Biochem - Glycogen Synthesis & Breakdown

Front 1

Glycogen synthesis is called

Back 1

Glycogenesis

Front 2

What tissues are insulin independent?

Back 2

Erythrocytes
Leukocytes
Lens of eye
Cornea
Liver
Brain

Front 3

What main tissues are insulin sensitive?

Back 3

Most tissues including adipose and muscles

Front 4

Summarize the action of GLUT4 transporters in the presence of insulin in the blood

Back 4

Insulin binds to its receptor, the activated receptor causes GLUT4 recruitment to cell membrane, vesicles containing GLUT4 transporters fuse with membrane and cause an increase in glucose uptake into cell, transporters are moved out of membrane and into cytoplasm when insulin levels drop, vesicles housing GLUT4's close and become endosomes until recruited again

Front 5

All diabetes group of disorders are characterized by

Back 5

Hyperglycemia

Type I: absolute deficiency
Type II: relative deficiency (can even be normal at first onset)

Front 6

What step involving glucose is involved in all glucose utilization pathways?

Back 6

Transfer of terminal phosphate group from ATP to glucose, forming G6P

G6P will not be taken up by transporters, ensuring it will stay in cell for further metabolism

Front 7

What are the 4 characteristics of Hexokinase? Glucokinase?

Back 7

Hexokinase
Km = 0.1mM
Constitutive - not induced
In general tissues
Inhibited by G6P

Glucokinase
Km = 10mM
Induced by insulin
Used by liver
Not inhibited by G6P

Front 8

How does Hexokinase create facilitated transport of glucose by phosphorylation?

Back 8

Glucose --> G6P causes [glucose] inside cell to be less, therefore creating favorable gradient for continued influx

Front 9

What molecule causes inactivation of GK?

Back 9

Fructose 6-phosphate

Although not inhibited by G6P similar to Hexokinase, F6P concentraions can cause GK to translocate into the nucleus, bind to it's regulatory protein, and become inhibited. Glucose will cause the GK to translocate from the regulatory protein when glucose concentrations are higher than F6P and glucose needs converted

Front 10

Where is glucokinase found?

Back 10

Liver

Front 11

How does G6P convert to G1P?

Back 11

The phosphate on G6P is tranferred to the carbon-1 position yielding G1P via an enzyme called phosphoglucomutase

Front 12

What does phosphoglucomutase do?

Back 12

Causes intramolecular transfer of a group from one position to another

Front 13

The only step common between glycogen synthesis and breakdown is:

Back 13

G6P to G1P

Front 14

What energy is required per molecule of glucose for gycogenesis?

Back 14

2 total energy subunits, 1 for phosphorylation of glucose (UTP) and one to regenerate UTP from UDP + ATP

Front 15

Summarize glycogenesis, beginning with glucose (include enzymes)

Back 15

Terminal P on ATP transferred to glucose --> G6P (hexo/glucokinase) --> P on 6-carbon transferred to 1-carbon (phosphoisomutase) --> UTP is broken to yield a UDP connected to the G1P, UDPG, and the 2 pyrophosphate leftover from UTP conversion is hydrolyzed to yield Pi --> UDP is released and 2 glucose molecules become linked with an alpha-1,4 bond at the reducing end of the glycogen primer (glycogen synthase) --> UTP is regenerated from UDP via utilization of ATP to ADP (nucleotide diphosphokinase)

Front 16

What protein is used on the reducing end of the glycogen primer?

Back 16

Glycogenin

Front 17

How does the glycogen primer become activated or usable for glycogenesis without previous glucose attachments?

Back 17

OH oh tyrosine or serine residues act as initial site for glucose addition. Glycogenin is capable of autoglucosylation and catalyzes the transfer of glucose from UDPG and be further elongated via GS (glycogen synthase)

Front 18

Summarize branch formation during glycogenesis

Back 18

5-8 glucose residues linked alpha-1.4 are cleaved via glucosyl-4:6 transferase and reattached at the interior via alpha-1,6 bond

Front 19

What enzyme cleaves glucose segments to replace them internally for branching?

Back 19

Glucosyl-4:6 transferase
Known as the 'branching enzyme'

Front 20

How far apart can branching be in glycogen formation?

Back 20

4 residues away

Front 21

What is the purpose of branching in glycogen?

Back 21

More non-reducing ends allows more enzymes to access and increases frequently of glycogen formation and breakdown

Front 22

Why is glucose stored in the form of glycogen rather than individual molecules?

Back 22

Glucose is highly osmotic whereas glycogen is not. Too much glucose storage can lead to cell lysis due to excess water uptake

Front 23

The degradation of glycogen is termed

Back 23

Glycogenolysis

Front 24

The first cleavage in glyconeolysis is cleavage of what bond?

Back 24

The terminal alpha-1,4 bond via glycogen phosphorylase and phosphorylation of that glucose molecule with Pi

Front 25

T/F the first step in glycogenolysis requires ATP?

Back 25

False - the glucose molecule is phosphorylated with Pi to yield G1P

Front 26

What does glycogen phosphorylase do?

Back 26

Catalyzes sequential removal of glucose from nonreducing end of glycogen to form G1P

Front 27

The debranching enzyme consists of what catalytic activies?

Back 27

Transferase: transfers terminal 3 glucose molecules to different branch and expose alpha-1,6 glucose linkage

Alpha-1,6 glucosidase releases one glucose

Front 28

What is the function of transferase in glycogenolysis?

Back 28

Phosphorylase can only break down glycogen up to 4 units from a branch point. Transferase takes last 3 units and adds on to nonbranched area for phosphorylase to break the bonds and release glucose while glucosidase cleaves the alpha-1,6 bond of remaining glucose

Front 29

Alpha-1,6 bonds are cleaved by

Back 29

Alpha-1,6 glucosidase

Front 30

Alpha-1,4 bonds are cleaved by

Back 30

Glycogen phosphorylase

Front 31

G1P from glycogenolysis is transformed to G6P via

Back 31

Phosphoglucomutase
Step same in both pathways

Front 32

G6P to glucose occurs via what enzyme? and where?

Back 32

Glucose-6-phosphatase
Enzyme is only present in liver, muscle does not have ability so G6P is utilized for glycolysis in muscle tissue rather than exchanged for glucose

Front 33

Glycogenolysis and glycogenesis occur in what part of the cell?

Back 33

Cytosol

Front 34

The two types of regulation for the glycogen synthesis and degradation pathways are what type?

Back 34

Hormonal
Allosteric

Front 35

The two regulatory enzymes for general (de)phosphorylation are what type?

Back 35

Kinase - transfers P onto enzyme from ATP

Phosphotase - hydrolyzes P off of enzyme

Front 36

Glycogen synthase is active when it is in what state?

Back 36

Non-phosphorylated

Front 37

Phosphorylase is active when it is in what state?

Back 37

Phosphorylated

Front 38

The two enzymes that oppose each other in the glycogen pathways are active in what states?

Back 38

Glycogen synthase - nonphosphorylated
Phosphoryalase - phosphorylated

Front 39

Phosphorylase b is what?

Back 39

Inactive form of phosphorylase

Front 40

During a fasting state? What status do we want our enzymes in?

Back 40

Phosphorylated
Glycogen synthase will be inactive and phosphorylase will be active for breakdown

Front 41

Compare phosphotase and phosphorylase

Back 41

Phosphotase: enzyme that hydrolyzes phosphates from other enzymes to yield Pi

Phosphorylase: enzyme that cleaves alpha-1,4 bond during glycogenolysis and is rendered inactive by phosphotase

Front 42

What is phosphorylase kinase?

Back 42

Adds the phosphate group onto phosphorylase, rendering it active for glycogen breakdown

Front 43

Two major hormonal activators of glycogenolysis are:

Back 43

Glucagon
Epinephrine

Front 44

Glucagon is secreted from

Back 44

Alpha pancreatic cells

Front 45

Glucagon has effects in what tissue?

Back 45

Liver

Front 46

Epinephrine is secreted from

Back 46

Adrenal medulla

Front 47

Which hormone regulator has more than one target tissue effect?

Back 47

Epi - both muscle and liver whereas glucagon is ONLY liver

Front 48

The activation of PKA via glucagon phosphorylates what three things, and what effect do they have once phosphorylated?

Back 48

Glycogen phosphorylase - ACTIVE
Glycogen synthase - INACTIVE
Inhibitor-1 - ACTIVE (for inhibition of phosphotase)

Front 49

How is cAMP broken down via insulin stimulation?

Back 49

Changed to AMP via phosphodiesterase

Front 50

Phospholipase C, when epinephrine binds to alpha receptors, does what?

Back 50

Hydrolyzes PIP2 to IP3 and DAG

Front 51

Ca++ is released from endoplasmic reticulum via epinephrine receptor activation, and binds to what?

Back 51

Calmodulin

The C++-calmodulin complex activates phosphorylase kinase as well as phosphorylation of glycogen synthase (inactivation)

Front 52

PKC, activated by Ca++ and DAG phosphorylates what?

Back 52

Glycogen synthase, renders it inactive

Front 53

The three main effects insulin is thought to have are

Back 53

Limit cAMP production
Activate hepatic (liver) protein phosphatases
Activate phosphodiesterase converting cAMP to AMP

Front 54

When glycogenesis is active the insulin:glucagon ratio is

Back 54

High - a lot of insulin in the blood is causing glycogen synthesis

Front 55

Hormone mediated regulation can be overridden by what?

Back 55

Allosteric regulation - prevents problems due to 'false alarms' of hormone release

Front 56

The allosteric inhibitors of liver glycogenolysis/glycogen phosphorylase are:

Back 56

Glucose
G6P
ATP

Front 57

What allosteric activator causes activation of glycogen synthase in the liver?

Back 57

G6P

Front 58

What are the allosteric activators and inhibitors in muscle for glycogen synthesis and degradation?

Back 58

Activators of GS: G6P

Inhibitors of glycogen phosphorylase: G6P, ATP
Activators of glycogen phosphorylase: Ca++, AMP (indicates that ATP has been hydrolyzed and more glucose is needed)

Front 59

Glycogen levels in muscle do not vary with a fasting/feeding cycle due to

Back 59

Glucagon - has no effect on muscles

Front 60

Summarize type I glycogen storage disease

Back 60

Von Gierke's disease
Cannot take glucose to G6P, affects both pathways and cannot provide glucose in fasting state
Symptoms: enlarged liver, hypoglycemia, ketosis, affects liver and kidney

Front 61

Summarize type III glycogen storage disease

Back 61

Cori's disease
Debranching enzyme is affected, cannot remove the group of three moieties and reattach
Affects muscle and liver

Front 62

Summarize Andersen's disease

Back 62

Type IV glycogen storage disease
Branching enzyme is affected, cannot change alpha-1,4 bond to alpha-1,6
Symptons: cirrhosis of liver, and eventual failure by age 2

Front 63

Type V glycogen storage disease is

Back 63

McArdle's disease
Problem with phosphorylase, cannot breakdown glycogen ONLY in muscle
Limited ability to perform exercise

Front 64

Hers' disease is

Back 64

Type Vi glycogen storage disease
Affects phosphorylase in liver
Cannot provide glucose in fasting state, same symptoms as Type I but milder