202 Carbohydrates And Structure Of It, Lipid Metabolism(structure Is Somewhere Else In This Class But Not This Deck) Flashcards
Glycolysis has how many steps in its process?
Which part of the cell does it occur in?
Is it an anabolic or catabolic process ?
There are three types of chemical transformations in glycolysis, state them.
There are two phases in glycolysis, state them.
Which parts or cells in the body are completely glycolysis dependent
How many carbons does glucose have?
What about pyruvate?
A ten-step universal process (cytosolic)
•Three types of chemical transformations
–Degradation of carbon skeleton of glucose
–Phosphorylation of ADP
–Transfer of hydride ion to NAD
•Two phases
•Preparatory (investment)
•Payoff
(erythrocyte, renal medulla, sperm, brain)-dependent
Glucose is 6
Pyruvate is 3
Why are erythrocytes, renal medulla, sperm, and brain glycolysis-dependent?
State four functions of glycolysis
Warburg effect: cancer cells produce lactic acid from aerobic glycolysis. So even if there’s plenty oxygen, they’ll still produce lactic acid from aerobic not anaerobic glycolysis
Great questions! Here’s a simple breakdown:
Why are erythrocytes, renal medulla, sperm, and brain glycolysis-dependent?
1. Erythrocytes (Red Blood Cells)
• No mitochondria, so they can’t use the Krebs cycle or ETC.
• Rely 100% on glycolysis for ATP.
2. Renal Medulla (inner part of the kidney)
• Has low oxygen supply, especially in the medulla.
• Uses anaerobic glycolysis to survive and function. Since the renal medulla often works in low oxygen, it uses anaerobic glycolysis, which produces lactate.
• This lactate can then travel to the liver, where it’s reused in gluconeogenesis (Cori cycle).
• So, the body recycles it instead of letting it build up.
3. Sperm cells
• Need rapid, mobile energy.
• Rely heavily on glycolysis, especially when in low-oxygen areas like the female reproductive tract.
4. Brain
• High energy demand and prefers glucose.
• Though it uses oxygen, in emergencies or early development, it also relies on glycolysis.
Importance of Glycolysis in Different Contexts:
1. Fertility
• Glycolysis powers sperm motility.
• Without glycolysis, sperm can’t move properly to fertilize the egg. You’re right — sperm prefer fructose as an energy source, especially in seminal fluid. Here’s how it fits with glycolysis:
Why sperm use fructose:
• The seminal vesicles secrete fructose, which becomes the main sugar available to sperm after ejaculation.
• Fructose enters glycolysis just like glucose, but at a later step (after being converted to fructose-6-phosphate or fructose-1-phosphate, depending on the pathway).
So, do sperm still rely on glycolysis?
Yes!
• Sperm use glycolysis to break down fructose and generate ATP.
• This ATP powers the flagella (tail) for motility — crucial for reaching and fertilizing the egg.
Summary:
Sperm use fructose instead of glucose, but still depend on glycolysis to break it down and produce energy for movement.
Let me know if you want a quick flowchart on how fructose enters glycolysis.
2. Erythrocyte Integrity • Glycolysis gives ATP to maintain ion balance and cell membrane shape. • Without it, red cells become fragile and break down (hemolysis). ATP maintains the ion pumps. Great question!
Here’s the simple explanation:
Red blood cells (erythrocytes) need to maintain a balance of sodium (Na⁺) and potassium (K⁺) using the Na⁺/K⁺ ATPase pump. This pump uses ATP to:
• Push out 3 Na⁺ ions
• Pull in 2 K⁺ ions
How this keeps the biconcave shape:
1. Prevents water overload:
If too much Na⁺ stays inside the cell, water follows (osmosis) and the cell swells.
Swelling rounds the cell and destroys the biconcave shape.
2. Maintains flexibility:
The biconcave shape helps red blood cells squeeze through capillaries.
If ion balance is off, the cell becomes stiff or spherical, which leads to early destruction (hemolysis).
In summary:
ATP-powered ion balance prevents swelling and keeps the red blood cell’s flexible, biconcave shape intact.
3. Energy Supply
• Glycolysis is fast and doesn’t require oxygen.
• Vital during low oxygen conditions or intense activity.
4. Cancer
• Cancer cells prefer glycolysis even in the presence of oxygen (Warburg effect).
• It helps them grow fast and survive in low-oxygen tumors. Cancer cells prefer glycolysis for energy, even when oxygen is present (this is unusual).
• They make less ATP per glucose, but do it very fast.
• This helps them:
• Grow quickly
• Survive in low-oxygen tumors
• Make building blocks for new cells
Let me know if you want this turned into a chart or flashcards!
State the steps of glycolysis
Preparatory stage(from phosphorylation of glucose glyceraldehyde 3-phosphate)
So phosphate is added to glucose via ATP and the products are glucose 6 phosphate and ADP. This occurs via hexokinase.
Then glucose 6 phosphate is converted to fructose 6 phosphate(ketose and has a five membered ring just that the phosphate group is on the sixth carbon) via phosphoglucose isomerase.(Phosphohexose isomerase(also called glucose-6-phosphate isomerase or phosphoglucose isomerase — all are used interchangeably)
Then a phosphate is added again to form fructose 1,6 bis phosphate(the phosphate is on the first and another on the 6th carbon) via the enzyme phosphofructokinase-1. This is the rate limiting step. The enzyme is induced when there is high AMP and low ATP. High AMP shows there’s low ATP.(Can AMP and ATP both be high at the same time?Not usually.
They usually have an inverse relationship because:
• ATP is constantly being used, and when it breaks down:
• ATP → ADP → AMP
• So if ATP is high, AMP is usually low
• If AMP is high, it means ATP has been used up
So fructose 1,6 bisphosphate is cleaved or broken into two by aldolase to form Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate(both 3 carbons)
Dihydroxyacetone phosphate is converted into gycleraldehydye 3-phosphate by triose phosphate isomerase
This ends the preparatory phase
So at the end of this phase, you use up 2 ATP to produce 2glyceradehyde 3-phosphate (G3P) and 2ADP
Payoff phase(now you have money to pay off your debt of using 2ATP)
The 2 G3Ps are converted to 1,3bisphosphoglycerate at the same time by glyceraldehyde 3-phosphate dehydrogenase.
This occurs by removal of hydrogen from carbon 1 of G3P during the oxidation, and transfering it to NAD⁺, reducing it to NADH. Because the step where G3P becomes 1,3-BPG is an oxidation (Once G3P is oxidized, it gives a hydride ion (H⁻) to NAD⁺) reaction electrons are being removed.But electrons can’t just float around.You need something to accept them. That’s NAD⁺. So a reduction, oxidation and phosphorylation(from an inorganic phosphate from somewhere) is occurring here. So you get two 1,3BPG and 2 NADH+ and 2 H+ (just released from the reaction)
Term,Explanation
Oxidation,G3P’s aldehyde group is oxidized to an acid (loses electrons).
Reduction,NAD⁺ gains electrons and a proton → becomes NADH.
1,3-BPG,Has 2 phosphates: one on carbon 1 (added), one on carbon 3 (already there). It’s no longer an aldehyde but a carboxylic acid derivative, so it’s called “glycerate”, not “glyceraldehyde”.
So now the phosphate group on the first carbon of 1,3bisphosphoglycerate is very unstable and eager to donate itself so it does so to the ADP from the preparatory phase to form ATP. So now we have only one phosphate on the third carbon making it 3-phosphoglycerate(or 3PG) (Remember this is happening for the two G3Ps so we actually have 2 of the 3-PG)
This is facilitated by the enzyme phosphoglycerate kinase(kinase means an enzyme that does phosphorylation) .
So at the end of this, we have 2 of the 3PG and we have 2ATP.
This is the first substrate-level phosphorylation step in glycolysis — meaning ATP is made directly from a high-energy substrate (1,3-BPG).
3PG is way too stable so it wouldn’t want to make the phosphoenolpyruvate(PEP) so you have to convert it to 2PG and this is done via phosphoglycerate mutase.
Then 2PG (phosphate is on the second carbon) is converted to PEP via enolase by the removal of water from the 2PG to create a high energy double bond. So PEP means it has a phosphate, the enol means the double bond created and pyruvate is for the next step I guess.
And PEP is converted to pyruvate via pyruvate kinase by removing phosphate from the PEP and adding it to ADP to form ATP. This is the second substrate level phosphorylation
There’s a large pool of ADP in every cell — not just 2 molecules. Think of ADP and ATP as recycled currency — they are constantly being used and regenerated in all parts of the cell. So it’s a different set of ADp that was brought here. It came from the same cytoplasmic pool of ADP or from the cell’s existing supply of ADP.
The enol form in PEP is unstable.
• After losing phosphate (to make ATP), it becomes enol-pyruvate.
• Then it spontaneously changes (tautomerizes) to the keto form of pyruvate, which is much more stable.
• This helps make the reaction highly exergonic (releases a lot of energy).
If a reaction is highly exergonic, it means that Gibbs free energy (ΔG) is very negative.
• Exergonic means the reaction releases energy.
• A very negative ΔG means the reaction is spontaneous and gives off a lot of free energy.
Simple:
→ Highly exergonic = ΔG very negative = reaction happens easily and releases energy.
Would you like a quick example too? It moves to the right.
When a reaction is highly exergonic (very negative ΔG), it strongly favors the formation of products, so it proceeds toward the right.
Simple:
→ Highly exergonic → moves to the right → more products formed.
Would you also like me to explain it with a tiny visual in words? (like a mini diagram?)
If it’s endergonic (positive ΔG), it favors the formation of reactants.
Simple:
→ Endergonic → moves left → more reactants.
Because the reaction needs energy input and naturally prefers to stay where it started (at the reactants).
Want me to also give you a super quick trick to remember both at once?
Explain how these sugars enter the glycolytic pathway; fructose, sucrose, glycogen or starch , mannose, galactose,trehalose, lactose
Great! Let’s walk through each sugar’s journey—step by step—until it meets the main glycolysis pathway. I’ll keep it clear and logical without a chart, as requested.
- Trehalose
• Trehalose = Glucose–Glucose (α-1,1 linkage)
• Enzyme: Trehalase
→ Breaks trehalose into 2 glucose molecules
• Each glucose:
→ Hexokinase phosphorylates glucose to glucose-6-phosphate
→ Enters glycolysis at the second step - Lactose
• Lactose = Glucose + Galactose
• Enzyme: Lactase
→ Breaks lactose into glucose and galactose
• Glucose → Same as above
• Galactose pathway:- Galactose → Galactose-1-phosphate (via galactokinase)
- Galactose-1-P + UDP-glucose → UDP-galactose + glucose-1-phosphate (via GALT)
- Glucose-1-phosphate → Glucose-6-phosphate (via phosphoglucomutase)
→ Now it joins glycolysis at the second step
Great questions! Let’s break them down clearly, step by step. We’ll cover:
1. Galactose Step 2: Galactose-1-P + UDP-glucose
2. What is UDP-glucose? Where does it come from?
3. Glycogen breakdown (including alpha-amylase and phosphoglucomutase)
4. How these enter glycolysis
- Galactose Step 2 (Confusing but simple when broken down)
Galactose-1-phosphate + UDP-glucose → UDP-galactose + Glucose-1-phosphate
• Enzyme: Galactose-1-phosphate uridylyltransferase (GALT)
• What happens:
• UDP-glucose donates a UDP group to galactose-1-P.
• Galactose now carries the UDP, becoming UDP-galactose.
• Glucose is left behind as glucose-1-phosphate.
So it’s like a “swap” of UDP from glucose to galactose.
- What is UDP-glucose? Where did it come from?
• UDP-glucose = Uridine diphosphate glucose
• It’s a “charged” form of glucose, used as a glucose donor in many reactions (like glycogen synthesis).
• It’s made from:
• Glucose-1-phosphate + UTP → UDP-glucose + PPi
• Enzyme: UDP-glucose pyrophosphorylase
So, the cell uses UDP-glucose as a helper molecule to allow galactose to enter the pathway properly.
- Glycogen Breakdown
There are two paths, depending on the enzyme:
a. Glycogen phosphorylase pathway (main one)
• Enzyme: Glycogen phosphorylase
• It cleaves glucose off glycogen by adding phosphate (not water)
• Glycogen (n residues) → Glycogen (n-1) + Glucose-1-phosphate
• G-1-P is then converted to G-6-P via phosphoglucomutase
→ G-6-P enters glycolysis
b. Alpha-amylase pathway (in digestion, not muscle/liver)
• Alpha-amylase breaks glycogen randomly at α-1,4 bonds
• Makes maltose, maltotriose, and limit dextrins
• Then other enzymes (e.g., maltase, isomaltase) finish breaking them into free glucose
• Free glucose → Hexokinase converts it to G-6-P → enters glycolysis
So:
• In tissues (e.g., muscle, liver) → glycogen phosphorylase
• In digestive tract → alpha-amylase and maltase pathway
- What does phosphoglucomutase do?
• Converts glucose-1-phosphate → glucose-6-phosphate
• It moves the phosphate from carbon 1 to carbon 6
• Mechanism:
• Uses a temporary phosphorylated enzyme intermediate to help move the phosphate group around
• This G-6-P now continues through glycolysis (step 2)
In summary:
• Galactose needs help: UDP-glucose swaps the UDP onto galactose so it becomes UDP-galactose and glucose-1-phosphate enters glycolysis.
• UDP-glucose is a helper molecule made from G-1-P + UTP.
• Glycogen can break down via:
• Glycogen phosphorylase → G-1-P → G-6-P → glycolysis
• Alpha-amylase (in digestion) → glucose → G-6-P → glycolysis
• Phosphoglucomutase just shifts the phosphate from C1 to C6
Let me know which part you want simplified even more!
- Sucrose
• Sucrose = Glucose + Fructose
• Enzyme: Sucrase
→ Breaks sucrose into glucose and fructose
a. Glucose
• Hexokinase converts it to glucose-6-phosphate → glycolysis
b. Fructose
In muscle/adipose tissue (where hexokinase works):
• Fructose → Fructose-6-phosphate (via hexokinase)
→ Enters glycolysis before the PFK-1 step
In liver (where fructokinase dominates):
1. Fructose → Fructose-1-phosphate (via fructokinase)
2. Fructose-1-phosphate → Glyceraldehyde + DHAP (via aldolase B)
3. DHAP → Directly into glycolysis
4. Glyceraldehyde → G3P (via triose kinase)
→ Both DHAP and G3P are now in the payoff phase of glycolysis
- Glycogen
• Glycogen = Branched glucose storage polymer
• Enzyme: Glycogen phosphorylase
→ Removes glucose as glucose-1-phosphate
• Glucose-1-phosphate → Glucose-6-phosphate (via phosphoglucomutase)
→ Enters glycolysis at the second step - Mannose
• Mannose is a structural isomer of glucose- Hexokinase: Mannose → Mannose-6-phosphate
- Phosphomannose isomerase: Mannose-6-phosphate → Fructose-6-phosphate
→ Joins glycolysis just before PFK-1
- Galactose
[Already explained under Lactose above, but here’s a recap:]
1. Galactose → Galactose-1-P (via galactokinase)
2. Gal-1-P + UDP-glucose → Glu-1-P + UDP-galactose (via GALT)
3. Glu-1-P → Glu-6-P (via phosphoglucomutase)
→ Enters glycolysis
- Fructose
• In muscle:
Fructose → Fructose-6-phosphate (via hexokinase) → glycolysis before PFK-1
• In liver:- Fructose → Fructose-1-phosphate (fructokinase)
- Fructose-1-P → Glyceraldehyde + DHAP (aldolase B)
- Glyceraldehyde → G3P (triose kinase)
→ DHAP and G3P both continue into glycolysis
Summary of where they all meet glycolysis:
• Glucose-6-phosphate: Trehalose, lactose (via glucose or galactose), glycogen, galactose
• Fructose-6-phosphate:mannose, fructose (in muscle)
• Fructose-1-phosphate → DHAP + G3P: Fructose (in liver)
• G3P and DHAP: Direct entry into payoff phase
Yes — mainly fructose does this shortcut through fructose-1-phosphate in the liver.
No other common sugar bypasses PFK-1 like fructose does.
Here’s the breakdown:
• Glucose:
• Goes through glucose-6-phosphate → fructose-6-phosphate → (then PFK-1 acts) → fructose-1,6-bisphosphate.
(Normal PFK-1 control applies.)
• Galactose:
• Converted to glucose-1-phosphate → glucose-6-phosphate → (normal glycolysis path).
(Normal PFK-1 control applies.)
• Mannose:
• Converted to fructose-6-phosphate → (normal glycolysis path).
(Normal PFK-1 control applies.)
• Fructose (muscle):
• Becomes fructose-6-phosphate directly → (normal PFK-1 step).
(Normal PFK-1 control applies.)
• Fructose (liver):
• Becomes fructose-1-phosphate → DHAP + glyceraldehyde → bypasses PFK-1.
(No PFK-1 control!)
Simple rule:
Only liver fructose skips PFK-1. Everything else obeys PFK-1.
Would you want a super tiny flowchart visual too? (It makes this even easier to lock into memory!)
You’re asking a very smart and important question. Let’s break it down slowly:
Normally:
• In glycolysis, PFK-1 acts as a “gatekeeper.”
• It controls how fast glucose is broken down based on the body’s needs (energy demand).
• If the body already has enough ATP, PFK-1 slows down, and glucose metabolism slows too.
→ PFK-1 = “energy checkpoint”
But with fructose in the liver:
• Fructose bypasses PFK-1.
• It cannot be slowed down by ATP levels or energy needs.
• Fructose is broken down whether or not the body needs energy.
• Its carbons flood into the later parts of glycolysis unchecked.
What happens when there’s too much fructose?
• The glycolysis “payoff phase” gets overloaded with intermediates like DHAP and glyceraldehyde.
• These extra carbons are then rerouted to make fats (lipogenesis).
• The liver converts the excess carbons into fatty acids and triglycerides for storage.
In short:
• Fructose metabolism is fast and out of control in the liver.
• Excess fructose easily becomes fat, contributing to fatty liver disease and obesity.
Simple version for you:
Because fructose skips PFK-1, it keeps entering glycolysis even when the body is “full,” and the extra carbon ends up being stored as fat.
Would you also want me to show a quick path from fructose to fat (in just 4 simple steps)? It’s cool and very fast to memorize!
Let me know if you’d like a quick visual or just a story-style summary!
State the inhibitors of glycolysis and the specific steps they inhibit
Sure! Here are 10 USMLE-style MCQs on glycolysis — no answers included, just the questions:
- A patient is given a compound that inhibits phosphofructokinase-1 (PFK-1). Which of the following changes is most likely to be observed in glycolysis?
A. Accumulation of fructose 1,6-bisphosphate
B. Increased pyruvate production
C. Decreased glucose 6-phosphate levels
D. Accumulation of fructose 6-phosphate - Which enzyme of glycolysis is bypassed when arsenate replaces inorganic phosphate during the pathway?
A. Hexokinase
B. Glyceraldehyde-3-phosphate dehydrogenase
C. Pyruvate kinase
D. Phosphoglycerate kinase - A patient exposed to fluoride shows decreased ATP production in glycolysis. Which enzyme is most likely inhibited?
A. Enolase
B. Aldolase
C. Pyruvate kinase
D. Hexokinase - Which of the following conditions would increase the activity of phosphofructokinase-1?
A. High ATP concentration
B. High citrate levels
C. High AMP concentration
D. High glucose 6-phosphate - A mutation that decreases pyruvate kinase activity would have which of the following direct consequences in the glycolytic pathway?
A. Increased NADH production
B. Increased phosphoenolpyruvate (PEP) levels
C. Increased ATP formation
D. Increased glucose uptake - A 4-year-old boy has an inborn error in glycolysis that causes hemolytic anemia. Which of the following enzymes is most likely deficient?
A. Enolase
B. Hexokinase
C. Pyruvate kinase
D. Phosphoglycerate mutase - Which of the following best describes the role of NAD+ in glycolysis?
A. Oxidizes ATP to ADP
B. Phosphorylates glucose
C. Accepts electrons from glyceraldehyde-3-phosphate
D. Converts phosphoenolpyruvate to pyruvate - During glycolysis, aldolase cleaves which of the following substrates?
A. Glucose
B. Fructose 6-phosphate
C. Fructose 1,6-bisphosphate
D. Glyceraldehyde 3-phosphate - Which of the following enzymes catalyzes a reversible reaction in glycolysis?
A. Hexokinase
B. Phosphofructokinase-1
C. Pyruvate kinase
D. Phosphoglycerate mutase - Which glycolytic intermediate directly donates a phosphate group to ADP to form ATP?
A. Glucose 6-phosphate
B. 1,3-bisphosphoglycerate
C. Glyceraldehyde 3-phosphate
D. Fructose 1,6-bisphosphate
Let me know when you’re ready for the correct answers with explanations!
Inhibitors of Glycolysis
- Arsenate (AsO₄³⁻)
• Mimics inorganic phosphate (Pi)
• During the step:
Glyceraldehyde-3-phosphate → 1,3-bisphosphoglycerate,
it forms 1-arseno-3-phosphoglycerate instead.
• Problem: This product is unstable, breaks down without producing ATP
• Net effect: Bypasses ATP production → less energyThink: Arsenate steals the phosphate slot → no ATP made
You’re thinking really well — let’s go through it carefully and clearly, piece by piece:
First: Arsenate in Glycolysis
Normal glycolysis (without arsenate):
• G3P (glyceraldehyde-3-phosphate)
→ (via G3P dehydrogenase) →
1,3-bisphosphoglycerate (1,3-BPG) (high-energy molecule)
→ (via phosphoglycerate kinase) →
3-phosphoglycerate + ATP
KEY:
• 1,3-BPG donates phosphate to ADP → makes ATP.
With arsenate (instead of normal Pi):
• G3P reacts with arsenate instead of Pi.
• This makes 1-arseno-3-phosphoglycerate (NOT 1,3-BPG).
• Problem: 1-arseno-3-phosphoglycerate is very unstable and breaks down immediately into 3-phosphoglycerate — without making ATP.
Summary:
Arsenate tricks G3P dehydrogenase to make a fake product. Because it’s unstable, it falls apart before phosphoglycerate kinase can even act. → No ATP is made at this step!
Important clarification:
• 2,3-bisphosphoglycerate (2,3-BPG) is different.
• It’s made in red blood cells, not normal glycolysis, by a special side path (the Rapoport-Luebering shunt).
• In normal glycolysis, the important molecule is 1,3-bisphosphoglycerate donating phosphate to ADP.
Why doesn’t arsenate’s product donate phosphate?
• 1-arseno-3-phosphoglycerate is so unstable that it hydrolyzes (falls apart) spontaneously before an enzyme (like phosphoglycerate kinase) can even use it.
• It just “dissolves” into 3-phosphoglycerate without giving phosphoglycerate kinase the chance to make ATP.
Second: Why does citrate inhibit PFK-1?
Simple answer:
Citrate signals that the cell already has plenty of energy and building blocks.
So, there’s no need to break down more glucose.
How?
• Citrate is an intermediate from the TCA cycle.
• If it builds up, it allosterically inhibits PFK-1 (binds at a site other than the active site).
• This slows down glycolysis at the PFK-1 step, so the cell doesn’t waste glucose.
Visual summary:
High citrate = “We have enough!” → PFK-1 slows down → glycolysis slows.
Would you like a very tiny cheat-table summarizing all PFK-1 inhibitors and activators? (It’s only about 5 bullets and super helpful!)
- Fluoride (F⁻)
• Inhibits enolase, which converts:
2-phosphoglycerate → phosphoenolpyruvate (PEP)
• Stops glycolysis before final ATP-producing stepsUsed in blood collection tubes to preserve glucose levels (prevents glycolysis) - Iodoacetate
• Inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
• Blocks:
G3P → 1,3-bisphosphoglycerate
• Stops NADH production and ATP generation that followThink: Iodoacetate blocks the first oxidation step in the payoff phase
How Arsenate Disrupts Glycolysis:
Normal Step:
• Enzyme: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
• Reaction:
\text{G3P + Pi + NAD⁺} \rightarrow \text{1,3-bisphosphoglycerate (1,3-BPG) + NADH + H⁺}
With Arsenate (AsO₄³⁻):
• Arsenate resembles Pi and competes with it.
• Instead of forming 1,3-BPG, the enzyme forms 1-arseno-3-phosphoglycerate.
• This compound is unstable and undergoes spontaneous hydrolysis to form 3-phosphoglycerate, bypassing ATP generation.
Consequence:
• Normally, 1,3-BPG donates a phosphate to ADP (via phosphoglycerate kinase) to generate ATP.
• In presence of arsenate: No ATP is formed from this reaction → “energy theft”.
Other Important Glycolysis Inhibitors:
Inhibitor Target Enzyme Effect
Arsenate (As⁵⁺) GAPDH (competes with Pi) No ATP from 1,3-BPG step
Fluoride (F⁻) Enolase Blocks PEP formation; used in blood glucose testing
Iodoacetate GAPDH (binds –SH group) Stops NADH and 1,3-BPG formation
Mercury ions (Hg²⁺) GAPDH (binds thiol groups) Like iodoacetate, inhibits via sulfhydryl disruption
Mannoheptulose Hexokinase/Glucokinase Prevents glucose phosphorylation
2-Deoxyglucose Traps glucose as G6P analog Blocks further metabolism of glucose
Citrate Inhibits PFK-1 Feedback inhibition from TCA cycle
ATP Inhibits PFK-1 Energy signal to slow glycolysis
Glucagon ↓ PFK-2 activity → ↓ F2,6BP → ↓ PFK-1 Slows glycolysis in liver
Acidosis Inhibits Pyruvate kinase (in muscle) Protective mechanism
Great! Here are the 10 USMLE-style MCQs on glycolysis again — now with correct answers and explanations:
- A patient is given a compound that inhibits phosphofructokinase-1 (PFK-1). Which of the following changes is most likely to be observed in glycolysis?
Answer: D. Accumulation of fructose 6-phosphate
Explanation: PFK-1 catalyzes the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate. Inhibition leads to an accumulation of fructose 6-phosphate and decreased glycolytic flux. - Which enzyme of glycolysis is bypassed when arsenate replaces inorganic phosphate during the pathway?
Answer: D. Phosphoglycerate kinase
Explanation: Arsenate competes with Pi at the glyceraldehyde-3-phosphate dehydrogenase step to form 1-arseno-3-phosphoglycerate. This compound is unstable and breaks down spontaneously to 3-phosphoglycerate, bypassing the ATP-producing phosphoglycerate kinase step. Result: No ATP is produced. - A patient exposed to fluoride shows decreased ATP production in glycolysis. Which enzyme is most likely inhibited?
Answer: A. Enolase
Explanation: Fluoride inhibits enolase, the enzyme that converts 2-phosphoglycerate to phosphoenolpyruvate (PEP), a high-energy intermediate necessary for ATP generation. - Which of the following conditions would increase the activity of phosphofructokinase-1?
Answer: C. High AMP concentration
Explanation: AMP is an allosteric activator of PFK-1, signaling low energy status and promoting glycolysis. High ATP and citrate inhibit it. - A mutation that decreases pyruvate kinase activity would have which of the following direct consequences in the glycolytic pathway?
Answer: B. Increased phosphoenolpyruvate (PEP) levels
Explanation: Pyruvate kinase converts PEP to pyruvate. A deficiency causes PEP accumulation and decreased ATP formation, especially affecting RBCs. - A 4-year-old boy has an inborn error in glycolysis that causes hemolytic anemia. Which of the following enzymes is most likely deficient?
Answer: C. Pyruvate kinase
Explanation: Pyruvate kinase deficiency is a known cause of hemolytic anemia due to reduced ATP, which is vital for maintaining RBC membrane integrity. - Which of the following best describes the role of NAD+ in glycolysis?
Answer: C. Accepts electrons from glyceraldehyde-3-phosphate
Explanation: NAD+ acts as an electron acceptor in the oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, producing NADH. - During glycolysis, aldolase cleaves which of the following substrates?
Answer: C. Fructose 1,6-bisphosphate
Explanation: Aldolase splits fructose 1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). - Which of the following enzymes catalyzes a reversible reaction in glycolysis?
Answer: D. Phosphoglycerate mutase
Explanation: Phosphoglycerate mutase catalyzes the reversible conversion of 3-phosphoglycerate to 2-phosphoglycerate. The irreversible steps are catalyzed by hexokinase, PFK-1, and pyruvate kinase. - Which glycolytic intermediate directly donates a phosphate group to ADP to form ATP?
Answer: B. 1,3-bisphosphoglycerate
Explanation: 1,3-BPG donates a high-energy phosphate to ADP via phosphoglycerate kinase, forming ATP and 3-phosphoglycerate — an example of substrate-level phosphorylation.
Want more questions or need simplified flashcards from these?
10 USMLE-Style MCQs on Glycolysis
1.
A scientist is studying glycolysis and adds arsenate to a sample. Which of the following changes would most likely be observed?
A. Increased NADH production
B. Increased ATP production
C. Unchanged NADH production, decreased ATP yield
D. Accumulation of fructose-1,6-bisphosphate
E. Increased activity of enolase
Answer: C
Explanation: Arsenate replaces Pi at the GAPDH step → NADH still made, but ATP step is bypassed.
2.
Fluoride inhibits which enzyme in glycolysis, and what is the result of its inhibition?
A. Enolase; accumulation of 2-phosphoglycerate
B. Hexokinase; glucose remains unphosphorylated
C. GAPDH; no NADH formed
D. PFK-1; decreased F-1,6-BP
E. Pyruvate kinase; increased PEP levels
Answer: A
Explanation: Fluoride inhibits enolase, leading to 2-PG buildup.
3.
A toxin binds to sulfhydryl groups and inhibits GAPDH. Which metabolite will accumulate?
A. Phosphoenolpyruvate
B. Fructose-1,6-bisphosphate
C. Glyceraldehyde-3-phosphate
D. Pyruvate
E. 3-phosphoglycerate
Answer: C
Explanation: GAPDH is blocked → G3P accumulates.
4.
Which of the following enzymes is inhibited by ATP as a feedback mechanism in glycolysis?
A. Hexokinase
B. GAPDH
C. Phosphofructokinase-1
D. Enolase
E. Pyruvate kinase
Answer: C
Explanation: ATP allosterically inhibits PFK-1 → controls glycolysis pace.
5.
Which step in glycolysis directly produces ATP via substrate-level phosphorylation?
A. Glucose → G6P
B. F-6-P → F-1,6-BP
C. 1,3-BPG → 3-PG
D. PEP → Pyruvate
E. G3P → 1,3-BPG
Answer: C and D (both are correct)
Explanation: Both steps produce ATP via substrate-level phosphorylation.
6.
Which enzyme is responsible for converting PEP to pyruvate with concurrent ATP production?
A. Enolase
B. Pyruvate kinase
C. PFK-1
D. Hexokinase
E. GAPDH
Answer: B
Explanation: Pyruvate kinase catalyzes the last step → ATP + pyruvate.
7.
Which glycolytic intermediate is a high-energy molecule and donates phosphate to ADP?
A. Glucose-6-phosphate
B. Fructose-1,6-bisphosphate
C. 3-phosphoglycerate
D. Phosphoenolpyruvate
E. Dihydroxyacetone phosphate
Answer: D
Explanation: PEP is the highest-energy intermediate in glycolysis.
8.
A patient has a deficiency in aldolase. Which metabolic intermediate will accumulate?
A. Fructose-6-phosphate
B. Fructose-1,6-bisphosphate
C. G3P
D. Pyruvate
E. Lactate
Answer: B
Explanation: Aldolase splits F-1,6-BP into G3P and DHAP → deficiency = F-1,6-BP buildup.
9.
2-Deoxyglucose is a glucose analog that is phosphorylated but cannot be further metabolized. What is the likely result?
A. Inhibition of glucose transport
B. Inhibition of hexokinase
C. Accumulation of 2-deoxyglucose-6-phosphate
D. Activation of enolase
E. Enhanced ATP generation
Answer: C
Explanation: 2-DG gets trapped as 2-DG-6P, halting glycolysis early.
10.
A researcher adds iodoacetate to a cell extract. Which enzyme is targeted and which key cofactor will not be reduced?
A. Enolase; FAD
B. GAPDH; NAD⁺
C. Pyruvate kinase; NADH
D. PFK-1; ATP
E. Hexokinase; G6P
Answer: B
Explanation: Iodoacetate blocks GAPDH → no NADH produced.
Explain the 2,3bisphosphate pathway and how it’s helpful for erythrocytes
- 2,3-Bisphosphoglycerate (2,3-BPG) Pathway in Erythrocytes
What it is:
• A side pathway (also called the Rapoport-Luebering shunt) that branches off from glycolysis in red blood cells (RBCs).
• It bypasses the ATP-producing step catalyzed by phosphoglycerate kinase.
How it works:
1. In glycolysis, 1,3-bisphosphoglycerate (1,3-BPG) usually donates a phosphate to ADP to make ATP and 3-phosphoglycerate (3-PG).
2. In erythrocytes, an enzyme called bisphosphoglycerate mutase converts 1,3-BPG → 2,3-BPG instead.
3. 2,3-BPG can then be converted to 3-PG by 2,3-BPG phosphatase, rejoining glycolysis — but no ATP is formed in this detour.
Why it helps RBCs:
• 2,3-BPG binds to hemoglobin and reduces its affinity for oxygen.
• This promotes oxygen release to tissues, which is critical in low-oxygen environments (e.g. muscles or high altitudes).
2,3-BPG helps RBCs by making sure hemoglobin lets go of oxygen in the tissues.
To clarify this:
2,3-bisphosphoglycerate (2,3-BPG) doesn’t directly bypass phosphoglycerate kinase (PGK) in the normal glycolysis pathway. Instead, 2,3-BPG is an intermediate that diverts from the regular glycolytic flow at a side step and has a separate purpose.
Here’s how it works:
Normal glycolysis flow:
1. G3P (glyceraldehyde-3-phosphate) → 1,3-BPG (via G3P dehydrogenase)
2. 1,3-BPG → 3-phosphoglycerate (via phosphoglycerate kinase)
3. 3-phosphoglycerate continues down glycolysis toward pyruvate and ATP generation.
When 2,3-BPG is formed:
• In red blood cells, an alternative pathway (the Rapoport-Luebering shunt) creates 2,3-BPG from 1,3-BPG.
• 2,3-BPG is formed from 1,3-BPG by the enzyme bisphosphoglycerate mutase.
• The purpose of 2,3-BPG is not to continue glycolysis as normal but to regulate oxygen release from hemoglobin in red blood cells.
Why doesn’t it need phosphoglycerate kinase?
• Once 2,3-BPG is formed, it does not continue to 3-phosphoglycerate (which would need phosphoglycerate kinase).
• Instead, it directly helps regulate oxygen binding to hemoglobin (affecting oxygen release to tissues).
• After 2,3-BPG is used in this way, it is then converted back to 3-phosphoglycerate by the enzyme bisphosphoglycerate phosphatase, which allows the glycolytic pathway to continue.
Key point:
2,3-BPG doesn’t bypass PGK in a direct sense. It simply diverts from the normal glycolysis path and serves a regulatory role. Once it fulfills its purpose, glycolysis continues with the generation of ATP from 3-phosphoglycerate.
Would you like a quick recap of the Rapoport-Luebering shunt, or is this enough for now?
Why is this important?
• 2,3-BPG regulation of hemoglobin helps facilitate oxygen release from red blood cells to tissues, especially when tissues need oxygen more (e.g., during exercise or in low-oxygen environments).
• This shunt provides a way for RBCs to alter glycolysis specifically for oxygen regulation, rather than for energy production alone.
Great question! The 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells (RBCs) plays a critical role in regulating oxygen release from hemoglobin. Here’s how it works:
Hemoglobin’s Oxygen Binding and Release:
• Hemoglobin is a protein in RBCs that binds oxygen in the lungs and releases it in tissues.
• Hemoglobin binds oxygen in a cooperative manner: when one oxygen molecule binds, it makes it easier for subsequent oxygen molecules to bind. The reverse is also true: when one oxygen molecule is released, it makes it easier for others to be released.
• Hemoglobin undergoes a conformational change between two states:
• R-state (relaxed state): High affinity for oxygen (binds oxygen tightly).
• T-state (tense state): Low affinity for oxygen (releases oxygen easily).
How 2,3-BPG Affects Hemoglobin:
• 2,3-BPG binds to the T-state (the low-affinity, deoxygenated form) of hemoglobin.
• When 2,3-BPG binds, it stabilizes the T-state and lowers the affinity of hemoglobin for oxygen.
• This means that hemoglobin will more easily release oxygen to the tissues where it is needed.
Why does this happen?
• T-state hemoglobin is the form that is ready to release oxygen. The binding of 2,3-BPG to hemoglobin helps to hold it in the T-state, preventing hemoglobin from grabbing onto oxygen too tightly.
• When 2,3-BPG binds, it creates a stronger interaction between hemoglobin subunits that prevents oxygen from binding too tightly. This pushes the equilibrium toward oxygen release rather than binding.
Effect in Tissues:
• In tissues, where oxygen levels are lower (because the tissues are using oxygen for metabolism), 2,3-BPG helps ensure that hemoglobin releases more oxygen.
• This is especially important when oxygen demand is high (e.g., during exercise, in high-altitude conditions, or in rapidly metabolizing tissues).
Summary:
• 2,3-BPG binds to the T-state of hemoglobin, lowering its affinity for oxygen, which promotes oxygen release in tissues.
• The presence of 2,3-BPG makes it easier for hemoglobin to unload oxygen when tissues need it most.
This mechanism allows red blood cells to be more efficient at delivering oxygen to tissues, particularly when those tissues are actively consuming oxygen.
Explain the Cori cycle
So you’ll feel pain after exercising cuz your body isn’t able to remove the lactate faster than it’s produced
Thanks for pointing that out! Let’s go in-depth on the Cori cycle, and then I’ll explain the confusion with transamination, alanine, and how that relates to the glucose-alanine cycle (which is a different but related concept). Let’s break it all down clearly:
Cori Cycle (Lactate Cycle)
What is it?
The Cori cycle is a metabolic pathway that allows lactate produced by anaerobic glycolysis in muscles to be converted back to glucose in the liver.
Why does it happen?
When muscles are active (e.g., during exercise), they may run low on oxygen, so they switch to anaerobic glycolysis to make ATP quickly. This produces lactate.
Too much lactate = acidosis, so it needs to be cleared. That’s where the liver comes in.
Steps of the Cori Cycle:
In the muscle:
1. Glucose → Pyruvate → Lactate (via anaerobic glycolysis)
• This makes 2 ATP per glucose, even without oxygen.
• Lactate is released into the blood.
In the liver:
2. Lactate → Pyruvate → Glucose (via gluconeogenesis)
• The liver uses ATP to do this (it’s energy expensive).
• Glucose is released back into the blood.
Back to the muscle:
3. Muscle uses that glucose again for energy.
• It becomes a cycle during prolonged anaerobic activity.
Why is the Cori cycle important?
• Prevents lactic acidosis by removing lactate from the muscle.
• Recycles carbon skeletons back into glucose.
• Helps maintain blood glucose during stress or exercise.
Don’t confuse it with the Glucose-Alanine Cycle
This is a different cycle that involves transamination and alanine, and it happens when muscles break down amino acids for energy, especially during starvation or prolonged exercise.
Glucose-Alanine Cycle:
In the muscle:
1. Pyruvate (from glycolysis) gets converted to alanine via transamination (taking an amino group from glutamate).
2. Alanine is sent to the liver.
In the liver:
3. Alanine → Pyruvate (transamination again), and the amino group goes to the urea cycle → forms urea.
4. Pyruvate → Glucose (via gluconeogenesis).
5. Glucose is sent back to the muscle.
So in summary:
Cycle Main Purpose Muscle Product Liver Substrate Liver Product
Cori Cycle Clear lactate & make glucose Lactate Lactate → Pyruvate Glucose
Glucose-Alanine Cycle Remove nitrogen & supply glucose Alanine Alanine → Pyruvate + Urea Glucose
Let me know if you want me to draw this out as a visual pathway, or if you’d like a mnemonic to remember the difference!
Explain gluconeogenesis
It uses 4ATP, 2GTP and 2NADH to produce one molecule of glucose
Almost correct — but not fully!
Gluconeogenesis actually has three main bypass steps to go around the irreversible steps of glycolysis.
Here they are:
- Pyruvate → Oxaloacetate → Phosphoenolpyruvate (PEP)
• Bypasses the irreversible pyruvate kinase step of glycolysis.
• Enzymes:
• Pyruvate carboxylase (needs Biotin, B7)
• PEP carboxykinase (PEPCK) - Fructose-1,6-bisphosphate → Fructose-6-phosphate
• Bypasses phosphofructokinase-1 (PFK-1) of glycolysis.
• Enzyme:
• Fructose-1,6-bisphosphatase - Glucose-6-phosphate → Glucose
• Bypasses hexokinase/glucokinase of glycolysis.
• Enzyme:
• Glucose-6-phosphatase
So in simple terms:
Gluconeogenesis has 3 bypass steps, not just 2!
Would you like a visual flow (like 5-second drawing style) to help you never forget these?
I can do that if you want!
Step 1: Pyruvate → Oxaloacetate (OAA)
Enzyme: Pyruvate carboxylase
Why this happens:
• The pyruvate kinase step in glycolysis is irreversible, so the body needs a new path to get from pyruvate back to PEP.
• Instead of reversing that step directly, it forms oxaloacetate (OAA) as an intermediate.
How it works:
• Pyruvate carboxylase adds a CO₂ (carboxyl group) to pyruvate.
• It uses biotin as a cofactor (biotin carries CO₂).
• It also uses ATP to power the reaction.
Result:
You now have a 4-carbon compound (OAA) from a 3-carbon pyruvate.
You made 2 pyruvate so in your conversion to 2 oxaloacetate, you use 2 ATp here
Step 2: Oxaloacetate → Phosphoenolpyruvate (PEP)
Enzyme: PEP carboxykinase (PEPCK)
Why this happens:
• Now that we have OAA, we can remove the extra carbon (CO₂) and attach a phosphate to make PEP — which is the form that enters the rest of gluconeogenesis.
How it works:
• PEPCK removes a CO₂ from OAA and adds a phosphate from GTP (not ATP).
• The result is PEP, which is high-energy (like in glycolysis).
You use 2 GTp here
Steps 3–7: PEP → Fructose-1,6-bisphosphate
These are reversible steps from glycolysis.
Enzymes: Enolase, phosphoglycerate mutase, phosphoglycerate kinase (in reverse), etc.
Why this happens:
• These steps are naturally reversible, so they don’t need new enzymes.
How they work:
• The enzymes catalyze reactions based on substrate concentration.
• Since there’s more PEP, it flows toward F-1,6-bisphosphate.
Step 8: Fructose-1,6-bisphosphate → Fructose-6-phosphate
Enzyme: Fructose-1,6-bisphosphatase
Why this happens:
• In glycolysis, PFK-1 adds a second phosphate to F6P. That step is irreversible.
• So gluconeogenesis removes the phosphate instead — a different reaction.
How it works:
• The enzyme simply removes a phosphate at position 1.
• It doesn’t use ATP; it just breaks the bond and releases inorganic phosphate (Pi).
Regulation note:
This step is highly regulated because it’s a major control point — it’s like the gate that says “Do we go toward glucose or not?”
Step 9: Fructose-6-phosphate → Glucose-6-phosphate
Enzyme: Phosphoglucose isomerase
Why this happens:
• This is the reverse of the glycolysis step and is easily reversible.
How it works:
• The enzyme reshuffles the atoms to convert the 6-carbon sugar from a ketose form (F6P) to an aldose form (G6P).
Step 10: Glucose-6-phosphate → Glucose
Enzyme: Glucose-6-phosphatase
Why this happens:
• In glycolysis, the first step is phosphorylation of glucose (hexokinase/glucokinase).
• That step is irreversible, so gluconeogenesis must use a different way to get back to free glucose.
How it works:
• This enzyme removes the phosphate from G6P, releasing free glucose.
• This only happens in the liver (and kidney), because muscle lacks this enzyme — that’s why muscle keeps glucose as G6P for its own use.
Why Gluconeogenesis Works This Way (Summary):
1. Bypasses irreversible glycolysis steps by using different enzymes.
2. Uses energy (ATP, GTP) to drive reactions that wouldn’t happen otherwise.
3. Controls are tight, ensuring glucose is made only when needed.
-3-phosphate (G3P)
Enzyme: Glyceraldehyde-3-phosphate dehydrogenase
Energy Used: 2 NADH (1 per G3P formed)
• 2 1,3-BPG + 2 NADH → 2 G3P
Step 8: 3-Phosphoglycerate → 1,3-Bisphosphoglycerate
Enzyme: Phosphoglycerate kinase (reverse of glycolysis)
Energy Used: 2 ATP (1 per molecule)
• 2 3PG + 2 ATP → 2 1,3-BPG
SEQUENCIAL REACTIONS OF GLUCONEOGENESIS
Pyruvate + CO; + ATP - oxaloacetate + ADP + Pi
Oxaloacetate + GIP = phosphoenolpyruvate + CO2 + GDP
Phosphoeno|pyruvate + H,0 = 2-phosphoglycerate
2-Phosphoglycerate = 3-phosphoglycerate
3-Phosphoglycerate + ATP = 1,3-bisphosphoglycerate + ADP
1,3-Bisphosphoglycerate + NADH + H* = glyceraldehyde 3-phosphate + NAD* + Pi
Clyceraldehyde 3-phosphate = dihydroxycetone phosphate
Clyceraldehyde 3-phosphate + dihydroxyactone phosphate = fructose 1,6-bisphosphate
Fructose 1, 6-bisphosphate → fructose 6-phosphate + Pi
Fructose 6-phosphate = glucose 6-phosphate
Glucose 6-phosphate + h20 → glucose + Pi
Sum: 2 Pyruvate + 4ATP + 2GTP + 2NADH + 2H*
+ 4H2O
→ glucose + 4ADP + 2GDP + 6Phisphate , + 2NAD+
You’re very, very close — let’s just clean it up a little so it’s completely clear:
- Vitamin B1 (Thiamine)
• Used for:
Decarboxylation + Dehydrogenation together (Oxidative decarboxylation) but mainly decarboxylation
• Examples:
• Pyruvate dehydrogenase (pyruvate → acetyl-CoA)
• Alpha-ketoglutarate dehydrogenase (TCA cycle)
• Branched-chain ketoacid dehydrogenase (BCAA metabolism)
• Transketolase (HMP shunt, but no decarboxylation there) - Vitamin B2 (Riboflavin)
• Used for:
Classic dehydrogenase reactions.
• It forms FAD/FADH₂ which carries electrons.
• Examples:
• Succinate dehydrogenase (TCA cycle)
• Acyl-CoA dehydrogenase (beta-oxidation) - Vitamin B3 (Niacin)
• Used for:
Classic dehydrogenase reactions.
• It forms NAD⁺/NADH (or NADP⁺/NADPH) to carry electrons.
• Examples:
• Malate dehydrogenase (TCA cycle)
• Lactate dehydrogenase - Vitamin B7 (Biotin)
• Used for:
Carboxylation reactions (adding CO₂).
• Examples:
• Pyruvate carboxylase (gluconeogenesis)
• Acetyl-CoA carboxylase (fatty acid synthesis)
So clean clean clean summary:
Vitamin Major Role
B1 (Thiamine) Oxidative decarboxylation (remove CO₂ + move electrons)
B2 (Riboflavin) Electron transfer (dehydrogenase using FAD)
B3 (Niacin) Electron transfer (dehydrogenase using NAD)
B7 (Biotin) Carboxylation (add CO₂)
One way to memorize:
• B1 → Big “1” step: remove CO₂ + move electrons
• B2 and B3 → Help move electrons (simple dehydrogenation)
• B7 → Lucky “7” adds CO₂ (carboxylation!)
Do you want me to also show you the “big 5” enzymes that use B1, grouped together for easier memory?
(It’s a shortcut most medical students use!)
Want it?
Explain the regulation of glycolysis and gluconeogeneiss
Master Regulator: Fructose-2,6-bisphosphate (F2,6-BP)
• Activates PFK-1 (glycolysis)
• Inhibits Fructose-1,6-bisphosphatase (gluconeogenesis)
• Controlled by insulin and glucagon:
• Insulin ↑ F2,6-BP → promotes glycolysis
• Glucagon ↓ F2,6-BP → promotes gluconeogenesis
Good question — let’s break it down clearly:
Fructose-2,6-bisphosphate is NOT a normal intermediate of glycolysis or gluconeogenesis.
It is a special molecule made only for regulation — to control whether the cell does glycolysis or gluconeogenesis.
Where does it come from?
• It is made from fructose-6-phosphate (an actual glycolysis intermediate).
• An enzyme called PFK-2 (phosphofructokinase-2) converts fructose-6-phosphate into fructose-2,6-bisphosphate.
• Another enzyme activity (the F-2,6-bisphosphatase part) can break it back down.
(Important: PFK-2 and F-2,6-bisphosphatase are two activities of the same enzyme, just switched on/off by phosphorylation!)
Why is it important?
• Fructose-2,6-bisphosphate strongly activates glycolysis by stimulating PFK-1 (the main rate-limiting enzyme of glycolysis).
• It inhibits gluconeogenesis by blocking fructose-1,6-bisphosphatase (the key gluconeogenesis enzyme).
Short summary:
• Fructose-6-phosphate → Fructose-2,6-bisphosphate by PFK-2 (regulatory enzyme).
• Fructose-2,6-bisphosphate then tells the cell:
• “Go glycolysis!” if food is plenty.
• “Stop gluconeogenesis!” if no need to make more glucose.
Would you also like a quick diagram showing how insulin and glucagon affect PFK-2 and thereby fructose-2,6-bisphosphate levels? It can make the whole thing click!
Want it?
Enzyme,Pathway,Activated by,Inhibited by
- Hexokinase/Glucokinase, Glycolysis, High glucose (activates glucokinase in liver), Glucose-6-phosphate (inhibits hexokinase). Fructose 6 phosphate inhibits glucokinase
2.Phosphofructokinase-1 (PFK-1),Glycolysis,AMP,Fructose-2,6-bisphosphate(activators)
Inhibitors(ATP, Citrate)
3.Pyruvate kinase, Glycolysis, Fructose-1,6-bisphosphate,inhibitors(ATP, Alanine, glucagon)
Alanine is made from pyruvate via transamination.
• If there’s a lot of alanine, it signals that the body already has enough building blocks for proteins and energy needs.
- Fructose-1,6-bisphosphatase,Gluconeogenesis,ATP, Citrate,AMP, Fructose-2,6-bisphosphate
- Pyruvate carboxylase, Gluconeogenesis,Acetyl-CoA,ADP
Why will pyruvate carboxylase be inhibited by ADP?
• Pyruvate carboxylase turns pyruvate into oxaloacetate to start gluconeogenesis (making glucose).
• Gluconeogenesis is energy expensive — it needs a lot of ATP.
• If ADP is high, it means energy is low (because ADP = ATP used up).
• The cell says: “No energy to waste, stop gluconeogenesis!”
• So ADP inhibits pyruvate carboxylase to save energy.
- PEP Carboxykinase (PEPCK),Gluconeogenesis,(not activated by anything), inhibited by ADP
ADP acts as an allosteric inhibitor in glycolysis and activator in gluconeogenesis because it reflects the cell’s energy state. Let me explain this in both contexts:
In Glycolysis:
• ADP as an Inhibitor for Phosphofructokinase-1 (PFK-1):
• PFK-1 is a key enzyme in glycolysis that converts fructose 6-phosphate into fructose 1,6-bisphosphate.
• ATP is both a substrate and an allosteric inhibitor for PFK-1. When the cell has high ATP, indicating sufficient energy, ATP binds to the allosteric site on PFK-1, reducing the enzyme’s activity.
• ADP, which is produced when ATP is used (e.g., during muscle contraction or high metabolic demand), can act as a signal of low energy.
• When ADP accumulates, it relieves the inhibition of PFK-1 by ATP, allowing the enzyme to function more efficiently and stimulate glycolysis, helping to generate more ATP.
• ADP and ATP Regulation:
• High ATP means the cell has energy, so glycolysis is slowed down.
• High ADP (which signals a lack of energy) activates glycolysis by inhibiting ATP’s negative effect on PFK-1, promoting ATP production.
In Gluconeogenesis:
• ADP as an Inhibitor of Gluconeogenesis:
• Gluconeogenesis is the process of generating glucose from non-carbohydrate precursors (like lactate or pyruvate), and it happens mainly in the liver and kidneys.
• When ADP levels are high (signaling low energy), the cell will downregulate gluconeogenesis to prevent wasting energy in a low-energy state.
• ADP inhibits the activity of key gluconeogenic enzymes (like fructose 1,6-bisphosphatase and PEPCK), thus slowing the production of glucose.
Why Does ADP Act This Way?
• Energy Monitoring: Cells need to balance energy production and consumption. High ATP signals that the cell has plenty of energy, so energy-consuming processes (like glycolysis and gluconeogenesis) need to slow down. High ADP signals low energy, so energy-producing processes (like glycolysis) should speed up, while energy-consuming processes (like gluconeogenesis) should slow down.
• Allosteric Regulation: The binding of ADP (or ATP) to enzymes like PFK-1 and fructose 1,6-bisphosphatase is a form of allosteric regulation, where the molecule binds to a site other than the active site and changes the enzyme’s shape, influencing its activity.
Summary:
• In glycolysis, ADP activates the pathway, stimulating the conversion of glucose to produce ATP (helping meet energy needs).
• In gluconeogenesis, ADP inhibits the pathway, as producing glucose from non-carbohydrate precursors requires a lot of energy, which isn’t ideal when energy is low.
This dynamic regulation helps the cell efficiently manage its energy state.
Difference between gluconeogenesis and glycogenolysis
Great question! Let’s break it down simply:
Gluconeogenesis vs Glycogenolysis
Feature Gluconeogenesis Glycogenolysis
Definition Making new glucose from non-carb sources (like lactate, amino acids, glycerol) Breaking down glycogen (stored glucose) into glucose
When it happens During prolonged fasting, starvation, or intense exercise During fasting or immediate energy need (like between meals or exercise)
Where it happens Liver (mainly), kidney (especially in prolonged fasting) Liver and skeletal muscle
Starting materials Lactate, alanine, glycerol, TCA intermediates Glycogen
End product Glucose Glucose-1-phosphate → Glucose-6-phosphate → Glucose (in liver only)
Energy usage Consumes ATP (energy expensive) No ATP needed; releases energy
Purpose Maintains blood glucose during long-term fasts Provides quick glucose, either for blood (liver) or local muscle use
Big Picture:
• Glycogenolysis is fast and short-term — like breaking open your savings jar.
• Gluconeogenesis is slow and long-term — like building cash from scratch when savings run out.
Let me know if you want a mnemonic or visual for this!
Glycogen storage diseases
Glucose storage diseases are a group of rare genetic disorders that affect the body’s ability to store and release glucose properly. These diseases often involve defects in enzymes responsible for glycogen synthesis or glycogen breakdown. Here’s a summary of some of the key diseases of glucose storage:
- Glycogen Storage Disease (GSD) Type I - von Gierke’s Disease
• Enzyme Deficiency: Glucose-6-phosphatase
• Pathophysiology: This enzyme is responsible for converting glucose-6-phosphate to glucose in the liver and kidneys. A deficiency causes the body to be unable to release glucose from glycogen stores, leading to hypoglycemia (low blood sugar), especially during fasting.
• Symptoms:
• Severe hypoglycemia, especially between meals
• Enlarged liver (hepatomegaly) due to the accumulation of glycogen
• Growth retardation
• Lactic acidosis
• Hyperlipidemia
• Kidney problems
• Treatment: Frequent feedings of glucose or cornstarch to maintain blood sugar levels. - GSD Type II - Pompe’s Disease
• Enzyme Deficiency: Lysosomal acid alpha-glucosidase (acid maltase)
• Pathophysiology: This enzyme is responsible for breaking down glycogen within lysosomes. A deficiency leads to the accumulation of glycogen in muscles and heart tissue.
• Symptoms:
• Progressive muscle weakness (including cardiac muscles)
• Enlarged heart (cardiomegaly)
• Respiratory issues due to muscle weakness
• Early-onset severe forms, sometimes leading to death in infancy
• Treatment: Enzyme replacement therapy (ERT) is available, helping to reduce glycogen accumulation. - GSD Type III - Cori Disease
• Enzyme Deficiency: Debranching enzyme
• Pathophysiology: The debranching enzyme is responsible for breaking down glycogen’s branched structure. A deficiency results in the accumulation of abnormal glycogen with short outer chains.
• Symptoms:
• Hypoglycemia during fasting
• Muscle weakness and liver enlargement
• Hepatomegaly
• Mild myopathy (muscle weakness)
• Treatment: A high-protein diet and cornstarch to maintain blood glucose levels during fasting. - GSD Type IV - Andersen’s Disease
• Enzyme Deficiency: Branching enzyme
• Pathophysiology: The branching enzyme is responsible for adding branches to the glycogen molecule. Deficiency leads to the formation of abnormally structured glycogen that is poorly soluble and difficult to break down.
• Symptoms:
• Progressive liver cirrhosis
• Liver failure
• Muscle weakness
• Early death (often in infancy or early childhood)
• Treatment: Liver transplant is the only current effective treatment. - GSD Type V - McArdle’s Disease
• Enzyme Deficiency: Muscle glycogen phosphorylase
• Pathophysiology: This enzyme is responsible for breaking down glycogen in muscle tissue to provide energy during exercise. A deficiency leads to an inability to properly metabolize glycogen during periods of exertion, causing muscle cramps and weakness.
• Symptoms:
• Exercise-induced muscle pain, cramps, and weakness
• Rhabdomyolysis (muscle breakdown) in severe cases
• No rise in blood lactate during exercise (as muscle glycogen isn’t broken down)
• Treatment: Avoidance of strenuous exercise, regular carbohydrate intake to maintain muscle energy levels, and in some cases, creatine supplementation for muscle function. - GSD Type VI - Hers’ Disease
• Enzyme Deficiency: Liver glycogen phosphorylase
• Pathophysiology: This enzyme is responsible for breaking down glycogen in the liver. A deficiency results in hepatomegaly and the inability to mobilize glycogen to maintain blood glucose during fasting.
• Symptoms:
• Hepatomegaly
• Mild hypoglycemia, especially after fasting
• Normal development in many cases
• Treatment: High-carbohydrate diet and cornstarch to maintain glucose levels. - GSD Type VII - Tarui Disease
• Enzyme Deficiency: Phosphofructokinase (PFK) in muscle and red blood cells
• Pathophysiology: PFK catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, a key step in glycolysis. A deficiency leads to a block in energy production from glycogen in muscles.
• Symptoms:
• Muscle cramps and exercise intolerance
• Hemolysis (destruction of red blood cells) leading to anemia
• Treatment: Avoidance of strenuous exercise, regular meals to maintain blood glucose levels. - GSD Type IX - Phosphorylase Kinase Deficiency
• Enzyme Deficiency: Phosphorylase kinase
• Pathophysiology: Phosphorylase kinase is involved in the activation of glycogen phosphorylase, which breaks down glycogen. A deficiency causes poor glycogen breakdown.
• Symptoms:
• Hepatomegaly
• Mild hypoglycemia
• Muscle weakness in some cases
• Treatment: A high-carbohydrate diet and cornstarch to maintain glucose levels.
Summary of Common Symptoms in Glycogen Storage Diseases:
• Hypoglycemia (low blood sugar)
• Hepatomegaly (enlarged liver)
• Muscle weakness or cramps
• Growth retardation (in severe forms)
• Cardiac issues (in some types like Pompe’s disease)
Treatment Strategies:
• Frequent feeding with glucose or cornstarch to prevent hypoglycemia.
• Enzyme replacement therapy (in some types like Pompe’s disease).
• Liver transplant (for severe forms like Andersen’s disease).
• Avoidance of strenuous exercise (in some types like McArdle’s disease).
These diseases highlight the critical role that proper glycogen storage and breakdown play in maintaining energy balance in the body. Treatment generally focuses on preventing hypoglycemia and maintaining normal metabolic function.
Summary of 3-Carbon Monosaccharides (Trioses):
1. Aldose (with an aldehyde group):
• Name: Glyceraldehyde
• Structure: CHO–CH(OH)–CH₂OH
• Exists as: D- and L- isomers (enantiomers)
2. Ketose (with a ketone group):
• Name: Dihydroxyacetone (DHA)
• Structure: HO–CH₂–CO–CH₂–OH
• Note: It does not have isomers because it’s symmetric
These are the simplest sugars involved in glycolysis.
Lowest number of carbons is a 3 carbon. We don’t have 2 carbons
You’re almost right, just a slight correction:
Corrected Explanation:
Disaccharides are formed by the condensation (not hydrolysis) of two monosaccharides, such as glucose units.
• The reaction releases a molecule of water (H₂O) — this is called a dehydration or condensation reaction.
• The two sugars are joined by a glycosidic bond.
Example:
Glucose + Glucose → Maltose + H₂O
• The bond formed is an α-1,4 glycosidic bond.
Summary:
• Disaccharide formation = condensation (dehydration)
• Disaccharide breakdown = hydrolysis (uses water to break bond)
Monosaccharides form aldoses and ketoses, disaccharides are water soluble (due to their hydroxyl groups, they dissolve well in water. ) and are sweet to taste(example is table sugar or sucrose) and classified based on the presence or absence of a free reducing group. What is a reducing sugar?
State some examples of reducing sugars and non reducing sugars as well as their effect on Benedict’s solution and fehlings solution
Functions of carbs:
Most abundant dietary source of energy
Participate in structure of of the cell membrane
Precursor of organic compounds such as DNA and RNA
Disaccharides are classified based on the presence or absence of a free reducing group.
Explanation:
• A reducing sugar has a free anomeric carbon (usually with a free –OH group on carbon 1 or 2) that can reduce other compounds (like Benedict’s or Fehling’s reagent).
• A non-reducing sugar has no free anomeric carbon, usually because it is involved in the glycosidic bond.
Classification:
Type Example Free Reducing Group(yes or no)? Test Result(Benedict’s solution)
Reducing Maltose, Lactose Yes Positive (color change)
Non-reducing Sucrose No Negative (no change)
Benedict’s solution is similar to Fehling’s and is used to test for reducing sugars.
Color Change with Benedict’s Solution:
When a reducing sugar is present and the solution is heated, the color changes from:
Blue → green → yellow → orange → brick red (depending on how much sugar is present)
Explanation:
• Benedict’s solution contains copper(II) ions (Cu²⁺) — that’s what gives it the blue color.
• A reducing sugar donates electrons to the copper, turning it into copper(I) oxide (Cu₂O), which is red-orange and forms a precipitate.
Fehling’s Test:
• Fehling’s solution is a blue solution that contains copper(II) ions (Cu²⁺).
• If a reducing sugar is present, it reduces Cu²⁺ to Cu⁺, forming a red or orange precipitate of copper(I) oxide (Cu₂O).
Maltose is alpha D glucose plus alpha D glucose
Lactose is alpha D galactose plus alpha D glucose
Sucrose is alpha d glucose plus beta D fructose
You’re right to point out the confusion, and I apologize for the unclear explanation earlier. Let me clarify the process in the context of Benedict’s solution and reducing sugars:
Key Concepts:
• Benedict’s Solution contains Cu²⁺ (copper(II) ions), which gives it a blue color.
• Reducing sugars are sugars that can donate electrons to other substances.
• The reaction involves the reduction of copper(II) ions (Cu²⁺) to copper(I) ions (Cu⁺) and the oxidation of the reducing sugar.
How the Reaction Works:
1. Reducing Sugar’s Role:
• A reducing sugar (like glucose or fructose) donates electrons (undergoes oxidation), causing Cu²⁺ (from the Benedict’s solution) to accept those electrons and be reduced to Cu⁺ (copper(I) ions).
2. Copper(I) Oxide Formation:
• The Cu⁺ ions then combine with oxygen to form copper(I) oxide (Cu₂O), which is a red-orange precipitate.
• Cu²⁺ is reduced to Cu⁺, and Cu⁺ combines with oxygen to form Cu₂O. In this case, copper(I) oxide (Cu₂O) is a result of oxidation of the sugar.
Why the Confusion?
• The reducing sugar is oxidized (it loses electrons), and as a result, the copper(II) ions (Cu²⁺) are reduced (they gain electrons).
• This is a redox reaction, where oxidation (electron loss) occurs with the sugar, and reduction (electron gain) happens with the copper(II) ions.
So:
• The sugar undergoes oxidation (loses electrons), and Cu²⁺ is reduced to Cu⁺ (gains electrons).
• The Cu⁺ reacts with oxygen to form Cu₂O, which gives the red-orange precipitate.
The anomeric carbon is the carbon atom in a sugar molecule that was part of the carbonyl group (either an aldehyde or a ketone) in the open-chain form of the sugar, but becomes a new chiral center when the sugar cyclizes into a ring structure.
Here’s how it works:
1. In an aldose (e.g., glucose), the anomeric carbon is the carbonyl carbon (C1) of the aldehyde group.
2. In a ketose (e.g., fructose), the anomeric carbon is the carbonyl carbon (C2) of the ketone group.
When the sugar cyclizes to form a ring, the anomeric carbon becomes bonded to an -OH group, and it can exist in two different configurations:
• α-anomer: The hydroxyl group on the anomeric carbon is trans (opposite side) to the CH2OH group.
• β-anomer: The hydroxyl group on the anomeric carbon is cis (same side) to the CH2OH group.
This difference in configuration leads to the formation of α and β anomers, which are important for the structure and function of carbohydrates.
You’re very close — and you’re thinking the right way! Let me explain it simply:
Hexokinase (muscle):
• Found in muscles (and most body tissues).
• Very sensitive: Even small amounts of glucose will make it work fast.
• This is because muscles always need energy quickly, even when blood sugar is low.
• Hexokinase gets “full” (saturated) quickly because it has a low Km (means high affinity for glucose).
Glucokinase (liver):
• Found mainly in the liver (and a bit in the pancreas).
• Not very sensitive: Needs high glucose levels to work well.
• This is because the liver only stores or removes glucose when there’s plenty in the blood (after eating).
• Glucokinase has a high Km (low affinity for glucose) — it doesn’t rush to work unless glucose is high.
In short:
• Muscle needs to grab glucose fast, even when little is available — that’s why it uses Hexokinase.
• Liver should store or release glucose carefully, only when blood sugar is high — that’s why it uses Glucokinase.
You really remembered the right idea!
Would you also want a one-line summary for quick memory? It can make it even easier to remember!
Another name for the Pentose Phosphate Pathway is the hexose monophosphate shunt (or HMP shunt).
Both names refer to the same pathway!
It’s the pathway where glucose is used to make NADPH and ribose sugars for nucleotide synthesis.
Stoichiometric Equation of the PPP
Before we dive in to the chemistry of the PPP, let’s write-out the stoichiometry for its most essential mode:
The reactants are glucose 6-phosphate + 2 NADP+ + H2O
The products are ribulose 5-phosphate + 2 NADPH + H2 + CO2
The HMP Shunt, also known as the Pentose Phosphate Pathway or the Phosphogluconate Pathway, is a biochemical pathway that serves as an alternative metabolic pathway for glucose.
The first phase is oxidative and irreversible. Glucose-6-phosphate (G6P) is converted via series of steps into Ribulose-5-phosphate. The most important catalytic enzyme is Glucose-6-phosphate Dehydrogenase (G6PD), which produces NADPH in the process. This is the major source of NADPH in the cell, and decreased NADPH can be seen in G6PD Deficiency.
The second phase is non-oxidative and reversible, and involves transketolase as a major enzyme. Ribulose-5-phosphate is converted into Ribose-5-phosphate, which can undergo further reactions to produce Fructose-6-phosphate and Glyceraldehyde-3-phosphate. Ribose-5-phosphate is an important precursor to PRPP in the Purineand Pyrimidine Synthesis pathways. Of note, the action of transketolase requires Vitamin B1/Thiamine as a cofactor.
Key Points
◦ Vitamin B1 (Thiamine)
◦ Active form is thiamine pyrophosphate (TPP), a cofactor for several dehydrogenases and other enzymes:
Transketolase
◦ Important in Hexose Monophosphate (HMP) Shunt
Alright — let’s go deep but clear into the HMP shunt (Pentose Phosphate Pathway), step by step:
Introduction: What is the HMP Shunt?
• It’s an alternative pathway for glucose metabolism.
• Main products: NADPH and ribose-5-phosphate.
• It occurs in the cytoplasm (same place as glycolysis).
• It has two phases:
1. Oxidative phase — irreversible
2. Non-oxidative phase — reversible
Phase 1: Oxidative Phase (Irreversible)
Purpose:
• Produce NADPH (for fatty acid synthesis, cholesterol synthesis, and protection against oxidative stress).
• Produce ribulose-5-phosphate (for nucleotide synthesis).
Step 1: Glucose-6-phosphate → 6-Phosphoglucono-δ-lactone
• Enzyme: Glucose-6-phosphate dehydrogenase (G6PD)
• Important event:
• NADP⁺ is reduced to NADPH.
• Note: This is the rate-limiting step (most regulated step).
• Activated when the cell needs NADPH.
• Inhibited by high NADPH levels (feedback inhibition).
Step 2: 6-Phosphoglucono-δ-lactone → 6-Phosphogluconate
• Enzyme: Lactonase
• Important event:
• Water is used to open the ring of lactone into a straight-chain sugar acid.
• No NADPH is produced here — it’s a preparation step for the next oxidation.
Step 3: 6-Phosphogluconate → Ribulose-5-phosphate
• Enzyme: 6-Phosphogluconate dehydrogenase
• Important event:
• Another NADP⁺ is reduced to NADPH.
• CO₂ is released (decarboxylation).
At the end of the oxidative phase, you get:
• 2 NADPH
• 1 Ribulose-5-phosphate
• 1 CO₂
Phase 2: Non-Oxidative Phase (Reversible)
Purpose:
• To shuffle carbons around depending on the cell’s needs.
• Produce ribose-5-phosphate for DNA/RNA synthesis.
• If the cell doesn’t need ribose, it converts sugars back to glycolytic intermediates (fructose-6-phosphate and glyceraldehyde-3-phosphate).
Key enzymes:
• Isomerase:
• Ribulose-5-phosphate → Ribose-5-phosphate (for nucleotides)
• Epimerase:
• Ribulose-5-phosphate → Xylulose-5-phosphate (isomer of ribose)
• Transketolase (needs Vitamin B1/Thiamine/TPP):
• Transfers 2-carbon units.
• Transaldolase:
• Transfers 3-carbon units.
Example reactions in this phase:
• Ribose-5-phosphate + Xylulose-5-phosphate → Glyceraldehyde-3-phosphate + Sedoheptulose-7-phosphate (transketolase)
• Glyceraldehyde-3-phosphate + Sedoheptulose-7-phosphate → Fructose-6-phosphate + Erythrose-4-phosphate (transaldolase)
• More reactions recycle sugars into intermediates of glycolysis or gluconeogenesis.
Why is the HMP Shunt important?
- NADPH production
• Needed for:
• Fatty acid synthesis
• Cholesterol synthesis
• Glutathione reduction (antioxidant defense) - Ribose-5-phosphate
• Needed for:
• DNA and RNA synthesis (nucleotides) - Flexible sugar management
• Converts sugars into whatever the cell needs:
glycolysis or nucleotide production.
Clinical Connection: G6PD Deficiency
• Without enough G6PD, you can’t make enough NADPH.
• No NADPH = No reduced glutathione (GSH).
• RBCs can’t fight oxidative stress → hemolysis → hemolytic anemia.
Final simple flow:
Glucose-6-phosphate → (Oxidative phase) → NADPH + Ribulose-5-phosphate
→ (Non-oxidative phase) → Ribose-5-phosphate or back to Glycolysis
Would you also want me to explain it like a story (with “characters” for glucose, NADPH, etc.)?
That usually helps it stick in your mind much more easily!
Want me to?
G6PD Deficiency is a X-linked recessive disorder that causes episodic breakdown of red blood cells.
Specifically, the disease is caused by decreased activity of glucose-6-phosphate dehydrogenaseor G6PD (see HMP/Pentose Phosphate Shunt - coming soon!), which converts glucose-6-phosphate to 6-phosphogluconate. More importantly, G6PD normally produces NADPH for the cell, and patients with G6PD have low NADPH levels intracellularly.
Decreased NADPH prevents the reduction of GSH (glutathione), which typically scavenges free radicals produced by oxidative stress. Red blood cells (RBCs) are particularly affected, and hemolysis occurs due to oxidative damage. G6PD Deficiency is a X-linked recessive disorder that causes episodic breakdown of red blood cells.
Specifically, the disease is caused by decreased activity of glucose-6-phosphate dehydrogenaseor G6PD (see HMP/Pentose Phosphate Shunt - coming soon!), which converts glucose-6-phosphate to 6-phosphogluconate. More importantly, G6PD normally produces NADPH for the cell, and patients with G6PD have low NADPH levels intracellularly.
Decreased NADPH prevents the reduction of GSH (glutathione), which typically scavenges free radicals produced by oxidative stress. Red blood cells (RBCs) are particularly affected, and hemolysis occurs due to oxidative damage.
You have summarized most of it really well!
Let me just sharpen and clean it a little so you have an even clearer, final version in your mind:
The HMP Shunt (Pentose Phosphate Pathway / Phosphogluconate Pathway)
It is an alternative pathway for glucose metabolism with two phases:
1. Oxidative Phase (Irreversible)
• Glucose-6-phosphate (G6P) is converted to ribulose-5-phosphate. • Key enzyme: Glucose-6-phosphate dehydrogenase (G6PD). • NADPH is produced (major source in the body). • NADPH is crucial for: • Fatty acid and cholesterol synthesis, • Protection against oxidative stress (via regeneration of glutathione, GSH). 2. Non-Oxidative Phase (Reversible) • Ribulose-5-phosphate is converted into: • Ribose-5-phosphate (for nucleotide synthesis), • Fructose-6-phosphate and Glyceraldehyde-3-phosphate (can re-enter glycolysis). • Key enzyme: Transketolase, which needs Vitamin B1 (Thiamine, in the form TPP) as a cofactor.
G6PD Deficiency
• X-linked recessive disorder.
• Leads to low NADPH production.
• Without NADPH, glutathione (GSH) can’t be regenerated to fight oxidative stress.
• Especially affects RBCs (no nucleus, no mitochondria, so they depend heavily on NADPH).
• Leads to hemolysis (destruction of RBCs) especially during oxidative stress (e.g., infections, fava beans, certain drugs).
Key quick points to remember:
• Vitamin B1 (Thiamine) → required for Transketolase.
• G6PD → first step enzyme → produces NADPH.
• NADPH → protects against oxidative stress and used for biosynthesis.
• RBCs depend on this pathway for survival.
You already understood about G6PD deficiency, NADPH, oxidative damage, and the importance of Vitamin B1 very well — your understanding is strong!
Would you like me to give you a one-line memory aid too, if you want to recall it even faster in exams?
Good — you’re asking all the important questions.
Let’s go even slower, step-by-step, and really break it down so that you understand it once and for all.
- First: What’s the general idea of the HMP non-oxidative phase?
• If the cell needs ribose:
→ It stops early after making ribose-5-phosphate (needed for making DNA and RNA).
• If the cell does not need ribose:
→ It rearranges the carbon atoms to make energy molecules (glycolysis intermediates like fructose-6-phosphate and glyceraldehyde-3-phosphate). - Now: Why must it be converted to xylulose?
Answer:
Ribulose-5-phosphate can be converted into two different molecules:
• Ribose-5-phosphate (normal pathway for making DNA/RNA).
• Xylulose-5-phosphate (needed for rearranging carbon atoms for energy).
Xylulose-5-phosphate is needed to start the carbon-shuffling reactions.
Without xylulose, you cannot form the molecules needed to return to glycolysis.
- What happens after forming xylulose?
Now the cell has ribose-5-phosphate and xylulose-5-phosphate.
These two molecules are both 5-carbon sugars.
Using enzymes called transketolase and transaldolase, the cell shuffles the carbon atoms between them.
- What products are made? (Important)
Here’s exactly what happens:
• First reaction (Transketolase):
• Xylulose-5-phosphate (5C) + Ribose-5-phosphate (5C)
→ Glyceraldehyde-3-phosphate (3C) + Sedoheptulose-7-phosphate (7C)
Meaning: 2 five-carbon sugars are rearranged into a 3-carbon and 7-carbon sugar.
• Second reaction (Transaldolase): • Glyceraldehyde-3-phosphate (3C) + Sedoheptulose-7-phosphate (7C) → Fructose-6-phosphate (6C) + Erythrose-4-phosphate (4C)
Meaning: You are forming a 6-carbon sugar (fructose-6-phosphate) that goes straight into glycolysis!
• Third reaction (Transketolase again): • Xylulose-5-phosphate (5C) + Erythrose-4-phosphate (4C) → Fructose-6-phosphate (6C) + Glyceraldehyde-3-phosphate (3C)
Meaning: More glycolysis intermediates!
- Where are these products going?
• Fructose-6-phosphate → enters glycolysis (to make ATP).
• Glyceraldehyde-3-phosphate → enters glycolysis (to make ATP).
→ So basically, you are saving glucose and making energy.
- Summary in one line:
If the cell doesn’t need ribose, it converts ribulose to xylulose,
then shuffles carbons using transketolase and transaldolase
to finally produce fructose-6-phosphate and glyceraldehyde-3-phosphate
that re-enter glycolysis to make energy.
SUPER SIMPLE VERSION:
Situation What Happens
Need Ribose? Stop after Ribose-5-phosphate
No Need Ribose? Convert to Xylulose → Rearrangement → Glycolysis intermediates
Would you also like me to draw it out verbally like a very simple story (Ribulose becomes Xylulose who meets Ribose to give birth to F6P and G3P etc.)?
It sometimes helps the mind picture it better!
Should I?
You’re very close — here’s the clear connection:
• Glutathione (GSH) is the molecule that neutralizes ROS (reactive oxygen species) by giving electrons to them — that’s how it “reduces” ROS and protects the cell.
• But when GSH does this, it gets oxidized itself and becomes GSSG (oxidized glutathione, two glutathiones linked together).
• NADPH is needed because it gives electrons to regenerate GSH from GSSG using the enzyme glutathione reductase.
Simple summary:
• GSH reduces ROS.
• After reducing ROS, GSH becomes GSSG (oxidized form).
• NADPH is needed to convert GSSG back into GSH so it can work again.
Without NADPH, the cell can’t recycle GSH, and ROS would build up and damage the cell — especially dangerous in red blood cells.
Would you like me to quickly show this in a very short “cycle diagram” too? It might help you visualize it faster.
Good question — let’s go slowly and break it down!
How did we start with two xylulose-5-phosphate molecules?
In the oxidative phase of the HMP shunt:
• You convert Glucose-6-phosphate into Ribulose-5-phosphate.
• Ribulose-5-phosphate can be isomerized into Ribose-5-phosphate OR epimerized into Xylulose-5-phosphate.
Key point:
• Not all Ribulose-5-phosphate becomes Ribose.
• Some become Ribose-5-phosphate.
• Some become Xylulose-5-phosphate.
More detailed:
For example:
• 3 Ribulose-5-phosphate molecules can be produced.
• These can be rearranged by two enzymes:
• Isomerase → makes Ribose-5-phosphate (5C)
• Epimerase → makes Xylulose-5-phosphate (5C)
Usually,
you get about 1 Ribose-5-phosphate and 2 Xylulose-5-phosphate.
Summary:
• 3 Ribulose-5-phosphate →
→ 1 Ribose-5-phosphate + 2 Xylulose-5-phosphate
That’s why you have 2 Xylulose-5-phosphate molecules available
for the non-oxidative phase.
Linking to the reactions you were asking about:
First transketolase:
• 1 Ribose-5-phosphate (5C) + 1 Xylulose-5-phosphate (5C) →
→ 1 Glyceraldehyde-3-phosphate (3C) + 1 Sedoheptulose-7-phosphate (7C)
Second transaldolase:
• Glyceraldehyde-3-phosphate (3C) + Sedoheptulose-7-phosphate (7C) →
→ Fructose-6-phosphate (6C) + Erythrose-4-phosphate (4C)
Third transketolase:
• Erythrose-4-phosphate (4C) + second Xylulose-5-phosphate (5C) →
→ Fructose-6-phosphate (6C) + Glyceraldehyde-3-phosphate (3C)
In very short words:
You make 2 xylulose-5-phosphates because ribulose-5-phosphate can epimerize into them.
This allows the reactions to continue and shuffle carbons efficiently.
Would you want me to also show you a small map of how 3 ribulose-5-phosphates flow through the entire non-oxidative phase, step-by-step?
(It will make the whole thing feel very easy!)
Should I?
Regulation of HMP
Good — let’s now add regulation of the HMP shunt clearly:
Regulation of the HMP Shunt (Pentose Phosphate Pathway)
Main regulator:
• Glucose-6-phosphate dehydrogenase (G6PD) — the first enzyme and rate-limiting step.
What activates (turns it ON)?
• High NADP⁺ levels
(NADP⁺ means the cell needs to make NADPH, so the pathway starts.)
• Increased need for NADPH
(example: fatty acid synthesis, antioxidant defense during oxidative stress).
• Insulin
(after eating — insulin promotes glucose storage and building, so more NADPH is needed).
What inhibits (turns it OFF)?
• High NADPH levels
(feedback inhibition — enough NADPH tells the cell to stop making more).
• Low demand for ribose-5-phosphate or NADPH
(If the cell already has enough, it slows down).
Key points:
• When NADP⁺ > NADPH, the pathway speeds up.
• When NADPH > NADP⁺, the pathway slows down.
• Insulin after meals upregulates the HMP shunt to promote anabolism (building things like fats, cholesterol).
Summary in one line:
The HMP shunt is mainly controlled by the cell’s NADPH needs and is turned on by high NADP⁺ and insulin.
Alright — let’s explain it very simply:
How insulin activates the HMP Shunt
When you eat (especially carbohydrates), blood glucose rises.
In response, insulin is released.
Insulin’s job is to promote storage and building (anabolism):
• It pushes glucose into cells.
• It tells cells to use glucose not just for energy, but also for building fats, cholesterol, nucleotides, etc.
Building these molecules needs a lot of NADPH.
(NADPH is made by the HMP shunt.)
So, insulin activates the enzyme Glucose-6-phosphate dehydrogenase (G6PD),
→ which starts the HMP shunt
→ and produces NADPH
→ helping the cell build fats, cholesterol, and detoxify free radicals.
In short:
Insulin activates HMP shunt because it pushes the cell into “building mode,” and building mode needs NADPH.
Would you also like a super short sentence to memorize this quickly too?
(Example: “Insulin → HMP → NADPH for building.”)
Want me to?
How many ATPs will be needed to produce 4 moles of pyruvate from one mole of glucose?
A. 2 B. 4 C. 6 D. 8
They say 4
Cuz one mole of glucose will give 2 of pyruvate and this gives a net of 2 ATP
So 4 pyruvate will give 4 ATp net
- When glucagon is released, each of the following is likely EXCEPT I. glycolysis will be impaired.
Il. gluconeogenesis will be impaired.
Ill. fructose 2,6-bisphosphate level will rise.
IV. fructose 6-phosphate level will rise. • a. Ill and IV.
• b. Il and IIII.
• c. I and IV.
• d. I and Il - In a biochemistry practical, milk sugar was heated with bromine water (Br2/H2O) and examined later for various properties in later stages of the experiments. The additional tests involved exploration of the various reactions of carbohydrates. Should the milk sugar be reacted with sodium borohydride, (NaBH4), under appropriate conditions, the expected products will be
A. glucaric acid and galacturonic acid. B. galacturinol and lactinol.
C. galactitol and glucitol.
D. lactitol, galactitol and glucitol.
17.Answer is b.
16.Milk sugar = lactose, made of glucose + galactose (both are aldoses).
• Bromine water (Br₂/H₂O) oxidizes aldehydes into carboxylic acids → so glucose and galactose can become acids.
• Sodium borohydride (NaBH₄) reduces carbonyl groups (C=O) into alcohols (OH).
• So when you reduce lactose, you get alditols (sugar alcohols).
From lactose:
• Glucose → Glucitol (also called sorbitol)
• Galactose → Galactitol
Thus, the correct products when lactose is reduced with NaBH₄ are galactitol and glucitol.
Immediately after removing the pectoralis major during a dissection session, a medical student observed a fascia that extended from clavicle enclosed the pectoralis
fructose
6-phosphate.
minor muscle and extended inferiorly towards the floor of the axilla. I. This fascia is pierced by the lateral pectoral nerve.
Il. This fascia forms part of the anterior wall of the axilla
Ill. The fascia encloses the subclavius muscle
• a. I, II and III.|
• b. Il and Ill only. • c. Il only.
• d. Ill only.
21.In a biochemistry practical, milk sugar was heated with bromine water (Br2/H2O) and examined later for various properties in later stages of the experiments. The additional tests involved exploration of the various reactions of carbohydrates. Should the milk sugar be reacted with sodium borohydride, (NaBH4), under appropriate conditions, the role of lactase will be similar to the role of
• a. water.
• b. bromine.
• c. heat.
• d. bromine water
Answer is A.
No problem — let me slow it down properly for you.
Here’s what’s happening:
1. You started with milk sugar (lactose). • Lactose is two sugars joined together: glucose + galactose. 2. Lactase is an enzyme that breaks lactose into glucose and galactose. 3. Bromine water reacts with simple sugars like glucose — not with the whole lactose easily. (Bromine water mainly oxidizes sugars with a free aldehyde group.) 4. So if lactase acts first, it breaks the lactose into glucose and galactose, which now can easily react with bromine water.
In simple terms:
• Lactase opens up lactose → gives free sugars.
• Bromine water reacts with the free sugars.
Both lactase and bromine water are helping to expose sugars for chemical reactions.
That’s why lactase and bromine water are doing a similar kind of job in this experiment — that’s why the answer is (d) bromine water.
Even shorter:
Substance What it does
Lactase Breaks lactose into free sugars.
Bromine water Reacts with free sugars.
Both are about making sugars ready for reaction.
Good question!
When bromine water (Br₂/H₂O) reacts with free sugars (like glucose or galactose), it oxidizes the aldehyde group (–CHO) at the top of the sugar.
The result:
• The aldehyde group (–CHO) is oxidized to a carboxylic acid group (–COOH).
• So glucose becomes gluconic acid.
• Galactose becomes galactonic acid.
In very simple terms:
Bromine water + simple sugar → sugar acid (like gluconic acid or galactonic acid).
Summary:
• Glucose + Br₂/H₂O → Gluconic acid
• Galactose + Br₂/H₂O → Galactonic acid
Would you also like a quick diagram showing how the –CHO becomes –COOH? It’s very short!
