Gluconeogenesis

Question 1

4 Steps to Get Pyruvate Back into Cytosol for Gluconeogenesis

Answer 1

1. In matrix, CO2 is activated and transferred by pyruvate carboxylase to its biotin prosthetic grouop
2. Pyruvate carboxylase then transfers the CO2 to pyruvate, generating oxaloacetate
3. Malate dehydrogenase converts oxaloacetate to malate, which can cross the mt membrane
4. In cytosol, malate reoxidized to oxaloacetate which is then decarboxylated to phosphoenolpyruvate by PEP carboxykinase, and PEP can enter gluconeogenesis

Question 2

4 Steps of Glucagon Activation of Gluconeogenesis

Answer 2

1. High glucagon causes elevated cAMP/increased PKA
2. PKA phosphorylates bifunctional PFK-2/FBP-2
3. PFK-2 is inactivated, FBP-2 is activated converting Fructose 2,6-bisPO4 to fructose 6-PO4
4. Decreased levels of fructose 2,6-bisPO4 decreases inhibition of FBP-1, causing catalysis of fructose 1,6-bisPO4 to fructose 6-PO4, leading to gluconeogenesis

Question 3

Important Point about Fructose 2,6-bisPO4 Regulatory Effects

Answer 3

Doesn’t actually stimulate phosphofructokinase-1, enzyme that turns fructose 6-PO4 into fructose 1,6-bisPO4. Instead inhibits fructose bisphosphatase-1 which catalyzes opposite rxn

Question 4

2 Inhibitors of Fructose 1,6-bisphosphatase (FBP-1)

Answer 4

AMP

Fructose 2,6-bisPO4

Question 5

Glucose 6-phosphatase (function and deficiency)

Answer 5

To get glucose back into blood for gluconeogenesis/glycogenolysis bc gluco/hexokinase is irreversible
Deficiency causes hypoglycemia during fasting, have to eat many small meals

Question 6

Cori Cycle

Answer 6

Conversion (in liver) of lactate from muscles to glucose for brain energy (or returned to muscles)

Question 7

Glycogen General Structure

Answer 7

Amylopectin: alpha 1,4 glucan linkages w/ 1,6 branching

Question 8

2 Uses of Glycogen

Answer 8

Broken down in liver for glucose for brain

Broken down in muscles for immediate exercising energy

Question 9

Phosphoglucomutase

Answer 9

Converts glucose-6-PO4 into glucose 1-PO4 for glycogenesis by going through a glucose 1,6-bisPO4

Question 10

UDP-glucose pyrophosphorylase

Answer 10

Activates glucose for glycogenolysis by converting glucose 1-PO4 to UDP-glucose

Question 11

Glycogenin (4)

Answer 11

Acts as glycogen “primer” by automatically replacing UDP on UDP-glucose w/ its tyrosine residue w/out enzyme catalysis

Question 12

Glycogen synthase

Answer 12

Catalyzes glycogen polymerization from UDP-glucose

Question 13

Branching enzyme, 4:6 transferase

Answer 13

Causes branching of glycogen by cleaving “k” glycose residue and reattaching it 4 residues earlier, alpha 1,6 polymerization

Question 14

Reason for Glycogen Branching

Answer 14

Can release many glucose residues at once instead of 1 at a time

Question 15

Glycogen Phosphorylase

Answer 15

Begins glycogenolysis by using inorganic PO4 as a nphile to hydrolyze glycogen unit into glucose 1-PO4

Question 16

Glycogenolysis Activation (in liver) (5)

Answer 16

Glucagon increases cAMP, activating PKA, which phospho-activates glycogen phosphorylase kinase (a, active form), which phospho-activates glycogen phosphorylase (a, active form), which degrades glycogen

Question 17

Glycogenolysis Inhibition (4)

Answer 17

Insulin activates protein phosphatase-1, which dephospho-inactivates glycogen phosphorylase (b, inactive form) AND dephospho-inactivates glycogen phosphorylase kinase (b, inactive form)

Question 18

Glycogenolysis Activation in Muscle (3)

Answer 18

Calcium activates phosphorylase kinase, which activates glycogen phosphorylase

Question 19

Glycogen Synthase General Regulation (2)

Answer 19

Dephospho-Activated by protein phosphatase-1 (stimulated by insulin) and phospho-inactivated by PKA (from glucagon)

Question 20

Stimulator of Glycogen Synthase (not enzyme that converts to active form)

Answer 20

Glucose 6-PO4

Question 21

3 Inhibitors of Glycogen Phosphorylase in Liver

Answer 21

Glucose, Glucose 6-PO4, and ATP

Question 22

2 Inhibitors and 1 Activator of Glycogen Phosphorylase in Muscle

Answer 22

I: Glucose 6-PO4 and ATP
A: AMP

Question 23

Von Gierke Disease (cause, effect, big point)

Answer 23

Glucose 6-phosphatase deficiency, so can’t release generated glucose from liver and need to eat small meals to avoid hypoglycemia
Negates gluconeogenesis AND glycogenolysis

Question 24

Cori Disease

Answer 24

Debranching Deficiency so can’t access glucose from reserves - hypoglycemia but can be mitigated by gluconeogenesis

Question 25

Fructose Metabolism in Liver

Answer 25

Fructokinase converts to Fructose 1-PO4, and Aldolase B cleaves to glyceraldehyde to enter glycolysis

Question 26

Fructose Metabolism in Muscles

Answer 26

Hexokinase non-preferably can convert to fructose 6-PO4 for glycolysis

Question 27

Essential Fructosuria (severity, cause & effect, symptom)

Answer 27

Less severe fructose metabolism disease Fructokinase deficiency, so hexokinase just processes it in muscles Fructose present in urine

Question 28

Hereditary Fructose Intolerance (3)

Answer 28

Very severe fructose metabolism disease ("fructose poisoning") Lack of Aldolase B leads to buildup of fructose 1-PO4 in cells until poisoning Have to avoid fructose and sucrose entire life

Question 29

Sorbitol (2)

Answer 29

From glucose metabolism to create fructose for sperm nutrition Causes swelling of cells from hyperglycemia bc draws water in

Question 30

Galactose Source

Answer 30

Lactose

Question 31

Galactokinase

Answer 31

Creates Galactose 1-PO4 from galactose

Question 32

Galactose 1-PO4 unidyltransferase

Answer 32

Causes exchange b/w Galactose 1-PO4 and UDP-glucose, creating UDP-galactose and glucose 1-PO4

Question 33

UDP-Hexose 4-epimerase

Answer 33

Isomerizes b/w UDP-galactose and UDP-glucose

Question 34

Galactokinase Deficiency vs. Classic Galactosemia (2)

Answer 34

Latter is from deficiency in galactose 1-PO4 unidyltransferase and causes poisoning more severely

Question 35

2 Purposes of PPP

Answer 35

Produce NADPH for reductive biosynthesis | Produce Ribose-5-PO4 for nucleic acid synthesis

Question 36

2 NADPH Produce Steps of PPP

Answer 36

Glucose 6-PO4 Dehydrogenase | 6-Phospho Gluconate to Ribulose 5-PO4

Question 37

Glucose 6-PO4 Dehydrogenase (3)

Answer 37

Converts glucose 6 PO4 to 6-P Gluconolactone Rate limiting enzyme of PPP First NADPH producing step of PPP

Question 38

3 Transfers from Glycolysis to PPP (and what they're for)

Answer 38

Glucose 6-PO4 for NADPH production | Fructose 6-PO4 and Glyceraldehyde 3-PO4 for riboses for nucleic acids/mitosis

Question 39

2 Reentery Points to Glycolysis from PPP

Answer 39

Fructose 6-P and Glyceraldehyde 3-P

Question 40

Transketolase

Answer 40

TPP-dependent enzyme that converts b/w all the ketoses in PPP

Question 41

Ribose 5-P

Answer 41

Product in PPP from ribulose 5-P for NA biosynthesis

Question 42

3 Free Radical Scavenger Enzymes (and actions)

Answer 42

Superoxide dismutase - converts superoxide to O2 or H2O2 Catalase - converts H2O2 to O2 or H2O Glutathione Peroxidase - converts H2O2 to H2O

Question 43

NADPH Antioxidant Action

Answer 43

Acts as reducing equivalent for glutathione reductase to reduce glutathione so glutathione peroxidase can use to convert H2O2 to H2O

Question 44

NADPH Nitric Oxide Synthesis Action

Answer 44

Acts as reducing equivalent for NO synthase to convert O2 to NO

Question 45

NADPH Detoxification Action

Answer 45

Acts as reducing agent for Cyt P450 reductase enzymes to make foreign objects more polar/soluble for excretion

Question 46

NADPH Phagocytosis Action

Answer 46

Intention makes superoxide from O2 in order to destroy phagocytized microorganisms

Question 47

NADPH Role in Hemolytic Anemia

Answer 47

When glucose 6-P dehydrogenase deficient, cell can't use it to produce NADPH and thus set off by oxidative stress, like T cells trying to produce and neutralize free radicals to fight infection