Carbohydrate Metabolism Flashcards Preview

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Flashcards in Carbohydrate Metabolism Deck (45):
1

GLUT1

Ubiquitous but high in RBCs and Brain, Km 1mM

2

GLUT2

Liver and Pancreas, Km 10mM

3

GLUT3

Neurons, Km 1mM

4

GLUT4

INSULIN DEPENDENT, skeletal muscle, adipose tissue, and heart, Km 5mM. Insulin signaling causes fusion of vesicles with plasma membrane and enables glucose uptake.

5

Net Yield of Glycolysis

2 ATP, 2 NADH, and 2 pyruvate

6

Irreversible Steps of Glycolysis

Hexokinase/Glucokinase, Phosphofructokinase 1, Pyruvate Kinase

7

Steps that require ATP for Glycolysis

Glucose -> Glucose-6-Phosphate
Fructose-6-Phosphate -> Fructose-1,6-bisphosphate

8

Steps that generate NADH for glycolysis

Glyceraldehyde 3-phosphate + NAD+ -> 1,3-bisphosphoglycerate + NADH X 2 via G3P dehydrogenase

9

Steps that generate ATP for Glycolysis

1,3 bisphosphoglycerate -> 3 phosphoglycerate + ATP X 2
Phosphoenolpyruvate -> Pyruvate X 2

10

Rate Limiting Enzyme of Glycolysis and explain

Phosphofructose Kinase 1, Insulin activates Protein phosphatase to dephosphorylate PFK-2. Activated PFK-2 can then convert F6P to F-2,6-BP, which can then activate PFK1 to convert F6P to F-1,6-BP.

11

Regulation of Pyruvate Kinase

Insulin activates protein phosphatases that dephosphorylates PK to activate it. Also activated by F-1,6-BP and insulin and is inhibited by ATP, Alanine, and glucagon. High glucagon and high cAMP activate protein kinase A, that phosphorylated PK to inactivate it.

12

RBCs and Glycolysis disorders

Since RBCs lack mitochondria, glycolysis is only mechanism for producing ATP. Failure of glycolysis results in ATP deficiency and leads to destruction of RBCs aka hemolytic anemia.

13

Brain and Glucose relationship

Glucose is one of the only fuel molecule that can cross blood brain barrier. During starvation, brain cells obtain glucose from liver via gluconeogenesis. The brain can also utilize ketone bodies for fuel during excessive starvation.

14

Carbohydrate metabolism in fed vs fasting state

Fed state: abundant glucose, release of insulin causes glucose uptake by hexokinase/glucokinase and prodction of glycogen and decreased gluconeogenesis. Fasting state: low glucose, release of glucagon and epinephrine. increase on gluconeogenesis and glyocogenolysis.

15

Diabetes

Characterized by hyperglycemia. Type 1: severe insulin deficiency due to loss of pancreatic beta cells from autoimmune destruction.
Type 2: insulin resistance that progresses to loss of beta cells function

16

Hemolytic Anemia

Results from premature destruction of RBCs from causes such as defects in glycolytic enzymes such as phosphoglucose isomerase, triosephosphate isomerase, and pyruvate kinase (most common).

17

GSD VII

Tarui disease, deficiency in PFK-1 results in exercise-induced muscle cramps, hemolytic anemia, etc.

18

Whole body needs of glucose daily?
Daily glucose requirement for brain?
Glucose present in bodily fluids?
Glucose readily available from glycogen?

160 g/day
120 g/day
20 g
190 g

19

Where does gluconeogenesis occur?

Liver, kidney, and small intestine

20

Irreversible steps of gluconeogenesis? Activators and inhibitors of each enzyme

Pyruvate -> OAA (Malate OAA shuttle) via pyruvate carboxylase (in mitochondria). Acetyl CoA activates and ADP inhibits.
OAA -> PEP via PEP carboxykinase. Activated by cortisol, glucagon, and thyroxine.
F-1,6,BP -> F6P via F-1,6-bisphosphatase (rate limiting step). Glucagon activates PKA, which phosphorylates PFK2 to inhibit it and stimulates FBPase2 to convert F26BP back to F6P.
Glucose 6P -> Glucose 6 phosphatase.

21

Cori Cycle

Links the lactate produced from anaerobic glycolysis in RBC and exercising muscle to gluconeogenesis in liver

22

Precursors of Gluconeogenesis, sources, and point of entry for each

Glycerol, lipid degradation, and DHAP
Propionate, degradation of odd-numbered FA, TCA cycle
Alanine, protein degradation, pyruvate
AA, protein degradation, TCA cycle intermediates

23

Disorders of Gluconeogenesis

F1,6BP deficiency developed from mutation in this enzyme. Presents in infancy or early childhood

24

GSD1a

Von Gierke Disease (autosomal recessive): Deficiency in G6P, patients exhibit marked fasting hypoglycemis, lactic acid

25

Fructose uptake is via what transporter?
Galactose/Glucose uptake via what?

GLUT 5
SGLT1

26

Fanconi-Bickel Syndrome

Inherited deficiency of GLUT2 in the liver, pancreatic beta cells, and PCT. Unable to take up glucose, fructose, and galactose.

27

Sorbitol accumulation defect

Glucose is reduced to sorbitol by aldose reductase.
Sorbitol oxidized to fructose by sorbitol dehydrogenase
Cells that lack sorbitol dehydrogenase can accumulate sorbitol, which triggers water influx and cause swelling. Manifests as retinopathy and cataracts.

28

Fructose entry points into glycolysis

Fructose can be converted to F6P and enter straight away of it can be converted to F1P and then glyceraldehyde, which can go to G3P and DHAP. High fructose corn syrup is bad because fructose can bypass PFK1

29

Galactosemia

Deficiency in glucose 1P uridyltransferase (GALT), leads to accumulation of galactitol.
Deficiency in galactokinase, can lead to cataracts in early infancy.

30

Oxidative steps of PPP

G6P -> Ribulose 5 P and creates 2 NADPH molecules. Rate limiting step is G6P dehydrogenase. G6PD deficiency can cause hemolytic anemia and NADPH is important for phagocytic cells for antioxidant power of glutathione reductase.

31

Non oxidative Phase of PPP

Generates Ribose-5P , G3P, and fructose 6P

32

Which cells require a high demand of ribose 5P?
Which cells require a high demand for NADH?

Rapidly dividing cells need ribulose 5P for RNA synthesis
Phagocytic cells require PPP due to NADPH for antioxidants.

33

Structure of glycogen

Glucose molecules linked together via a(1,4)-glycosidic bond and branch points formed via a-1,6 glycosidic bonds. Non reducing ends have free OH group at C4 and reducing ends are connected to glycogenin.

34

Where is glycogen stored?
Difference between liver and muscle glycogen?

Glycogen stored in liver, muscle, and other tissues and stored as granules.
Liver Glycogen - regulates blood glucose levels
Muscle glycogen - provides reservoir of fuel for physical activity.

35

Rate limiting step for Glycogenesis?

Glycogen synthase, which catalyzes the transfer of glucose from UDP-glucose to non-reducing end via a-1,4 glycosidic bond.

36

Branching enzyme of Glycogenesis?

When glycogen reaches around 11 residues, glucosyl (4:6) transferase reaches monomers a-1,6 bond.

37

Rate limiting step for Glycogenolysis?

Chain shortening done by glycogen phosphorylase (GP), which reduces glucose-1-P from the non-reducing ends of glycogen. Uses pyridoxal phosphate (Vitamin B6) as cofactor.

38

Debranching transfer enzyme for glycogenolysis?

transferase (4:4) activity to transfer a block of 3 of the remaining 4 glucose to the non reducing end forming an a-1,4-bond. Then it cleaves the a-1,6 bond of the single remaining glucose.

39

GSD II

Pompe disease, deficiency in enzyme a-1,6 glucosidase (acid maltase) -> won't be able to release terminal glucose and break down of glycogen would not be possible.

40

Activated forms of Glycogen synthase and Glycogen phosphorylase? Inactive form?

When both are P = GS is inactive and GP is active
When both are deP = GS is active and GP is inactive

41

Glucagon does NOT act on what?

Muscle

42

4 key proteins involved in regulation of insulin?

GLUT4, PKB, PP1, and GSK3

43

Type 2 Diabetes

reduced sensitivity to insulin
Blood glucose criteria : >126 mg/dl fasting or >199 mg/dl fed

44

Keys enzymes and second messengers affected by glucagon?

G Protein, AC and cAMP, PKA, PP1, PK

45

GSD 0
GSD II
GSD IV
GSD V
GSD VI

0 = -, glycogen synthase, glycogenesis: chain elongation
II= Pompe disease, acid maltase, lysosomal glycogenolysis: release of glucose
IV = Andersen disease, glucosyl (4:6) transferase, Glycogenesis: chain branchinh
V: McArdle disease: muscle glycogen phosphorylase, Glycogenolysis: Glc 1-p release
VI: Hers disease: liver glycogemn phosphporylase, Glycogenolysis: Glc 1-p release