Glycolysis Practice Flashcards

A set of 400 practice flashcards covering all aspects of glycolysis based on lecture slides and notes, including enzymes, regulation, pathways, and clinical links.

What is the core function of glycolysis?

To take one six-carbon glucose and split it into two molecules of three-carbon pyruvate.

Where in the cell does glycolysis occur?

In the cytoplasm (cytosol).

Does glycolysis require oxygen to run?

No, it can run with or without oxygen.

In what domains of life is glycolysis found?

Bacteria, Archaea, and Eukaryotes (it is universal).

What is the approximate evolutionary age of the glycolytic pathway?

Roughly 3.5 billion years.

How many enzymes are involved in the standard glycolytic pathway?

Ten enzymes.

What are the two major phases of glycolysis?

The investment phase and the payoff phase.

Which steps constitute the investment phase?

Steps 1 through 5.

Which steps constitute the payoff phase?

Steps 6 through 10.

How many molecules of ATP are spent during the investment phase?

$$2 \text{ ATP}$$

How many molecules of ATP are generated during the payoff phase?

$$4 \text{ ATP}$$

What is the Net ATP yield of glycolysis per glucose molecule?

$$2 \text{ ATP net}$$

What are the three starting materials for glycolysis besides glucose?

$2 \text{ NAD}^+$, $2 \text{ ADP}$, and $2 \text{ P}_i$ (inorganic phosphate).

What is the net yield of NADH from glycolysis per glucose?

$$2 \text{ NADH}$$

How many water molecules are produced in the overall glycolysis ledger?

Two water molecules ($2 \text{ H}_2O$).

What is the starting 6-carbon sugar for the investment phase?

$$\text{Glucose}$$

What happens to glucose in Step 1?

It is phosphorylated into glucose-6-phosphate ($G6P$).

What is the enzyme for Step 1 in muscle tissue?

$$\text{Hexokinase}$$

What is the enzyme for Step 1 in liver tissue?

$$\text{Glucokinase (Hexokinase IV)}$$

Why does the cell spend ATP in the first step?

To trap glucose inside the cell and prime it for metabolism.

What is the product of Step 2?

$$\text{Fructose-6-phosphate (F6P)}$$

What enzyme catalyzes Step 2?

$$\text{Phosphoglucose isomerase}$$

What kind of chemical reaction occurs in Step 2?

Isomerization (rearrangement of an aldose to a ketose).

What is the product of Step 3?

$$\text{Fructose-1,6-bisphosphate (F-1,6-BP)}$$

Which enzyme catalyzes Step 3?

$$\text{Phosphofructokinase-1 (PFK-1)}$$

How many ATP are consumed in Step 3?

$$1 \text{ ATP}$$

What is the 'committed step' of glycolysis?

Step 3, catalyzed by $\text{PFK-1}$.

Which enzyme cleaves the six-carbon sugar into two three-carbon pieces?

$\text{Aldolase}$ (Step 4).

What are the two products of the aldolase reaction?

$\text{Dihydroxyacetone phosphate (DHAP)}$ and $\text{glyceraldehyde-3-phosphate (GAP)}$.

Which enzyme interconverts DHAP and GAP?

$$\text{Triose phosphate isomerase (TPI or TIM)}$$

How many GAP molecules effectively enter the payoff phase per glucose?

Two molecules of $\text{GAP}$.

What reaction does GAPDH catalyze in Step 6?

Simultaneous oxidation of the aldehyde and phosphorylation to form $1,3\text{-BPG}$.

What is the product of Step 6?

$$1,3\text{-bisphosphoglycerate (1,3-BPG)}$$

Where do the electrons stripped from GAP go?

They are picked up by $NAD^+$ to form $NADH$.

What type of high-energy bond is formed in $1,3\text{-BPG}$?

An acyl phosphate bond.

What is the standard free energy of hydrolysis for the phosphate on carbon-1 of $1,3\text{-BPG}$?

Roughly $-49 \, kJ/mol$.

What is the standard free energy of hydrolysis for ATP?

Roughly $-31 \, kJ/mol$.

Which enzyme produces the first ATP in the payoff phase?

$$\text{Phosphoglycerate kinase (PGK)}$$

What is the product of the PGK reaction (Step 7)?

$$3\text{-phosphoglycerate (3-PG)}$$

Describe substrate-level phosphorylation.

Making ATP directly from a high-energy substrate without a membrane or the electron transport chain.

What enzyme catalyzes Step 8?

$$\text{Phosphoglycerate mutase}$$

What occurs during the mutase reaction in Step 8?

The phosphate group moves from carbon 3 to carbon 2.

What is the product of Step 8?

$$2\text{-phosphoglycerate (2-PG)}$$

Which enzyme catalyzes the dehydration in Step 9?

$$\text{Enolase}$$

What high-energy molecule is produced in Step 9?

$$\text{Phosphoenolpyruvate (PEP)}$$

What is the standard free energy of hydrolysis for PEP?

Roughly $-62 \, kJ/mol$.

Which enzyme catalyzes the final step (Step 10)?

$$\text{Pyruvate kinase}$$

What are the products of Step 10?

$\text{Pyruvate}$ and $\text{ATP}$.

Is the pyruvate kinase reaction reversible?

No, it is irreversible under physiological conditions.

Why is Step 10 irreversible?

Because the energy released from PEP ($62 \, kJ/mol$) is twice what is needed to make ATP ($31 \, kJ/mol$); the rest is lost as heat.

Identify the three irreversible steps of glycolysis by enzyme name.

$\text{Hexokinase}$, $\text{PFK-1}$, and $\text{pyruvate kinase}$.

What regulates reversible reactions in a pathway?

Mass action (shifts in metabolite concentrations).

What regulates irreversible reactions?

Allosteric switches, covalent modifications, or hormonal control.

What is the sensitive signal for energy charge in muscle?

The ratio of $\text{ATP}$ to $\text{AMP}$.

How does ATP affect PFK-1?

It acts as an allosteric inhibitor.

How does AMP affect PFK-1?

It acts as an allosteric activator that relieves ATP inhibition.

Which has a higher affinity for the PFK-1 allosteric site in muscle: ATP or AMP?

$$\text{AMP}$$

At rest, what inhibits hexokinase in muscle?

Feedback inhibition by its product, $G6P$.

Why does G6P accumulate in a resting muscle cell?

Because $PFK\text{-}1$ is inhibited (by high ATP), slowing down the entire pathway.

What is 'feed-forward stimulation' in muscle glycolysis?

$F\text{-}1,6\text{-}BP$ (product of Step 3) activates $\text{pyruvate kinase}$ (Step 10).

What is the primary mandate of liver glycolysis?

To manage glucose for the whole body by buffering blood sugar levels.

What is the Km of hexokinase found in muscle?

Approximately $0.1 \, mM$.

What is the Km of glucokinase found in the liver?

Approximately $8 \, mM$.

What is the normal blood glucose concentration?

About $5 \, mM$.

Why is glucokinase sensitive to blood glucose changes while hexokinase is not?

Hexokinase is saturated at $5 \, mM$ (flat curve), but glucokinase is well below its Km (steep curve).

Name the hormone associated with the 'fed state'.

$$\text{Insulin}$$

Name the hormone associated with the 'fasted state'.

$$\text{Glucagon}$$

What is the major allosteric activator of liver PFK-1 that is linked to hormones?

$$\text{Fructose-2,6-bisphosphate (F-2,6-BP)}$$

Which metabolite from the TCA cycle inhibits liver PFK-1?

$$\text{Citrate}$$

What does high citrate signal to the liver?

That there is plenty of downstream fuel from the TCA cycle, so glycolysis can slow down.

What enzyme controls the levels of $F\text{-}2,6\text{-}BP$?

The bifunctional enzyme $\text{PFK-2/FBPase-2}$.

What happens when the bifunctional enzyme is dephosphorylated?

$\text{PFK-2}$ activity is on, building up $F\text{-}2,6\text{-}BP$.

What happens when the bifunctional enzyme is phosphorylated?

$\text{FBPase-2}$ activity is on, destroying $F\text{-}2,6\text{-}BP$.

How does insulin affect liver glycolysis through phosphorylation?

Insulin activates phosphatases that dephosphorylate $\text{PFK-2/FBPase-2}$, raising $F\text{-}2,6\text{-}BP$ and turning on glycolytic flux.

How does glucagon affect liver glycolysis?

It raises $cAMP$ to activate $\text{Protein Kinase A (PKA)}$, which phosphorylates $\text{PFK-2/FBPase-2}$, lowering $F\text{-}2,6\text{-}BP$ and stopping glycolysis.

Does muscle respond to glucagon?

No, muscle lacks a functional glucagon receptor.

Which hormone triggers GLUT4 translocation in muscle?

$$\text{Insulin}$$

How does epinephrine affect the liver?

It triggers the same $\text{PKA}$ pathway as glucagon to shut off liver glycolysis.

Why can't muscle pyruvate kinase be switched off by PKA-mediated phosphorylation?

The muscle isozyme lacks the regulatory serine residue found in the liver version.

Define fermentation.

The anaerobic reduction of pyruvate to regenerate $NAD^+$ for glycolysis.

What is the product of fermentation in humans?

$$\text{Lactate}$$

What are the products of fermentation in yeast?

$\text{Ethanol}$ and $CO_2$.

What is the primary purpose of lactate fermentation?

To reoxidize $NADH$ to $NAD^+$ so $\text{GAPDH}$ can keep glycolysis running.

What enzyme catalyzes the conversion of pyruvate to lactate?

$$\text{Lactate dehydrogenase (LDH)}$$

Which cells in the body ferment all their pyruvate to lactate continuously?

$$\text{Red blood cells (RBCs)}$$

Why do RBCs only run glycolysis/fermentation?

They lack mitochondria.

Which enzyme found in yeast is absent in humans?

$$\text{Pyruvate decarboxylase}$$

Which cofactor is used by both pyruvate decarboxylase and pyruvate dehydrogenase?

$$\text{Thiamine pyrophosphate (TPP)}$$

How many ATP are yielded per glucose in aerobic respiration?

Approximately $30 \text{ to } 32 \text{ ATP}$.

Where is the majority of ATP produced in aerobic respiration?

The electron transport chain (oxidative phosphorylation).

What describes the cycling of lactate between muscle and liver?

The $\text{Cori cycle}$.

How many ATP are spent by the liver to remake glucose in the Cori cycle?

$6 \text{ ATP}$ per glucose recreated.

What percentage of dietary fructose is metabolized by the liver?

Roughly $70 \%$.

What enzyme phosphorylates fructose in the liver?

$$\text{Fructokinase (or ketohexokinase)}$$

Why is hepatic fructose metabolism problematic?

It enters glycolysis as GAP/DHAP, bypassing the major $\text{PFK-1}$ regulatory checkpoint.

What disease is driven by chronically high fructose intake?

$$\text{Non-alcoholic fatty liver disease (NAFLD)}$$

What enzyme phosphorylates fructose in muscle and adipose tissue?

$$\text{Hexokinase}$$

What intermediate does galactose enter as?

$$\text{Glucose-6-phosphate (G6P)}$$

What is the name of the galactose metabolic pathway?

The $\text{Leloir pathway}$.

Which enzyme deficiency is the most common cause of classic galactosemia?

$$\text{GALT (Galactose-1-phosphate uridylyltransferase)}$$