5 Krebs

citrate converted to cis-aconitate by aconitase which is then converted to isocitrate again by aconitase

2nd step Krebs

citrate converted to isocitrate by aconitase

3rd step Krebs

isocitrate converted to a ketogluterate by isocitrate dehydrogenase

also forms NADH (NAD→NADH)

rate limiting enzyme of Krebs

isocitrate dehydrogenase

what is isocitrate dehydrogenase limited by

increased ATP, increased NADH

what is isocitrate dehydrogenase activated by

increased ADP, increased Ca2+

4th step Krebs

a ketogluterate converted to succinyl CoA by a ketogluterate dehydrogenase

also forms NADH (NAD→NADH)

5th step Krebs

succinyl CoA converted to succinate by succinyl CoA synthase

also produces 1 GTP molecule

6th step Krebs

succinate converted to fumarate by succinate dehydrogenase

also forms FADH (FAD→FADH)

7th step Krebs

fumarate converted to malate by fumarase

8th step Krebs

malate converted to oxaloacetate by malate dehydrogenase

also forms NADH (NAD→NADH)

the 2 shuttle systems

malate aspartate shuttle and glycerol 3 phosphate shuttle

malate aspartate shuttle function

moves cytosolic NADH (usually from glycolysis) into mitochondria → ETC

where does malate aspartate shuttle function

in cytosol and mitochondria in liver, kidney, heart

glycerol 3 phosphate shuttle function

converts cytosolic NADH (usually from glycolysis) to FADH to enter complex II of ETC

where does glycerol 3 phosphate shuttle function

in cytosol in muscle, brain

1st step malate aspartate shuttle

glyceraldehyde 3 phosphate converted to 1,3 bisphosphate uses NAD and produces NADH

2nd step of malate aspartate shuttle

oxaloacetate converted to malate using up NADH producing NAD (circles back to be used in first step)

3rd step of malate aspartate shuttle

malate enters mitochondria through mitochondrial membrane

4th step of malate aspartate shuttle

inside mitochondria, malate converted to oxaloacetate uses NAD and produces NADH

5th step of malate aspartate shuttle

inside mitochondria, NADH goes to complex I of ETC

malate function in electron transport

takes the hydrogens into mitochondria for NAD to be made into NADH for the ETC

1st step glyeraldehyde 3 phosphate shuttle

glyceraldehyde 3 phosphate converted to 1,3 bisphosphate uses NAD and produces NADH

2nd step glyeraldehyde 3 phosphate shuttle

DHAP converted to glycerol phosphate using up NADH producing NAD (circles back to be used in first step)

3rd step glyeraldehyde 3 phosphate shuttle

glycerol phosphate moves to membrane of complex II of ETC and exchanges with FAD to convert it to FADH

3rd step in carbohydrate metabolism

electron transport chain

electron transport chain function

production of mitochondrial ATP

important concepts of ETC

oxidation phosphorylation reactions, proton gradient, proton pump, electron transporters, ATP synthase

oxidation

loss of electrons or hydrogens

phosphorylation

addition of phosphorus

type of redox commonly used in ETC

uncoupling reactions

how does the proton gradient function

particles diffuse from an area of higher concentration to lower concentration

must maintain a higher concentration of protons in outer mitochondrial space

how does the proton pump function

complexes which remove electrons from coenzymes located in inner mitochondrial space and/or pump protons into the outer mitochondrial space

electron transporters function in ETC

transport electrons between complexes in the ETC