Biochem Block 4 - Week 1

Front 1

Which GLUT transporter is found in almost all tissues and provides basal glucose uptake?

Back 1

GLUT1

Front 2

Which GLUT transporter is found in liver, pancreatic cells, and the basolateral membrane of small intestines?

Back 2

GLUT2

Front 3

Which GLUT transporter removes excess glucose from the blood and plays a role in insulin secretion?

Back 3

GLUT2

Front 4

Which GLUT transporter is found in muscle and fat cells?

Back 4

GLUT4

Front 5

Which GLUT transporter is found in the mucosal membrane of the small intestine and spermatozoa?

Back 5

GLUT5

Front 6

Which GLUT transporter acts as a fructose transporter?

Back 6

GLUT5

Front 7

Which GLUT transporter is insulin sensitive?

Back 7

GLUT4

Front 8

What are the Km values of:

GLUT1

GLUT2

GLUT4

GLUT5

Back 8

GLUT1: 1-2 mM

GLUT2: 15-20 mM

GLUT4: 5 mM

GLUT5: 10 mM (fructose)

*normal blood glucose is 5 mM

Front 9

What 2 channels are involved in the exocytosis of insulin from pancreatic beta cells? Which one opens and which one closes?

Back 9

ATP-sensitive K+ channel: closes ->

Voltage-sensitive Ca++ channel: opens

Front 10

Which drugs increase insulin secretion from pancreatic beta cells by mimicking ATP and binding K+ channels?

Back 10

Sulfonylureas and Meglitinides

Front 11

Which drug decreases insulin secretion from pancreatic beta cells by opening ATP-dependent K+ channels?

Back 11

Diazoxide

Front 12

What causes GLUT4 receptors to become active? Signaling through which receptor and which pathway??

Back 12

- Insulin binds insulin receptors

- PKB pathway

- GLUT4 sequestered in intracellular vesicles gets brought to the membrane and becomes active

Front 13

What does lack of insulin in T1 diabetics do to adipocytes? What is the response of the liver hepatocytes?

Back 13

Adipocytes hydrolyze TG fat stores

Liver hepatocytes respond to increase FA content of blood by talking up FAs and metabolizing through B-ox or converting to ketone bodies ->

diabetic ketoacidosis

Front 14

What Hexokinase isoform is found in muscle tissues?

Km?

What inhibits it?

Back 14

Hexokinase I (II or III)

Km = 0.05 mM, so basically always saturated

Inhibited by: Glucose 6-P

Front 15

Where is Glucokinase (Hexokinase IV) found?

How is it different from Hexokinase I?

Back 15

Found in liver and pancreas

Km = 100x Km of Hexokinase I

Specific for glucose (no other hexoses)

Not inhibited by glucose 6-P

Front 16

How is glucokinase regulated? (Pathway)

Back 16

Low blood glucose -> buildup of Fructose 6-P in cell because of inhibition of PFK-1 -> enhanced function of GKRP (glucokinase reg protein) -> GKRP binds active cytosolic glucokinase and sequesters inside nucleus

Front 17

Where is active glucokinase?

Inactive glucokinase?

Back 17

Active: in cytosol

Inactive: sequestered in nucleus

Front 18

What is the regulation of PFK-1? Examples?

Back 18

Allosteric inhibition by: high ATP, citrate

Allosteric activation by: high ADP/AMP, fructose 2,6-bisphosphate

Other inhibition: H+ (lactate)

Other activation: Fructose 6-phosphate (substrate)

Front 19

Fructose 6-phosphate <-> Fructose 2,6-bisphosphate

Forward enzyme?

Reverse enzyme?

Back 19

Forward: PFK-2

Reverse: FBPase-2

Front 20

What is the most potent activator of PFK-1?

What is the product of the PFK-1 reaction?

Back 20

Activator: Fructose 2,6-bisphosphate

Product: Fructose 1,6-bisphosphate

Front 21

What are the 2, related roles of F26BP?

Back 21

1: allosterically activates PFK-1

2: allosterically inhibits FBPase-1

Front 22

How does glucagon affect F26BP levels? (pathway)

Overall result?

Back 22

Glucagon -> PKA -> phosphorylation of PFK-2/FBPase-2 enzyme, activating FBPase-2 domain -> breakdown of F26BP to F6P

Overall: gluconeogenesis

Front 23

How does insulin affect F26BP levels? (pathway)

Overall result?

Back 23

Insulin -> phosphoprotein phosphatase -> dephosphory. of PFK-2/FBPase-2, activating PFK-2 domain -> production of F26BP

Overall: glycolysis

Front 24

What are positive regulators of Pyruvate kinase (PK)?

Back 24

1. substrates: ADP and phosphoenolpyruvate (PEP)

2. Fructose 1,6-bisphosphate

Front 25

What are negative regulators of Pyruvate kinase (PK)?

Back 25

1. Well-fed state molecules (ATP, acetyl-CoA, LCFAs)

2. Alanine (from pyruvate)

Front 26

What regulation is specific to liver pyruvate kinase?

Back 26

Inhibited: glucagon-PKA phosphorylation

Activated: insulin-induced phosphatase activity

Front 27

What is the pathway that bypasses step 7 of glycolysis in RBCs?

Back 27

1,3-BPG -> 2,3-BPG by bisphosphoglycerate mutase

2,3-BPG -> 3-phosphoglycerate by bisphosphoglycerate phosphatase

Front 28

What is the most common deficiency causing hemolytic anemia?

2nd most common?

Back 28

1. Glucose 6-phosphate dehydrogenase (of PPP)

2. Pyruvate kinase

Front 29

What could cause pyruvate kinase-based hemolytic anemia?

Back 29

1. Deficits in activating power of F16BP

2. Change in KM for PEP and ADP

3. Enzyme levels, stability, or activity

4. NOT DIRECTLY RELATED: Inability to compensate by increasing levels of 2,3 BPG (to release more O2 from fewer RBCs)

Front 30

What chemicals inhibit glycolysis?

Back 30

1. 2-deoxyglucose (glucose analog)

2. Iodoacetamide (reacts with glyceraldehyde 3-phosphate dehydrogenase)

3. Arsenate (phosphate analog)

4. Fluoride (inhibits enolase rxn)

Front 31

What is the first step of glycolysis?

Substrates? Products? Enzyme? Energy input?

Back 31

Glucose -> Glucose 6-phosphate

Hexokinase/Glucokinase

Uses 1 ATP

Front 32

Which has a higher Km, hexokinase or glucokinase?

Back 32

Gulcokinase

Front 33

What are the 3 important results of converting glucose to glucose 6 phosphate?

Back 33

1. Invests energy (prep phase)

2. Creates a negative charge so glucose can't enter the cell

3. Glucose 6-P can be used for glycolysis, PPP, or glycogen synthesis

Front 34

What is the third step of glycolysis?

Substrates? Products? Enzyme? Energy input?

Back 34

Fructose 6-phoaphate -> fructose 1,6-bisphasphate

PFK-1

Uses 1 ATP

Front 35

What step of glycolysis cleaves the molecule?

Substrates? Products? Enzyme?

Back 35

Step 4

Fructose 1,6-bisphosphate -> DHAP + GAP

Aldolase

Front 36

What is the sixth step of glycolysis?

Substrates? Products? Enzyme? Energy output?

Back 36

Glyceraldehyde 3-phosphate (GAP) -> 1,3-bisphosphoglycerate

Glyceraldehyde 3-phosphate dehydrogenase

Makes NADH x2

Front 37

What is the seventh step of glycolysis?

Substrates? Products? Enzyme? Energy output?

Back 37

1,3-bisphosphoglycerate -> 3-phosphoglycerate

Phosphoglycerate kinase

Makes ATP x2

Front 38

What is the tenth step of glycolysis?

Substrates? Products? Enzyme? Energy output?

Back 38

Phosphoenolpyruvate -> pyruvate

Pyruvate kinase

Makes ATP x2

Front 39

Glycolysis intermediates 1,3-Bisphosphoglycerate and 3-Phosphoglycerate can be converted to ______ which is involved in ____?

Back 39

2,3-Bisphosphoglycerate (2,3-BPG)

Regulates oxygen release from hemoglobin

Front 40

Glycolysis intermediate DHAP can be converted to _____ which is involved in _____?

Back 40

Glycerol 3-phosphate

TG backbone/synth

Front 41

Glycerol 6-phosphate can be directed towards? (3)

Back 41

1. Glycolysis

2. Glycogen synthesis

3. PPP

Front 42

What additional step occurs when glycolysis occurs in anaerobic conditions?

Back 42

Pyruvate -> lactate

By lactate dehydrogenase, costing 1 NADH/pyruvate

Front 43

Glycogen is first broken into glucose monomers in the form _____, then converted to _______.

Back 43

Glucose 1-phosphate

Glucose 6-phosphate

Front 44

What enzyme does liver possess (not in muscle) that converts glucose 6-phosphate to glucose? In which pathways does this enzyme work?

Back 44

Glucose 6-phosphatase

Glycogen breakdown and gluconeogenesis

Front 45

What types of linkages are found in glycogen?

Back 45

a-1,4 (linear)

a-1,6 (branching)

Front 46

The reducing end of the glycogen molecule is the C_ end

Back 46

C4

Front 47

What is step 1 of glycogen synthesis?

Back 47

Glucose 6-phosphate -> glycose 1-phosphate

By phosphoglucomutase

Front 48

What is step 2 of glycogen synthesis?

Back 48

Glucose 1-phosphate -> UDP-glucose

By UDP-glucose pyrophosphorylase

(Activates glucose)

Front 49

What enzyme transfers activated glucose to the nonreducing end of glycogen?

Back 49

Glycogen synthase

Front 50

What enzyme catalyzes the generation of branches in glycogen?

Back 50

Glycosyl 4,6 transferase

Front 51

What protein begins de novo synthesis of glycogen?

Back 51

Glycogenin

Front 52

What is the enzyme of glycogenolysis that catalyzes the removal of single glucose a-1,4 linkages? What does it produce?

Back 52

Glycogen phosphorylase

Glucose 1-phosphate

Front 53

What are the 2 activities of the de-branching enzyme of glycogenolysis? What do they produce?

Back 53

Glucosyl 4,4 transglycosidase (eventually = glucose 1-phosphate)

a-1,6 glucosidase (= glucose)

Front 54

What hormone triggers glycogenolysis in liver? In muscle?

Back 54

Liver: glucagon

Muscle: epinephrine

Front 55

What cofactor does glycogen phosphorylase require?

Back 55

Pyridoxal phosphate (PLP)

active form of B6

Front 56

Type 0 Glycogen Storage Disease:

Enzyme affected?

Primary organ?

Symptoms?

Back 56

Glycogen synthase (makes 1,4 linkages)

Liver

Low blood glucose, high ketone bodies, early death

Front 57

Type Ia (von Gierke's) Glycogen Storage Disease:

Enzyme affected?

Primary organ?

Symptoms?

Back 57

Glucose 6-phosphatase (G6P -> glucose)

Liver

Enlarged liver, kidney failure

Front 58

Type II (Pompe's) Glycogen Storage Disease:

Enzyme affected?

Primary organ?

Symptoms?

Back 58

Lysosomal glucosidase (cuts 1,6 branches)

Skeletal and cardiac muscle

Infantile form: death by 2

Juvenile form: muscle defects

Adult form: as in muscular dystrophy

Front 59

Type IIIa (Cori's or Forbes's) Glycogen Storage Disease:

Enzyme affected?

Primary organ?

Symptoms?

Back 59

Debranching enzyme

Liver, skeletal, and cardiac muscle

Enlarged liver in infants, myopathy

Front 60

Type IV (Andersen's) Glycogen Storage Disease:

Enzyme affected?

Primary organ?

Symptoms?

Back 60

Branching enzyme

Liver, skeletal muscle

Enlarged liver and spleen, myoglobin in urine

Front 61

Type V (McArdle's) Glycogen Storage Disease:

Enzyme affected?

Primary organ?

Symptoms?

Back 61

Muscle phosphorylase (removes 1,4 linkages)

Skeletal muscle

Exercise-induced cramps and pain, myoglobin in urine

Front 62

What is the relationship between glycogen synthase, glycogen phosphorylase, and phosphorylation?

Back 62

Both are phosphorylated/de-phosphorylated at the same time

Glycogen synthase is active when DEphosphy

Glycogen phosphorylase is active when phosphor.

Front 63

What enzyme phosphorylates glycogen phosphorylase? How is it activated?

Back 63

Phosphorylase kinase

Activated by phosphorylation

Front 64

How does phosphorylase kinase get phosphorylated/activated?

Back 64

GPCR -> cAMP -> PKA

Front 65

What protein dephosphorylates glucose phosphorylase? What helps it to act in the liver?

Back 65

Phosphorylase phosphatase 1 (PP1)

Glucose

Front 66

What protein phosphorylates (deactivates) glycogen synthase? Dephosphorylates (activates)?

Back 66

Phosphorylates: Glycogen Synthase Kinase 3 (GSK3)

Dephosphorylates: PP1

Front 67

What substances can allosterically activate Glycogen synthase?

Back 67

Activate: glucose or glucose 6P

Front 68

What protein activates PP1 when phosphorylated, and then removes PP1 from the complex when further phosphorylated?

Back 68

Gm