Oxidation of glucose

The complete oxidation of glucose into co2 and h20 has three main stages

1. Glycolysis + Pyruvate Dehydrogenase complex

2. TCA/ Citric Acid cycle

3. Electron transport chain

• we see oxidation in small steps

Where do the stages of glucose oxidation take place?

1. glycolysis + Pyruvate dehydrogenase - cytoplasm

2. TCA cycle → in mitochondria

3. ETC → inner mitochondrial membrane

How do organisms store glucose

animals store glucose as glycogen

plants store glucose as starch

What does glucose get converted into during glycolysis?

Pyruvate

What happens to pyruvate when there is no oxygen in human cells?

It is converted to lactate to regenerate NAD⁺.

What happens to pyruvate in yeast or plants under anaerobic conditions?

It is converted to acetaldehyde, then to ethanol.

Why is converting pyruvate to lactate or ethanol important under anaerobic conditions?

It regenerates NAD⁺, allowing glycolysis (and ATP production) to continue.

Charge of glucose and implications

glucose is a polar molecule, meaning it has an uneven distribution of charge.

• implication: because of its polarity it cannot pass through the lipid bilayer of the cell membrane by simple diffusion. BC the lipid bilayer is made up of fatty acids that are hydrophobic and repel polar moelcules.

If glucose is too polar to get into the cell after it was digested and entered bloodstream then how does it get in?

the body uses proteins called GLUTs (Glucose transporters embedded in the membrane to faciliatate the movement of glucose from the bloodstream into the cell

How does insulin help with glucose uptake?

It stimulates GLUT transporters to move glucose into cells.

What happens in diabetes regarding glucose transport?

Blood glucose is high, but it is not taken up into cells properly, causing the body to "starve" despite having plenty of glucose.

What is the only metabolic pathway that provides energy under anaerobic conditions?

Glycolysis

• fermentation doesnt produce ATP

Where does glycolysis occur?

in the cytosol of the cell

How many steps in glycolysis?

10 steps divided into 2 main phases

The 2 phases of glycolysis

1. Preparatory Phase (Steps 1–5):

2. Payoff Phase (Steps 6–10):

Prepratory phase

• Glucose is phosphorylated using 2 ATP

• Activate glucose.

• Enzymes like kinases are involved (a kinase adds a phosphate group).

Prep phase: STEP 1: Phosphorylation of Glucose

1. After glucose enters cell Hexokinase enzyme transfers a phosphate group from ATP to glucose forming ADP

2. The product is glucose-6-phosphate

Why? → this activates glucose and makes it more reactive

Isozymes

Isozymes are enzymes that catalyze the same chemical reaction but are encoded by different genes.

How many isozymes of hexokinase - the enzyme responsibel for phosphorylating glucose in step 1?

4 hexokinase (I-IV)

How do Hexokinase isozymes differ in their kinetics?

• Hexokinase I–III: Low KMK_MKM​ (~0.1 mM) → High affinity for glucose

• Hexokinase IV: High KMK_MKM​ (~8 mM) → Low affinity, only active when glucose is abundant (e.g., after meals)

PREP Phase step 2: Isomerization

The glucose ring opens rearranges and closes as a fructose ring.

• this step is catalyzed by phosphohexose isomerase

now called Fructose 6-phosphate

PREP Phase step 3: Second Phosphorylation

Phosphofructokinase-1 (PFK-1) adds a phosphate group from ATP to fructose 6-phosphate

• this creates fructose-1,6,bisphosphate with phosphate groups on two different carbons

• molecule is more symmetrical now

• ATP→ADP

Bisphosphate vs Diphosphate

Bisphosphate: has phosphates in 2 diff positions

Diphosphates: the phosphates are connected to one another

PREP PHASE step 4: Cleavage of fructose-1,6-bisphosphate

The enzyme aldose splits the 6 carbon fructose-1,6,-bisphosphate into two 3-carbon molecules:

• Glyceraldehyde-3-phosphate (G3P) (an aldose sugar)

• Dihydroxyacetone phosphate (DHAP) (a ketose sugar)

PREP PHASE step 5: Interconversion

Dihydroxyacetone phosphate (DHAP) is quickly converted to glyceraldehyde-3-phosphate (G3P) by the enzyme triose phosphate isomerase.

• This is an isomerization reaction that shifts the carbonyl group from the middle to the end to form an aldose

from this point forward we have two G3P molecules to proceed to the next phase

Payoff phase

Produces 2ATP and 2NADH and 2 pyruvate per glucose molecule

• produces these through substrate level phosphorylation and oxidation

PAYOFF PHASE step 1: phosphorylation and oxidation

G3P molecules are oxidized and the aldehyde group is converted into a carboxylic acid

• Nad+ is reduced to NADH

• Pi is added to phosphorylate

• the end result is a mixed anhydride (intermediate) called 1,3-bisphospholycertae (1,3-BPG)

per glucose moleucle (bc there were 2 G3P) we form 2 NADH from this step

• high energy

PAYOFF PHASE step 2: substrate level phosphorylation

1,3-bisphosphoglycerate (1,3-BPG) donates a phosphate group to ADP forming ATP

• result is 3-phosphoglycerate (more stable)

• this step generates 2 ATP bc there are two molecules

PAYOFF PHASE step 3": isomerization

Phosphoglycerate mutase (an isomerase) moves the phosphate group from the third carbon to the second carbon

• end result is 2-phosphoglycerate

PAYOFF PHASE Step 4: Dehydration

Enolase enzyme removes a water molecule from 2-phosphoglycerate

• this dehydration forms a new double bond

• End result is phosphoenolpyruvate (PEP) → a high energy molecule

PAYOFF STAGE step 5: Second substrate level phosphoylation

Phosphoenolpyruvate (PEP) donates its phosphate group to ADP forming ATP

• The product is pyruvate, which initially forms as enolpyruvate, a less stable form.

• Enolpyruvate tautomerizes (spontaneously shifts) to ketopyruvate, the more stable form.

• produces 2 ATP and 2 pyruvate.

X is an inhibitor of the enzyme phosphoglycerate mutase. In an anaerobic system that is metabolizing glucose as a substrate, which of the following compound would you expect to accumulate, following addition of X?

A. glucose-6-phosphate

B. phospho-enol-pyruvate

C. 3-phosphoglycerate

D. 2-phosphoglycerate

E. Glyceraldehyde 3-phosphate

If we have a chain and 3 enzymes to catalyze each reaction, what would happen if we inhibited enzyme 2? Wed get a build up of b and well get less of C and D

so we know that at the payoff step mutase isomerizes the 3-phosphoglycerate to produce 2-phosphoglycerate - if mutase becomes an inhibitor than the molecule its supposed to function on will accumulate

• answer: 3-phosphoglycerate

The first reaction in glycolysis that results in the formation of an energy-rich compound (i.e., a compound whose hydrolysis has a highly negative ΔG'°) is catalyzed by:

A. glyceraldehyde 3-phosphate dehydrogenase

B. hexokinase

C. phosphofructokinase-1

D. triose phosphate isomerase

A

• we know this bc. its the first reaction to result in somethign energy rich like NADH