Chapter 16: Glycolysis Flashcards
Why is glycolysis important?
Central pathway for production of:
- energy (ATP)
- carbons for biosynthetic pathways (fatty acids and amino acids)
Glucose is the most _____ hexose and has a strong tendency to exist in __________.
Stable
Ring formation
Overview: Glucose is converted into…
2 pyruvate and 2 ATP via 10 enzymatic steps
Glycolysis is present…
In all organisms and is an anaerobic process
In mammals, _____ and _____ can only use glucose as carbon and energy source.
Brain and RBCs
The brain cannot ______ and can only use _____.
Cannot store fuel
Can only use glucose
RBCs do not have ________. Only way for them to generate ATP is through ________.
Mitochondria
Glycolysis
In eukaryotic cells, glycolysis takes place in the _______.
Cytoplasm
Glycolysis consists of 2 stages:
Stage 1: traps glucose in the cell and destabilizes it (NO ATP generated and actually consumes 2 ATP/glucose)
Stage 2: oxidizes the 3-carbon compounds to pyruvate while generating ATP (ATP harvested)
What are the 3 irreversible steps of glycolysis?
- ) Glucose —> Glucose 6-phosphate by hexokinase
- ) Fructose 6-phosphate —> Fructose 1,6-biphosphate by PFK
- ) Phosphenolpyruvate —> Pyruvate by Pyruvate kinase
Stage 1, step 1 of glycolysis (enzyme, catalyst, etc.)
Glucose —> Glucose 6-phosphate by hexokinase
*Uses 1 ATP
Why is stage 1, step 1 important? 2 reasons.
Glucose 6-phosphate cannot diffuse through the membrane
and
Phosphoryl group destabilizes glucose and facilitates its further metabolism
Stage 1, step 2 of glycolysis (enzyme, catalyst, etc.)
Glucose 6-phosphate is isomerized to Fructose 6-phosphate by phosphoglucose isomerase
- Conversion of aldose to ketose
- 6 carbon ring -> 5 carbon ring
Stage 1, step 3 of glycolysis (enzyme, catalyst, etc.)
Fructose 6-phosphate is phosphorylated to Fructose 1,6-biphosphate by PFK
- Irreversible reaction
- Requires 1 ATP
What’s special about PFK?
Allosteric enzyme and key regulator for glycolysis
Catalyzes the irreversible reaction
Stage 2, step 4 of glycolysis (Enzyme, catalyst, etc.)
Fructose 1,6-biphosphate is hydrolyzed into GAP and DHAP by aldolase
In stage 2, step 4, which isomer is on the direct pathway of glycolysis and which is unusable?
GAP - direct
DHAP - unusable but readily converted so that 3-carbon fragment is not wasted
What catalyst interconverts DHAP into GAP?
Triose phosphate isomerase
Ketose –> Aldose
*Rapid, reversible reaction
Stage 2, step 5 of glycolysis (Enzyme, catalyst, etc.)
GAP –> 1,3-BPG by glyceraldehyde 3-phosphate dehydrogenase
- Redox reaction
- NO energy extracted at this point and 2 ATP have been invested
- NAD+ required
1,3-BPG is an _____________ with a ____________.
Acyl phosphate with a high phosphoryl-transfer potential
*High tendency to donate a phosphoryl group to become more stable
Stage 2, step 6: catalyst - glyceraldehyde 3-phosphate dehydrogenase has a 2-step process
1.) Exergonic - releases energy (thermodynamically favorable)
2.) Endergonic - uses energy (unfavorable)
Steps occur in succession
*Does not use ATP
Stage 2, step 7 of glycolysis (enzyme, catalyst, etc.)
1,3-BPG (higher phosphoryl potential than ATP) –> 3-phosphoglycerate + ATP by phosphoglycerate kinase
- Called substrate-level phosphorylation
- First ATP producing reaction, makes up for the 2 lost
Stage 2, step 8 of glycolysis (Enzyme, catalyst, etc.)
3-phosphoglycerate –> 2-phosphoglycerate by phosphoglycerate mutase
*Rearrangement
Stage 2, step 9 of glycolysis (enzyme, catalyst, etc.)
2 phosphoglycerate –> phosphoenolpyruvate by enolase
*Introduces a double bond
Stage 2, step 10 of glycolysis (enzyme, catalyst, etc.)
Phosphoenolpyruvate —> Pyruvate + ATP by pyruvate kinase
*Irreversible reaction
Net reaction of glycolysis
2 molecules of ATP generated in the conversion of glucose to 2 molecules of pyruvate
Deficiencies associated with glycolytic enzymes
- ) Hemolytic anemia (Destruction of RBCs - causes bleeding, lysing)
- ) Exercise-induced muscle cramps and muscle weakness - not enough energy for exercising
Erythrocytes (RBCs) lack…
Mitochondria and therefore rely on glycolysis to function
What enzymes are involved in exercise-induced muscle problems?
PFK
Aldolase
Phosphoglycerate kinase
What must be regenerated in order for glycolysis to proceed?
NAD+ - only limited amounts in the cell
*Comes from the vitamin niacin - which is essential in our diets, but we cannot make
There are 3 ways to regenerate NAD+
- ) Ethanol (No O2 present)
- ) Lactate (No O2 present)
- ) Acetyl CoA (if O2 present)
Ethanol - Alcoholic fermentation - what organisms are responsible for this process?
Yeast and other microorganisms
What are the two steps of alcoholic fermentation (ethanol)?
- ) Decarboxylation of pyruvate by pyruvate decarboxylase (1 C released as CO2)
- ) Reduction of acetaldehyde to ethanol + NADH by alcohol dehydrogenase
Pyruvate —> Acetaldehyde —> Ethanol
Lactate - Lactic acid fermentation - what’s involved?
Lactate is formed from pyruvate in many microorganisms and in muscle when oxygen is limited during exercise
Lactic Acid fermentation reaction
Pyruvate —> Lactate by lactate dehydrogenase using NADH
Which two ways of regeneration of NAD+ allow the operation of glycolysis in anaerobic conditions?
Lactate and ethanol regeneration methods
Fructose is mainly metabolized by the ________ using the __________ pathway.
Liver
Fructose 1-phosphate pathway
Fructose cannot directly enter the glycolytic pathway, therefore it enters glycolysis as…
Glyceraldehyde 3-phosphate (GAP)
METABOLISM OF FRUCTOSE: The reaction from fructose —> glyceraldehyde 3-phosphate
- Fructose —> Fructose 1-phosphate by fructokinase
- Fructose 1-phosphate —> Glyceraldehyde + Dihydroxyacetone phosphate by Fructose 1-phosphate aldolase
- Glyceraldehyde —> GAP by Triose kinase
METABOLISM OF GALACTOSE: The reaction of galactose –> glucose 6-phosphate
- Galactose —> Galactose 1-phosphate by galactokinase
- Galactose 1-phosphate —> Glucose 6-phosphate by phosphoglucomutase
Galactose is converted into __________ by the ___________ pathway.
Glucose 1-phosphate
Galactose-glucose interconversion pathway
Galactose enters glycolysis as…
Glucose 6-phosphate
Lactose-intolerance or hypolactasia is caused by…
Deficiency of the enzyme lactase - cleaves lactose into galactose and glucose
-Causes water imbalance -> diarrhea
What are the 5 major reactions in glycolysis?
- ) Phosphoryl transfer
- ) Phosphoryl shift
- ) Isomerization
- ) Dehydration
- ) Aldol cleavage
What is phosphoryl transfer?
Kinases - transfer of phosphoryl groups from ATP
What is phosphoryl shift?
Mutases - shift of a phosphoryl group
What is isomerization?
Isomerases - aldose is converted to a ketose or vice versa
What is dehydration?
Dehydrogenases - Elimination of water
What is aldol cleavage?
Aldolases - split of carbon-carbon bond
Enzymes are controlled by 3 different mechanisms (What are they and how fast are they?)
- ) Reversible allosteric control - milliseconds
- ) Regulation by reversible phosphorylation - seconds
- ) Transcriptional control - hours (more long-term; increases or decreases enzyme amounts)
What is the major controller of the glycolytic pathway?
PFK (Inhibit PFK, inhibit glycolysis)
PFK: what activates and inhibits it?
PFK activated by low levels of ATP by AMP
PFK inhibited by high levels of ATP
*Controlled differently in the liver than in the muscles
What inhibits hexokinase?
Glucose 6-phosphate
What inhibits pyruvate kinase? What stimulates it?
Pyruvate kinase inhibited by ATP and alanine
Pyruvate kinase stimulated by Fructose 1,6-biphosphate
In the LIVER, what inhibits and activates PFK?
PFK is inhibited by citrate
PFK is activated by fructose 2,6-bisphosphate
The livers main function is to…
Maintain blood glucose levels
Liver vs. Muscle/Brain
Liver - glucokinase - NOT inhibited by glucose 6-phosphate (lower affinity for glucose)
Muscle/brain - hexokinase - Inhibited by glucose 6-phosphate (higher affinity for glucose)
When glucose levels are high, glucose goes to?
Liver
When glucose supply is limited, glucose goes first to the _____ and _____.
Brain and muscle
Functions of GLUT1 and GLUT 3
- Present in nearly all mammalian cells
- Responsible for basal glucose uptake
- Transport glucose at NORMAL blood glucose levels
Function of GLUT2
- Present in the liver and pancreatic beta-cells
- Has a very high Km for glucose only after each meal
Function of GLUT4
- Transports glucose into muscle and fat cells
* Insulin-responsive glucose transporter (activated by insulin)
Function of GLUT5
- Present in SI
- Functions as a fructose transporter
Which situation do cancer cells prefer? Glycolysis or Oxygen?
Glycolysis (Will die if O2 present)
Cancer cells obtain ATP by metabolizing _______ to ______ even in the presence of ______. This process is termed the…
Glucose –> Lactate
Even in presence of O2
Termed: Warburg effect
Hypoxia-inducible transcription factor (HIF-1) increases the expression of most ________ and ________.
Glycolytic enzymes and glucose transporters GLUT1 and GLUT3
What stimulates HIF-1?
Exercise - this enhances the ability to generate ATP anaerobically
Which glycolytic enzymes catalyze reactions that consume ATP?
Hexokinase and phosphofructokinase-1
Which glycolytic enzyme converts dihydroxyacetone phosphate to glyceraldehyde 3-phosphate?
Triose phosphate isomerase
Which reaction is catalyzed by enolase?
2-phosphoglycerate → phosphoenolpyruvate
When oxygen is limiting (anaerobic conditions) during intense exercise, the skeletal muscle converts pyruvate into:
Lactate
How does insulin increase glucose uptake in skeletal and heart muscle?
It stimulates delivery of vesicles containing GLUT4 to the plasma membrane
Which glycolytic enzyme is directly inhibited by high concentrations of glucose 6-phosphate?
Hexokinase
Fructose enters the glycolytic pathway as:
Glyceraldehyde 3-phosphate
Which compounds allosterically activate phosphofructokinase-1?
AMP and fructose 2,6-bisphosphate
Which of the following enzymatic reactions is NOT carried out during glycolysis?
- Aldol Cleavage
- Dehydration
- Isomerization
- Oxidative Decarboxylation
- Phosphoryl Transfer
Oxidative Decarboxylation
The substrate for the enzyme enolase is:
2-phosphoglycerate
T or F: Glycolysis occurs in the mitochondria
False
The glycolytic enzyme _________________ is allosterically activated by high concentrations of fructose 1,6-bisphosphate.
Pyruvate kinase
Which reaction is catalyzed by triose phosphate isomerase?
Dihydroxyacetone phosphate → glyceraldehyde 3-phosphate
. During the Cori Cycle, the contracting skeletal muscle accumulates _______________, which serves as a precursor for ________________ in liver.
Lactate; gluconeogenesis
Phosphofructokinase-1 is the major control point of glycolysis and is allosterically inhibited by high levels of:
ATP
Fructose enters the glycolytic pathway after it is converted to the glycolytic intermediate:
Glyceraldehyde 3-phosphate
A defect in the enzyme phosphoglycerate kinase leads directly to accumulation of:
1,3-bisphosphoglycerate
The glycolytic enzyme _________________ is the major control point of glycolysis and is allosterically activated in liver by high levels of______________.
Phosphofructokinase; fructose 2,6-bisphosphate
T or F: Cancer cells convert glucose to acetyl CoA during hypoxia.
False
Which of these enzymes uses NAD+ as co-factor?
Glyceraldehyde 3-phosphate dehydrogenase
A powerful allosteric activator of phosphofructokinase (PFK) in liver is:
Fructose 2,6-bisphosphate
