Download Block 1 Unit #3

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Block 1 Unit #3
Dr. Manning – Gylcolysis 1 & 2
1. Where in the cell does glycolysis take place?
a. Glycolysis occurs in the cytoplasm
b. Describe the two stages of glycolysis.
i. Priming stage –
1. Endergonic (requires energy), 2ATP
2. Glucose  2 Glyceraldehyde 3 phosphate
ii. Oxidative phase
1. Exergonic, gives 4 ATP
2. 2 Glyceraldehyde 2 phosphate  2 pyruvate + 4 ATP + 2 NADH
c. Net is 2 ATP
2. Name the three-carbon products produced by: a) anaerobic glycolysis and b) aerobic glycolysis
a. Anaerobic – Lactate
b. Aerobic – Pyruvate
3. Explain why energy in the form of ATP must first be expended before glucose can be
catabolized. Indicate the steps which b) utilize ATP c) produce ATP. Name the enzymes
involved.
a. ATP needed?
i. Need to activate with Phosphate
ii. Prevents leakage
iii. Allows for regulation of the cycle
b. Where is ATP utilized
i. Glucose  Glucose 6 Phosphate
1. Catalyzed by Hexokinase or Glucokinase
ii. Fructose 6 Phosphate  Fructose 1,6 Bisphosphate
1. Phosphofructokinase
c. Where is ATP produced
i. 1,3 Bisphosphogylcerate  3-Phosphoglycerate
1. Phosphoglycerate kinase
ii. Phosphophenalpyruvate  Pyruvate
1. Pyruvate kinase
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4. Diagram the steps involved in the conversion of glucose to pyruvate
5. Name the 11 enzymes involved in glycolysis. Which enzyme catalyzes the uptake of inorganic
phosphate?
a. Hexokinase, glucokinase
b. Phosphohexose isomerase
c. Phosphofructose kinase (PFK) – Committed STEP!!!!!
d. Aldolase
e. Phosphotriose isomerase
[end of Priming Stage, start Oxidative phase]
f. Glyceraldehyde 3 phosphate dehydrogenase – key oxidative enzyme in glycolysis
g. Phosphoglycerate kinase
h. Phosphoglycerate kinase
i. Enolase
j. Pyruvte kinase
k. Lactate dehydrogenase
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6. How do hexokinase and glucokinase differ with respect to their affinity for glucose?
a. Hexokinase has an  affinity for glucose (it is in most tissues)
b. Glucokinase in liver (duringgluckose state)
7. Name the regulatory enzymes in glycolysis
a. Hexokinase, Phosphofructokinase, pyruvate kinase
8. What role does dihydroxyacetone phosphate play in a) glycolysis b) triglyceride synthesis c) in
the glycerol phosphate shuttle?
a. Glycolysis – dihydroxyacetone is converted to Glyceraldehyde 3 Phosphate
b. Triglyceride synthesis – it is converted to glycerol 3 phosphate which is a precursor for
biosynthesis of triglycerides in adipose tissues
c. Glycerol phosphate shuttle – it is reduced by NADH, provides a roll in regeneration of
NAD. Transferring hydrogens from cytoplasm to mitochondria
9. Define the substrate-level phosphorylation of ADP
a. 2 high energy intermediates that are generated during hydrolysis have more than enough
energy release for the substrate level phosphorylation of ADPATP = +7.3Kcal/mole
i. Phosphoenolpyruvate = -14.8 Kcal/mole
ii. 1,3 Bisphosphoglycerate= -11.8 Kcal/mole
10. Name the step at which NADH+H+ is produced in the formation of pyruvate from glucose
a. Glyceraldehyde 3 phosphate  1,3 Bisphosphoglycerate
11. Name the step at which NAD+ is regenerated in anaerobic glycolysis.
a. Pyruvate lactate
12. What is the primary rate controlling step in glycolysis? How is PFk regulated?
a. Fructose 6 PhosphateFructos 1,6 Bisphosphate
b. Inhibited by
i. ATP
ii. Citrate
iii.  acid (H+)
iv. Fatty acids
c. Stimulated by
i. AMP
ii. Fructose 2,6 bisphosphate
13. Explain why so much potential energy is generated in the oxidoreduction conversion of
glyceraldehydes 3 phosphate  1,3, bisphosphoglyceric acid
a. Two redox couples
i. RCHO/RCOOH = -0.55 Eoreduct
ii. NAD/NADH = -0.32 Eooxidant
b. G=-nFEo = nF-0.32-(-0.55)=-10.15Kcal/mole
14. Name the three irreversible steps in glycolysis
a. See #7
15. how many net moles of ATP are produced from a) the anaerobic glycolysis of 1 mole of
glucose and b) the complete oxidation of 1 mole of glucose via aerobic glycolysis?
a. 2 ATP
b. 30 or 32
16. How many net moles of NADH+H+ are produced in the pathway from glycose to pyruvate /
lactate in a) the presence and b) the absence of oxygen?
a. 2 NADH
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b. 0
17. Describe the roles of glycerophosphate and malate shuttle systems
a. These two shuttles transport hydrogens from the cytoplasm to the mitochondria
b. They are important for regenerating NAD which is needed for glycolysis to continue
i. Glycerol Phosphate Shuttle
1. FAD gives its H+s to CoEnzyme Q, so 1.5 ATP
ii. Malate Aspartate Shuttle
1. NAD gives its H+s to Complex I, so 2.5 ATP
18. How is ethanol produced form glucose?
a. This reaction is in yeast, and is anaerobic
b. Glucose + 2 ADP + 2Pi 2 ethanol + 2 CO2 + 2 ATP + 2 H2O
c. Reaction is just like anaerobic glycolysis except the steps subsequent to the formation of
pyruvate.
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19. How is ethanol metabolized by the liver?
NADH

NADH

CH3CH2OH NAD
CH3COOH  Acetyl CoA  Fatty Acid
 CH3CHO NAD

Ethanol
Acetaldehyde
Acetic Acid
20. How can excessive alcohol consumption lead to a depletion of NAD+? What are the
consequences of this?
a. 2 NAD+ are used to metabolize EtOH to Acetic Acid
b. NAD+ is needed for -oxidation, citric acid cycle, glycolysis, gluconeogenesis
c. Also increase NADH causes intermediates of gluconeogenesis to be diverted into alternate
pathways
i. Pyruvate  Lactate
ii. Oxaloacetate  Malate (instead of Oxaloacetate  Phosphenolpyruvate  Pyruvate)
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Pentose Phosphate Pathway (PPP) – Dr. Manning
1. State the primary functions of the PPP. In what part of the cell does it occur?
a. Functions – alternate way to metabolize Glucose; Glucose 6 phosphate will produce
i. NADPH – reducing agent
ii. Ribose 5 Phosphate
iii. Liberate CO2
iv. Additional functions
1. in non-oxidative phase can synthesize Ribose-5-phosphate from glycolytic
intermediates, Glyceraldehyde-3-P and Fructose in the reverse reaction
2. Pathway to synthesize Glucose from Ribose-5-phosphate
b. In the Cytoplasm
2. Write the series of reactions showing how ribose 5-phosphate and NADPH are produced from
glucose 6-phosphate. Name the enzymes involved.
H 2O
 Ribose-5-phosphate + 2 NADPH + CO2
2 NADP + Glucose-6-Phosphate 
3. What is the primary function of NADPH
a. Hydrogen donor (i.e. Fatty acid synthesis) in reductive biosynthesis
4. Name 6 important metabolic compounds which contain ribose
a. RNA
b. ATP,
c. GTP,
d. UTP
e. CoEnzyme A
f. NAD
g. NADP
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h. FAD
5. Explain why the PPP plays a very important role in red blood cells and adipose tissue.
a. NADPH maintains GSH in the reduced form
i. G-Glutathion (GSH) – tripeptide that protects against oxidative injury from peroxide
in the red blood cells
ii. Peroxide is toxic because it oxidizes SH groups on proteins
1. SH  S-S + SO3+
2. causes proteins to denature and precipitate
Reduced
H2O2
2GSH
NADP+
GS-SG
NADH
G-peroxidase
2H2O
oxidized
b. NADPH reverses the conversion of HbF3++ Met Fe+++ (cannot transport O2)
c. In Adipose tissue, NADPH is a donor for the reductive biosynthesis of fats
6. Become aware of the deleterious consequences of glucose 6 phosphate dehydrogenase (G6PD)
deficiency; can lead to drug-induced hemolytic anemia (will be covered in more detail in Red
Blood Cell Metabolism)
a. Oxidant drugs lead to an  in H2O2
b. HbF3++ Met Fe+++ 
c. Oxidized SH groups ’s denaturation and precipitation
d. Heinz bodies
i. Dark particles in red blood cells
ii. Precipitants that coalesce
e. Glucose 6 phosphate dehydrogenase needed for the regeneration of NADPH
f.  Glucose 6 phosphate causes not enough NADPH, which is needed to prevent oxidative
stress (as in #5)
7. Name the two intermediates of glycolysis produced by the PPP
a. Glyceraldehyde 3 phosphate
b. Fructose 6 phosphate
8. Give the series of reactions from ribulose 5-phosphate to glyceraldehydes 3 phosphate and
fructose 6-phosphate. Are these reactions reversible
a. 3 Pentoses (ribose) = 2 Fructose 6 phosphate + 1 glyceraldehyde 3 phosphate
b. Rxn’s reversible
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Ribulose
Phosphopentose
isomerase
Pentose
epimerase
Xyulose- 5P
-C2
+C2
Glyceraldhyde 3 P
(C3)
+C3
Fructose 6 P
(C6)
Transketolase
(transfer 2
carbons)
Ribose 5 phosphate
Sedoheputlose
(C7)
Transaldolase
(transfer 3
carbons)
-C3
Erythrose 4 P
(C4)
+C2
Fructose 6 P
(C6)
Xyulose 5 P
-C2
Transketolase
(transfer 2
carbons)
Glyceraldhyde 3 P
(C3)
9. How many carbons are transferred by tranketolase and transaldolase?
a. See figure
10. Name the co-enzyme which participates in the transketolase reaction
a. Thyamine Pyrophosphate (TPP)
b. Used as a diagnostic test for thiamine deficiency
11. How can ribose 5 P be converted to glucose 6 P?
a. 6 Ribose-5-P  4 Fructose-6-P + 2 Glyceraldehyde-3-P
Gluconeogenesis
5 Moles Glucose
12. How can glucose 6-P be converted entirely to CO2 and NADPH via the PPP?
a. 6 Glucose-6-P + 12 NADP+ + H2O  6 Ribose-5-P + 12 NADPH + 12 H+ + 6H2O
b. 6 Ribose-5-P  4 Fructose-6-P + 2 Glyceraldehyde-3-P
c. 4 Fructose-6-P + 2 Glyceraldehyde-3-P + H2O  5 Glucose 6-P
Summary of the reactions:
d. Glucose-6-P + 12 NADP + 2 H2O  6 CO2 + 12 NADPH + 12 H+ + P
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Interconversion of Hexoses – Dr. Manning
1. Outline the pathway by which galactose is converted to UDP-galactose.
2. Describe two possible fates of UDP-galactose. Why is galactose not essential in the diet?
a. Lactose synthetase  lactose
b. UDP Galactose  UDP Glucose by epimerization
c. Not required in diet because can be formed from UDP-glucose
3. Name the defective enzyme in inherited galactosemia. How does untreated galactosemina
cause cataracts?
a. Galactosemia
Galactose1 phosphateuridyltranferase
        UDP-Glucose  Glucose
Galactose  UDP-Galactose 
i. Conversion of Galactose to Glucose requires the formation of UDP-Galactos
ii. Absence of galactose-1-phosphate uridyl transferase
1. Causes an accumulation of toxic substances
2. One toxic substance is Galactitol
3. Galactitol formed from the reduction of Galactose by NADPH+H+
iii. Autosomal recessive
iv. Symptoms
1. Afflicted infants fail to thrive
2. Vomiting or diarrhea occurs following milk consumption
3. Enlargement of liver and jaundice common
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4. Mental retardation
5. Accumulation of Galactitol
a.
Galactol is osmotically active
b.
causes H2O to diffuse into the lens of the eye
c.
leades to cataract (opacity) formation in the lenses
v. Treatment
1. Exclusion of galactose from the diet
4. Distinguish between how fructose is metabolized in the liver and adipose tissue
Non-hepatic
metabolism
Fructosuria
Hepatic
metabolism
Heriditary
Fructose
intolerance
5. Describe the causes, consequences and treatments of essential fructose uria and hereditary
fructose intolerance
a. Hereditary Fructose Intolerence
i. Absence of phosphofructoaldolase B, an enzyme in the pathway for metabolizing
fructose in the Liver
ii. Severe disorder that can cause hepatic failure
iii. Treatment – avoid fructose in the diet
b. Fructose uria
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i. Absence of fructokinase, an enzyme in the pathway for metabolizing fructose in the
Liver
ii. Benign, leads to excretion of more fructose
6. Describe the formation of UDP-glucuronic acid from glucose 6-phoshate. How does UDPglucuronic acid participate as a detoxifying agent in the liver?
a. UDP-Glucose + 2 NAD+  UDP-glucouronic acid + 2 NADH =2H+
b. UDP-glucuronic acid is utilized in the body as a detoxifying agent by forming
Glucuronides
i. Glycosidic excretory products formed from foreign aromatic or alicyclic alcohols and
amines by the action of enzymes in the Endoplasmic Reticulum of the liver
7. Describe some of the main functions of the uronic acid pathway
a. This pathway is a source of UDPG for the synthesis of Glucose
b. Source of active glucuronate
c. Pathway for metabolism of non-phosphate sugars
d. Pathway for converting hexoses to pentoses
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e. Pathway for the biosynthesis of Vitamin C (ascorbic acid), except in primates (like us )
8. Can the uronic acid pathway in humans synthesize ascorbic acid (Vitamin C)? Why not?
a. No
b. Humans lack the enzyme L-gulonolactone oxidase