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Glycogen synthesis and metabolism Flashcards

1
Q

What type of molecule is glycogen? What is it made up of?

A

Polysaccharide

Glucose monomers

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2
Q

What is the function of Glycogen?

A

Storage of glucose

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3
Q

Where is glycogen stored? How much is stored in each location? What is the glycogen used for in each location?

A

Liver- 100g- Maintains blood glucose

Muscle- 400g- Supplies energy during muscle contraction

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4
Q

Why is glucose stored as glycogen?

A
  1. Less osmotically active than glucose
  2. Easier to mobilize to and from liver to maintain blood glucose
    and to and from muscles to generate ATP
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5
Q

What is required before glycogen can be formed from glucose?

A

The primer glycogenin. Glucose must attach to glycogenin

Glucose – 6 – phosphate (G6P)

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6
Q

Which bond is used to form a chain of glucose molecules?

A

Alpha 1,4- glucosidic bond between carbon atoms

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7
Q

Which bond is used to form branches in a chain of glucose molecules?

A

1,6 carbon link forms branches

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8
Q

How is glycogen stored? Why is it stored in this manner?

A

As a macroglycogen. It is a large molecule so more enzymes can work to break the molecule down and build it up quicker

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9
Q

When is glycogen produced and stored?

A

During rest and when there is an increase in glucose concentration

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10
Q

What is the name for glycogen break down?

A

Glycogenolysis

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11
Q

Which enzyme is first used to break down glycogen branches? Which enzyme is used to break down the actual chain?

A

a-1,6-glucosidase

Glycogen phosphorylase

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12
Q

What is glycogenin

A

A primer used in the formation of glycogen

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13
Q

Describe the 4 steps in glycogen synthesis

A

Step 1: G6P –> G1P
Step 2: G1P –>UDP-glucose using uridine triphosphate (UTP)
Step 3: UDP-glucose added to growing glycogen chain attached to the glycogenin primer.
(Glycogen synthase adds UDP by catalysing the 1,4-glycosidic bond)
Step 4: Branches added to growing glucose chains using enzyme glycogen 4,6 transferase to created 1,6 bonds.

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14
Q

Which enzyme catalyses the formation of glycogen branches?

A

glycogen 4,6 transferase

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15
Q

Which enzyme catalyses the addition of glucose to glycogen chain?

A

Glycogen synthase

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16
Q

What happens to glycogen in the liver? When does this occur?

A

G6P is de-phosphorylated to glucose to go directly in the blood stream to maintain glucose homeostasis.

Occurs during periods of fasting to maintain constant glucose levels.

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17
Q

What happens to glycogen in muscles during?

A

All glycogen goes directly into glycolysis to produce energy directly so never becomes glucose.
Used as a medium –term course of energy

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18
Q

What happens to lactate during anaerobic respiration?

A

During anaerobic respiration, lactate produced by glycolysis can be recycled via the Cori cycle.

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19
Q

Which biological pathway produces lactate?

A

Glycolysis

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20
Q

Name the molecules which control glycogen production

A
  1. Insulin
  2. Glucagon
  3. Adrenaline (aka Epinephrine)
  4. Calcium
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21
Q

Which hormone produces insulin and glucagon? How is there relationship described?

A

Pancreas

Antagonistic

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22
Q

Describe how insulin controls glycogen

A

Stimulates glycogen production by:
Activating glycogen synthase
Inhibiting glycogen phosphorylate

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23
Q

When is insulin most often released?

A

After a meal

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24
Q

Describe how glucagon controls glycogen

A

Stimulates glycogen breakdown by:
Inhibiting glycogen synthase
Activating glycogen phosphorylase

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25
When is glucagon released?
Between meals
26
What effect does phosphate (PO4) have on Gs and Gp?
GS is inhibited by the addition of PO4 while GP is activated by PO4
27
Describe how adrenaline and calcium control glycogen
Stimulates glycogen breakdown by: Inhibiting glycogen synthase Activating glycogen phosphorylase (add phosphate)
28
Where does glycogen, insulin, calcium and Adrenalin work?
Insulin- Liver and muscle Glycogen- Liver only (no receptors in muscle) Calcium and adrenalin- only in muscle
29
When does glycogen break down mostly occur?
During exercise
30
How does Glucose-6-phosphate effect glycogen synthesis?
Allosteric activator
31
What is Mc Ardle’s disease? What is the cause of Mc Ardle’s disease? How many mutations have been found?
Glycogen storage disease type 5. Unable to produce muscle phosphorylase. Can not break down muscle glycogen Cause- Genetic defect in the muscular glycogen phosphorylase enzyme (myophosphorylase) gene – PYGM 95 mutations
32
What is the pathophysiology of Mc Ardle’s disease?
Cannot breakdown glycogen in the muscle so experience muscle weakness. Experience a “second wind” during exercise caused by re-uptake of glucose in the muscle. Rapid exercise will cause muscle damage, cramping due to depletion of ATP.
33
What is the Ischemic forearm test?
Involves measuring plasma lactate and ammonia produced as a result of forearm exercise under ischaemic conditions in a fasted subject.
34
Why is lactate and ammonia measured in the Ischemic forearm test?
Both lactate and ammonia increase during workload- exercise. If lactate alone is measured the test may not distinguish between patients with defective glycolysis and those in whom poor effort has led to minimal lactate production
35
Why is the Ischemic forearm test potentially dangerous in patients with McArdle’s disease. Explain your answer.
There is a risk of rhabdomyolysis (the death of muscle fibers and release of their contents into the bloodstream).
36
What is Heteronormativity?
The belief that people only fall into distinct and complementary genders (male and female) with natural roles in life. It assumes that heterosexuality is the norm or default sexual orientation, and that sexual and marital relations are most (or only) fitting between people of opposite sex.
37
What is Myoglobin? Function?
Cytoplasmic hemoprotein, found only in cardiac myocytes and skeletal muscle fibers. Reversibly binds O2 by its heme residue
38
What is Creatine kinase?
Enzyme that catalyzes the rephosphorylation of ADP to ATP using creatine phosphate as the phosphorylation reservoir. During exercise ATP is converted to ADP
39
What is HERS disease?
A genetic disorder of glycogenolysis caused by deficiency of hepatic glycogen phosphorylase. Results in an inability to break down glycogen in liver cells.
40
What are the signs and symptoms of HERS disease?
Enlarged liver (hepatomegaly) low blood sugar (hypoglycemia) High levels of ketones in the blood (ketosis) Delayed development
41
Effect of HERS disease in adults?
Signs and symptoms tend to improve with age; most adults with this condition do not have any related health problems.
42
What is Dextros?
Simple sugar, identical to glucose chemically, made from corn. Given intravenously to increase blood sugar.
43
What is a Ketogenic diet?
High-fats, moderate-proteins, and very-low-carbohydrates. | Forces body to undergo gluconeogenesis and ketogenesis.
44
What is gluconeogenesis and ketogenesis?
Gluconeogenesis- Production of glucose from lactic acid, glycerol, and the amino acids alanine and glutamine Ketogensis- Formation of keton bodies from Fat break down
45
What are the products of fat break down during ketogensis?
Fat---> acetoacetate-----> beta-hydroxybutyrate and acetone
46
What are the main ketone bodies?
beta-hydroxybutyrate and acetone
47
What is ketoacidosis?
Life-threatening condition where ketone bodies are produced in extremely larger concentrations, causing blood ph to be acidic.
48
Why is a ketogenic diet safe?
Keton bodies produced in small amounts so it does not alter blood PH Ketone bodies also can cross the blood-brain barrier to provide an alternative source of energy to the brain.
49
What does the inheritance pattern of McArdle disease?
autosomal recessive
50
What is an IV bolus
Large amount of of fluid or medication given intravenously to speed up or increase a response
51
What is the second wind effect?
Sudden decrease in heart rate (HR) and an improved exercise tolerance occurring after a few minutes of exercise. Represents a lag in the supply of energy for physical activity as a result of deficient glycolytic muscle metabolism and the time taken for the release of glucose from liver glycogen stores and fatty acid oxidation to provide the required energy.
52
What is the main test for McArdle disease? What do the results show in a positive test?
Muscle biopsy- Vacuoles with excessive glycogen and a lack of staining for glycogen phophorylase
53
Which mutation is most common in PYGM?
R50X mutation
54
Which chromosome is the PYGM gene found?
CR 11
55
What is the inheritance pattern for HERS disease? Which gene is affected and what chromosome is this gene on?
autosomal recessive trait. Mutation on PYGL gene which encodes for the liver phosphorylase enzyme gene on Ch 14
56
Why is Creatin kinase, myoglobin, potassium and urea high in those with Mc Ardles disease?
Increased creatine- Indicates muscle damage. This causes CK to leak from cells into blood serum. High myoglobin- Rhabdomyolysis is the breakdown of damaged skeletal muscle. Muscle breakdown causes the release of myoglobin into the bloodstream. If you have too much myoglobin in your blood, it can cause kidney damage High urea- released during muscle damage-protein from muscle break down. This is broken down into urea and released into the blood. This is all from muscle not diet. High potassium- due to muscle break down as there is a lot of potassium in muscle cells (all cells)
57
What effect does exercise have on PH?
pH does not decrease with exercise If the addition of lactic acid and other by products of airobic respiration exceeds your body's clearance (blood PH buffers), your blood pH decreases.
58
What are the treatment options for Mc ardles disease?
1. Carbohydrate-rich diet: (20% fat, 15% protein and 65% carbohydrate) A low carbohydrate diet is not recommended because it will deplete liver glycogen and reduce the amount of glucose released into the blood stream. This will lead to hypoglycemia (low blood sugar) when the person becomes active. 2. consume a sugary drink or snack before participating in strenuous activity to provide the body with immediate energy before the second wind is achieved. 3. Ketogenic diet- ketone bodies from fatty acids become a significant energy source for extra hepatic tissues instead of glucose
59
Which enzyme catalysis the conversion of G1P to G6P –
Phosphoglucomutase
60
Describe the stages of glycogen break down
Step 1: breakdown of glycogen branches – debranching enzyme α-1,6-glucosidase Step 2: removal of terminal glucose molecules by breaking 1,4 links – enzyme glycogen phosphorylase. Step 3: conversion of G1P to G6P – enzyme phosphoglucomutase.

Metabolism (9 decks)

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