Ch. 14: CHO Metabolism II: Gluconeogenesis, Glycogen Flashcards Preview

Medical Biochemistry > Ch. 14: CHO Metabolism II: Gluconeogenesis, Glycogen > Flashcards

Flashcards in Ch. 14: CHO Metabolism II: Gluconeogenesis, Glycogen Deck (53):
1

What are the substrates for gluconeogenesis?

Lactate
Pyruvate
Glycerol (fr TG in adipose)
Glucogenic a.a.
(Propionate: ruminants)

2

Where does gluconeogensis occur? During starvation/metabolic acidosis?

85-95% in liver

Kidneys contribute up to 50%
Enterocytes not more than 5%

3

How much energy needed for 2 pyruvate ➡️ 1 glucose?

4 ATP
2 GTP
2 NADH

4

Fxns of gluconeogenesis?

1) Maintain [glucose]
2) Use lactate (glycolysis) & glycerol (fat breakdown)
3) Acid-base balance
4) a.a. balance
5) provision of biosynthetic precursors

5

Main 4 enzymes of gluconeogenesis? (Differ from glycolysis)

1) Pyruvate carboxylase
2) PEP carboxykinase
3) Fructose-1,6-bisphosphatase
4) Glucose-6-phosphatase

6

What is pyruvate carboxylase attached to? How attached?

Attached to biotin via lysine ➖charge

7

3 ways oxaloacetate can get out of mitochondria?

1) ➡️ PEP (PEP carboxykinase in MT and cytosol)
2) ➡️ Asp
3) ➡️ Malate

8

Of 2 shuttles which move oxaloacetate from MT ➡️ cytosol, which is major? Why?

Malate shuttle = major

Asp shuttle = minor (also need alpha-ketoglutarate in TCA cycle)

9

Mechanism of activation & transfer of CO2 to pyruvate?

1) from HCO3- TO biotin attached to pyruvate carboxylase
2) TO pyruvate ➡️ oxaloacetate
3) oxaloacetate reduced ➡️ malate
4) malate moves into cytosol, oxidized to oxaloacetate
5) decarboxylated to PEP

10

How is fructose 1,6 bisphosphatase regulated?

➖: AMP, fructose 2,6-bisphosphate (signaling via glucagon or epinephrine)

11

Dephosphorylation of G6P occurs where? Does not occur where?

Liver (& kidneys?)

NOT muscle!

12

4 ways gluconeogenesis is regulated?

1) glucagon
2) substrate availability
3) allosteric ➕ by acetyl CoA
4) allosteric ➖ by AMP

13

What are the glucogenic a.a.?

All except Lys & Leu (KL)

14

What a.a. are both glucogenic & ketogenic?

Trp, Ile, Phe, Thr, Tyr

15

Which a.a. is most important a.a. substrate for gluconeogenesis?

Alanine

16

Most tissues produce lactate ➡️ removed by liver & kidneys

How?

Actively convert lactate ➡️ glucose

17

How is severe hypoglycemia defined? (Measure)

Glucose levels ⬇️ 40 mg/dL (adults) or ⬇️ 30 mg/dL (neonates)

18

What is multiple carboxylase deficiency?

Genetic defect in holocarboxylase synthetase (➡️ no biotin attachment)

19

Which carboxylase need biotin to function?

Pyruvate
Acetyl CoA
Propionyl CoA
Beta-methylcrotonyl CoA

20

Effects of multiple carboxylase deficiency?

Develop. retardation
Ketoacidosis
Hair loss
Erythematous rash

21

What is Von Gierke's disease?

Genetic defect in G6Pase ➡️ G6P trapped in cell (liver)

22

Effects of Von Gierke's disease?

Enlarged liver
Hypoglycemia
Lactic acidosis
Hyperlipidemia
Hyperuricemia (purine ➡️ uric acid)

23

What is hypoglycin A?

Toxin of unripe akee fruit

24

How does Hypoglycin A causes hypoglycemia? (Mechanism)

Forms non-metabolizable esters with CoA & carnitine ➡️ ⬇️ CoA & carnitine pools ➡️ FA oxidation inhibited ➡️ gluconeogenesis inhibited (Long chain FA oxidation main source of ATP for gluconeogenesis)

25

Where is glycogen stored? Fxn of glycogen at each site?

Muscle: greater total amt
glycogen ➡️ G6P ➡️ energy

Liver: greater concentration
Glycogen ➡️ G6P ➡️ glucose ➡️ blood glucose

26

What two bonds are formed in glycogen?

Alpha 1➡️4 glycosidic bonds

Alpha 1➡️6 glycosidic bonds (branching)

27

Glycogen synthesis pathway?

G6P ➡️ G1P ➡️ UDP-glucose ➡️ glycogen

28

Glycogenolysis pathway?

Glycogen ➡️ G1P ➡️ G6P

29

Enzymes in glycogen synthesis?

1) Phosphoglucomutase (G6P ➡️ G1P)
2) UDP glucose pyrophosphorylase (G1P ➡️ UDP glucose)
3) Glycogen Synthase, branching enzyme & 4,6 transferase (UDP glucose ➡️ glycogen)

30

What does UDP-glucose attach to?

Glycogenin (via OH of tyr residue)

31

Autocatalysis (adding glucosyl units to glycogen via UDP glucose) occurs up to how many sugar residues?

7 residues ➡️ then glycogen synthase used

32

Enzymes in glycogenolysis?

Glycogen phosphorylase & debranching enzyme (Glycogen ➡️ G1P)

Phosphoglucomutase (G1P ➡️ G1,6P ➡️ G6P)

33

Glycogen-related diseases:

Type II: Pompe disease?

Lysosomal alpha 1➡️4 & 1➡️6 glucosidase deficiency

34

Pompe disease: main characteristics?

⬆️ [glycogen] in lysosomes

Massive cardiomegaly, heart failure

35

Glycogen-related diseases:

Type III: Cori/Forbes' disease (limit dextrinosis)?

4:4 transferase deficiency
1:6 glucosidase deficiency
(Absence of debranching enzyme)

36

Cori/Forbes' disease: main characteristics?

Fasting hypoglycemia

Abnormal glycogen structure

37

Glycogen-related diseases:

Type IV: Andersen's disease (amylopectinosis)?

Absence of debranching enzyme

38

Andersen's disease: main characteristics?

Abnormal glycogen (few branch pts)
Death via cardiac/liver failure (1st year of life)

39

Glycogen-related diseases:

Type V: McArdle syndrome?

Skeletal muscle glycogen phosphorylase deficiency
Myophosphorylase deficiency

40

McArdle syndrome: main characteristics?

Muscle cramping after exercise
⬆️ glycogen content in muscles
Little/no lactate after exercise

41

Glycogen-related diseases:

Type VI: Hers' disease?

Liver phosphorylase deficiency

42

Hers' disease: main characteristics?

⬆️ glycogen in liver

Hypoglycemia

43

Glycogen-related diseases:

Type VII: Tarui's disease?

PFK deficiency in muscle & erythrocytes

44

Tarui's disease: main characteristics?

Muscle cramping after exercise
⬆️ glycogen content in muscles
Little/no lactate after exercise
Hemolytic anemia

45

What regulates glycogen metabolism in muscle?

Epinephrine: ➕ lysis, ➖ synthesis

Insulin: ➖ lysis, ➕ synthesis

Ca2+: ➕ lysis

46

What regulates glycogen metabolism in the liver?

Glucagon: ➕ adenylyl cyclase & lysis, ➖ synthesis

Insulin: ➕ synthesis

Governing force = glucagon:insulin ratio

47

MoA of glycogen breakdown in muscle?

Epi ➡️ ➕AC, ⬆️ cAMP ➡️ ➕ protein kinase A ➡️ ➕ phosphorylase kinase A ➡️ ➕ phosphorylase A (glycogen phosphorylase) ➡️ glycogen breakdown

Ca2+ also ➕phosphorylase kinase A (binds to it's calmodulin)

48

MoA of inhibiting glycogen synthesis during glycogen breakdown?

Epi ➡️ ➕AC, ⬆️ cAMP ➡️ ➕ protein kinase A ➡️ ➖ glycogen synthase ➡️ inactivates glycogen synthesis

49

MoA of glycogen synthesis in muscle?

Insulin ➡️ ➕ protein phosphatase ➡️ ➕ glycogen synthase ➡️ glycogen synthesis

Glycogen synthase also ➕ by Glucose-6-P

50

Inhibitors of glycogen phosphorylase in liver? In muscle?

Liver: G6P, ATP, glucose

Muscle: G6P, ATP

51

Activators of glycogen phosphorylase in muscle?

AMP: Anoxia & ⬇️ ATP ➡️ AMP activates glycogen phosphorylase A (w/out phosphorylation)

Ca2+

52

Activator of glycogen synthase in muscle & liver?

G6P

53

Role of inhibitor-1 in regulating glycogen metabolism in muscle?

Epi ➡️ ➕AC, ⬆️ cAMP ➡️ ➕ protein kinase A ➡️ ➕ inhibitor-1P ➡️ ➖ protein phosphatase-1 ➡️ causes:

1) ⬇️ ➖ of phosphorylase kinase A & phosphorylase A
2) ⬇️ ➕ of glycogen synthase B