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Flashcards in Gluconeogenesis Deck (47)
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1

4 Steps to Get Pyruvate Back into Cytosol for Gluconeogenesis

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

2

4 Steps of Glucagon Activation of Gluconeogenesis

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

3

Important Point about Fructose 2,6-bisPO4 Regulatory Effects

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

4

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

AMP
Fructose 2,6-bisPO4

5

Glucose 6-phosphatase (function and deficiency)

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

6

Cori Cycle

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

7

Glycogen General Structure

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

8

2 Uses of Glycogen

Broken down in liver for glucose for brain
Broken down in muscles for immediate exercising energy

9

Phosphoglucomutase

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

10

UDP-glucose pyrophosphorylase

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

11

Glycogenin (4)

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

12

Glycogen synthase

Catalyzes glycogen polymerization from UDP-glucose

13

Branching enzyme, 4:6 transferase

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

14

Reason for Glycogen Branching

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

15

Glycogen Phosphorylase

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

16

Glycogenolysis Activation (in liver) (5)

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

17

Glycogenolysis Inhibition (4)

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

18

Glycogenolysis Activation in Muscle (3)

Calcium activates phosphorylase kinase, which activates glycogen phosphorylase

19

Glycogen Synthase General Regulation (2)

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

20

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

Glucose 6-PO4

21

3 Inhibitors of Glycogen Phosphorylase in Liver

Glucose, Glucose 6-PO4, and ATP

22

2 Inhibitors and 1 Activator of Glycogen Phosphorylase in Muscle

I: Glucose 6-PO4 and ATP
A: AMP

23

Von Gierke Disease (cause, effect, big point)

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

24

Cori Disease

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

25

Fructose Metabolism in Liver

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

26

Fructose Metabolism in Muscles

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

27

Essential Fructosuria (severity, cause & effect, symptom)

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

28

Hereditary Fructose Intolerance (3)

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

29

Sorbitol (2)

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

30

Galactose Source

Lactose

31

Galactokinase

Creates Galactose 1-PO4 from galactose

32

Galactose 1-PO4 unidyltransferase

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

33

UDP-Hexose 4-epimerase

Isomerizes b/w UDP-galactose and UDP-glucose

34

Galactokinase Deficiency vs. Classic Galactosemia (2)

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

35

2 Purposes of PPP

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

36

2 NADPH Produce Steps of PPP

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

37

Glucose 6-PO4 Dehydrogenase (3)

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

38

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

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

39

2 Reentery Points to Glycolysis from PPP

Fructose 6-P and Glyceraldehyde 3-P

40

Transketolase

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

41

Ribose 5-P

Product in PPP from ribulose 5-P for NA biosynthesis

42

3 Free Radical Scavenger Enzymes (and actions)

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

43

NADPH Antioxidant Action

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

44

NADPH Nitric Oxide Synthesis Action

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

45

NADPH Detoxification Action

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

46

NADPH Phagocytosis Action

Intention makes superoxide from O2 in order to destroy phagocytized microorganisms

47

NADPH Role in Hemolytic Anemia

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