Lecture 20, Glycolysis (Zaidi) Flashcards
What does glycolysis involve?
Sequence of reactions that metabolize 1 molecule of glucose to 2 molecules of pyruvate (also generates 2 ATP)
T or F: Glycolysis is aerobic.
False. Glycolysis is anaerobic.
What does glycolysis being an anaerobic process mean?
Does not use O2
Pyruvate is completely oxidized under what kind of conditions?
Aerobic
Is glycolysis or the oxidation of pyruvate more efficient?
Complete oxidation of pyruvate is more energy efficient
Why is glucose an important fuel?
Only fuel that the brain uses under conditions of non-starvation; Only fuel that red blood cells can use
Which molecules can be salvaged and resynthesized to glucose via gluconeogenesis?
Pyruvate and lactate
List sources of glucose in the diet.
Disaccharides (especially sucrose and lactose), starch, glycogen
What are glucose transporters (GLUTs)?
Glucose uptake occurs via these protein transporters
Where is GLUT1 found?
Ubiquitous but expressed highly in brain and RBCs
Where is GLUT2 found?
Main transporter in liver
Where is GLUT3 found?
Main transporter in neurons
Where is GLUT4 found?
Present in skeletal muscle, heart, adipose tissue
Describe the affinity of GLUT1.
High
Describe the affinity of GLUT2.
Low
Describe the affinity of GLUT3.
High
Which GLUT is regulated?
GLUT4
What is GLUT4 regulated by?
Insulin
Where does glycolysis occur?
In cytoplasm of eukaryotic cells
What are the 2 stages glycolysis is divided into?
- Trapping of glucose and its cleavage into 2 interconvertible 3-C molecules
- Generation of ATP
What is the overview of stage 1 of glycolysis?
Begins with phosphorylation of glucose by hexokinase and ends with isomerization of dihydroxyacetone phosphate to glyceraldehyde 3-P
How many steps are involved in stage 1 of glycolysis?
5
In the trapping of glucose and preparation phase, describe how many ATP are generated and consumed.
Generated = none Consumed = 2
What are the 3 reactions of stage 1 of glycolysis?
Phosphorylation, isomerization, second phosphorylation
What is step 1 of glycolysis?
Glucose phosphorylated to G6P by hexokinase (tissues) and glucokinase (liver). ATP is consumed.
What is step 2 of glycolysis?
G6P isomerized to F6P by phosphoglucoisomerase.
What is step 3 of glycolysis?
F6P phosphorylated to F-1,6-BP by phosphofructokinase. ATP is consumed.
What is the rate-limiting step of glycolysis?
Phosphofructokinase (step 3)
What is step 4 of glycolysis?
F-1,6-BP is broken down to G3P and DHAP by aldolase.
What is step 5 of glycolysis?
DHAP is isomerized to G3P by triose phosphate isomerase.
What is an overview of stage 2 of glycolysis?
Energy harnessed in GAP used to form ATP.
Describe the GAPDH step of glycolysis.
Oxidative phosphorylation of GAP to form 1,3-BPG; NAD+ reduced to NADH
T or F: 1,3-BPG has a low phosphoryl-transfer potential.
False. 1,3-BPG has a high phosphoryl-transfer potential.
What does NADH contain? What happens to them?
Pair of high energy electrons; Sent to ETC and plays a role in oxphos
What is an important detail about stage 2 of glycolysis?
Everything is 2x
Describe the phosphoglycerate kinase step of glycolysis.
Phosphoglycerate kinase converts 1,3-BPG to 3-PG. ADP is phosphorylated to ATP (via substrate transfer)
Describe the phosphoglycerate mutase step of glycolysis.
Phosphoglycerate mutase moves phosphate from position 3 to position 2 to form 2-PG
Describe the enolase step of glycolysis.
Dehydration of 2-PG by enolase forms PEP
What is PEP?
Enol with high phosphoryl-transfer potential
Describe the stability of PEP.
Unstable
Describe the pyruvate kinase step of glycolysis.
Pyruvate kinase transfers phosphoryl group from PEP to ADP, forming ATP. PEP is converted to pyruvate.
Describe the stability of pyruvate.
Stable ketone
T or F: The pyruvate kinase step of glycolysis is irreversible.
True.
What are the various fates of pyruvate?
- Can be reduced to lactate, with the regeneration of NAD+
- Can be oxidized aerobically via the CAC after first undergoing an oxidative decarboxylation to form acetyl CoA
- Some organisms can convert pyruvate to ethanol (maintain redox balance)
What is sucrose a disaccharide of?
Glucose and fructose
What is lactose a disaccharide of?
Glucose and galactose
What are fructose and galactose converted into?
Glycolytic intermediates
What is fructose turned into in times of high energy?
Fat
Outline fructose metabolism.
Fructose (fructokinase, ATP → ADP) → fructose 1-phosphate (fructose 1-phosphate aldolase) → ← glyceraldehyde (triose kinase, ATP → ADP) + DHAP → G3P
List the major regulatory enzymes of glycolysis.
Hexokinase, phosphofructokinase, pyruvate kinase
What is the goal of the regulation of glycolysis in muscle?
Generate ATP during activity
What regulates glycolysis in muscle?
ATP levels
What is the goal of regulation of glycolysis in the liver?
Maintain blood glucose levels
What does the regulation of glycolysis in the liver provide?
Building blocks for other pathways (in response to biochemical diversity and need)
For glycolysis in the liver, what is phosphofructokinase activated and inhibited by?
Activated by = F-2,6 BP
Inhibited by = citrate
T or F: During glycolysis in the liver, hexokinase is not inhibited by G6P.
False. There is no hexokinase in the liver. Glucokinase is the enzyme used in the liver and is not inhibited by glucose 6-phosphate.
Why is glucokinase not inhibited by G6P?
Glucose is permanently trapped
Regarding glycolysis in the liver, what is pyruvate kinase regulated by?
Allosteric effectors and covalent modification
Excessive consumption of ___ can lead to pathological conditions.
Fructose
Fructose is a component of sucrose and what?
High fructose corn syrup
Epidemiological/clinical studies have linked excessive fructose consumption to what?
Fatty liver, insulin insensitivity, obesity, T2D
T or F: The disorders associated with fructose consumption are due to the high consumption of the fructose.
False. The disorders associated with fructose consumption are due to how fructose is processed by the liver.
How is fructose processed by the liver, possibly resulting in a disorder?
- Actions of fructokinase and triose kinase bypass the phosphofructokinase-catalyzed reaction
- G3P and DHAP are processed by glycolysis to pyruvate and acetyl CoA in an unregulated fashion
- Excess acetyl CoA is converted to fatty acids, which can be transported to adipose tissue to form triacylglycerols
- Liver begins to accumulate fatty acids
The activities of which enzymes can deplete the liver of ATP and inorganic phosphate, thus compromising the liver.
Fructokinase and triose kinase
What is lactose intolerance?
Inability to metabolize lactose
What is lactose intolerance caused by?
Deficiency in lactase enzyme, which breaks down lactose to glucose and galactose
What is the disruption of galactose metabolism called?
Galactosemia
Classic galactosemia is an inherited deficiency in which enzyme?
Galactose 1-phosphate uridyl transferase
What are the symptoms of galactosemia?
Vomiting/diarrhea after consuming milk, enlargement of liver, jaundice, cataracts, lethargy and retarded mental development, significant elevation of blood-galactose levels, presence of galactose in urine
What is the diagnostic criterion of galactosemia?
Absence of transferase in RBC
What is the treatment for galactosemia?
Remove galactose (and lactose) from diet
Is the removal of galactose and lactose a total cure/treatment for galactosemia?
No. Elimination of galactose from the diet prevents liver disease and cataract development, but the majority of patients still suffer from central nervous system malfunction. Most commonly, a delayed acquisition of language skills.
T or F: Infants afflicted with galactosemia fail to thrive.
True.
What is a cataract?
Clouding of the normally-clear lens of the eye
What is the pathology of a cataract?
If the tranferase is not active in the lens of the eye, the presence of aldose reductase causes the accumulating galactose to be reduced to galactitol.
Describe the rates of glucose uptake and glycolysis in tumors.
Enhanced
Describe aerobic glycolysis, or the Warburg effect.
Rapidly growing tumor cells metabolize glucose to lactate even in the presence of oxygen.
T or F: Tumors with high glucose uptake are particularly aggressive.
True.
How can a tumor be visualized/treatment efficacy be determined?
2-18F-2D-deoxyglucose can be detected by a combination of PET (positron emission tomography) and CAT (computer-aided tomography) scans
