Glycolysis Flashcards
What does glycolysis metabolize?
1 molecule of glucose to 2 molecules of pyruvate and generates 2 ATP
Glycolysis is an ______ process
Anaerobic
When pyruvate is completely oxidized under _____ conditions, it generates much more ATP
Aerobic
What is the most important fuel source in mammals?
Glucose
What are 2 systems in the brain that only rely on glucose for energy?
RBCs
Brain
What are the 3 sources of glucose in the diet?
Disaccharides, especially sucrose and lactose
Starch
Glycogen
What transporter takes up Glucose?
GLUTs (Glucose Transporters)
What are the 4 types of GLUTs and where is each found?
GLUT1- Brain and RBCs (High affinity)
GLUT2- Liver (Low affinity)
GLUT3- Neurons (High affinity)
GLUT4- Skeletal muscle, Heart, Adipose Tissue (Insulin dependent)- DM affects this
What is the relationship between Km and affinity of a transporter? How does this relate to the 4 GLUTs?
The higher the Km, the lower the affinity
GLUT1: Km is 1, high affinity
GLUT2: Km is 10, low affinity
GLUT3: Km is 1, high affinity
GLUT4: Km is 5, medium affinity
Where does Glycolysis occur?
In the cytoplasm of eukaryotic cells
Glycolysis is divided into 2 stages. What are they?
- Trapping of glucose and its cleavage into 2 interconvertible 3-carbon molecules
- Generation of ATP
What does the first stage of glycolysis begin with and what enzyme is used to phosphorylate it? What is the final product of stage 1 of glycolysis?
Begins with Glucose, which is phophorylated by Hexokinase
Final product is Glyceraldehyde-3-phosphate
For stage 1 of glycolysis, how many ATP are used and generated?
No ATP generated
2 ATP molecules consumed
*This is why stage 1 “traps glucose”
What are the 3 main reactions of the first step of glycolysis?
Phosphorylation
Isomerization
A second phosphorylation
What are the 5 steps of the first stage of glycolysis and the enzymes that catalyze each step?
- Glucose is converted to Glucose-6-phosphate by Hexokinase (in all tissues) and Glukokinase (in liver). *ATP is used. *Traps glucose.
- G6P is isomerized to Fructose-6-phosphate by the enzyme Phosphoglucoisomerase.
- F6P is phosphorylated to Fructose-1,6-bisphosphate by the enzyme Phosphofructokinase. *ATP is used. *Rate limiting enzyme of glycolysis.
- F-1,6BP is broken down to Glyceraldehyde-3-Phosphate and Dihydroxyacetone Phosphate by the enzyme Aldolase.
- DHAP is isomerized to G3P by the enzyme Triose Phosphate Isomerase.
What is another name for G3P used in some textbooks and in the lecture slides?
GAP
What enzyme catalyzes the rate limiting step of glycolysis?
Phosphofructokinase
What is the overall summary of the second stage of glycolysis?
Use G3P from stage 1 and convert it into 2 Pyruvate while making net 2ATP (ATP is made 4 times, but we used 2 ATP in the 1st stage)
What are the 5 steps of the 2nd stage of glycolysis and the enzymes that catalyze each step?
- GAP/G3P is oxidized to form 1,3-biphosphoglycerate by the enzyme Glyceraldehyde-3-phosphate Dehydrogenase (Forms NADH from NAD+)
- 1,3-BPG is dephosphorylated to 3-Phosphoglycerate by the enzyme Phosphoglycerate Kinase. *Makes ATP
- 3-PG moves a phosphate from 3rd to 2nd position via Phosphoglycerate Mutase to form 2-Phosphglycerate
- 2-PG is dehydated by Enolase to form Phosphoenolpyruvate (PEP). *Makes H2O
- PEP is dephosphorylated to Pyruvate via Pyruvate Kinase. *Makes ATP
**Remember that this process occurs twice, so every product and byproduct is made twice
What are the 3 fates of Pyruvate?
Converted into:
Acetaldehyde- Made in low O2 conditions. Used to form ethanol.
Lactate- Made in low O2 conditions.
Acetyl CoA- used for further oxidation via CTA
What 2 monosaccharides make up Sucrose?
Glucose and Fructose
What 2 monosaccharides make up Lactose?
Glucose and Galactose
If Galactose is found in the body and needs to be used in Glycolysis, what step will it enter glycolysis?
Stage 1, step 2- it will be converted into G6P
If Fructose is found in the body and needs to be used in Glycolysis, what step will it enter glycolysis?
Fructose (in adipose tissue) Stage 1, Step 3- it will be converted into F6P
Fructose (in liver) Stage 1, Step 4- it will be converted into DHAP
Fructose (in liver) Stage 1, Step 5- it will be converted into G3P
What is important and potentially dangerous about Fructose being present in the body?
Fructose in the liver can bypasses the regulation/rate limitin step of glycolysis and can cause liver cirrhosis
What are the 3 main regulatory enzymes of Glycolysis?
Hexokinase- Traps glucose
Phosphofructokinase- Rate limiting step
Pyruvate Kinase- Ends Glycolysis to form pyruvate
What are the regulatory steps of glycolysis important for?
Generating ATP during activity
Maintain blood glucose levels
List out each regulatory step in Glycolysis while at rest and during exercise
AT REST:
- G6P inhibits Hexokinase activity
- High ATP/AMP ratio inhibits enzymes PFK and Pyruvate Kinase
During Exercise:
- Low ATP/AMP ratio stimulates PFK activity
- F-1,6-BP (product from PFK) stimulates Pyruvate Kinase activity
Describe Glucokinases activity level when blood glucose is low
Low- it is inhibited because you do not want to trap glucose
Describe how glycolysis is related to obesity
Excess Acetyl CoA is converted into fatty acids, which can be transported to dipose tissue to form triacylglycerols
What causes Lactose inteolerance?
Deficiency in the enzyme lactase, which is used to break down glucose and galactose
What is Galactosemia and what does it cause?
Inherited deficiency of Galactose 1-phosphate uridyl transferase activity
Leads to infants inability to thrive:
- Vomiting/diarrhea after consuming milk
- Hepatosplenomegaly/jaundice/cirrhosis
- Cataracts from Galactitol deposits in the eye
- Elevation of blood galactose levels
What is the treatment for Galactosemia?
Remove galactose (and lactose) from diet
How do tumors relate to Glycolysis?
They have enhanced rates of glucose uptake and glycolysis
What is the Warbug Effect? What is it AKA?
The ability of tumors to metabolize glucose to lactate even in the presence of oxygen (this process usually occurs in low O2 conditions)
Aerobic Glycolysis
What diagnostic capabilities do we have to find tumors. Describe how it is used.
Positron Emission Tomography (PET)
Computer Aided Tomography (CAT)
A non-metabolizable analog of glucose is introduced into the blood and these scans will detect where they undergo glycolysis in the body, which shows where the tumor is located in the body.
What glucose transporter is the main transporter in the liver?
GLUT2
What enzyme is the most important regulator of glycolysis?
Phosphofructokinase
Which of the following is not an intermediate in the glycolytic pathway? A. 3-Phosphoglycerate B. Fructose 1,6- bisphosphoglycerate C. Glucose 1-phosphate D. Glyceraldehyde 3-phosphate E. Phosphoenolpyruvate
Glucose 1-phosphate