M104 T2 L7 Flashcards

1
Q

In what form are polysaccharides stored in the body and where?

A

stored in granules
predominantly in liver and muscle
as an E reserve

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2
Q

From what process and product is glycogen formed?

A

glycogenesis

dietary glucose

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3
Q

What is the role of liver glycogen?

A

to maintain plasma glucose levels between meals

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4
Q

What is the role of muscle glycogen?

A

to sustain muscle contraction

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5
Q

What happens to glycogen between meals?

A

it is degraded in the liver
by the glycogenolysis pathway to produce glucose-1-phosphate
or it is broken down in muscle to provide the E to support muscle contraction

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6
Q

What happens to glucose-1-phosphate when it is converted from glycogen in the liver?

A

it can be converted to free glucose and exported into the bloodstream to maintain plasma glucose levels

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7
Q

What percentage of the weight of the liver and of the muscle comes from glycogen when in fed state?

A

liver - 10%

muscle - 2%

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8
Q

What percentage of human body weight is made up of muscle and of the liver?

A

muscle - 40%

liver - 2.5%

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9
Q

Overall, is more glycogen stored in muscle tissue or in the liver?

A

muscle tissue
40% of body weight x 2% = 0.8
liver: 2.5% x 10% = 0.25

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10
Q

Can the liver sustain glucose metabolism for 24 hours?

A

no - it contains less glycogen than is required to

it therefore requires de novo synthesis by gluconeogenesis

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11
Q

In what form is glycogen stored in the body?

A

found in the form of granules within cells

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12
Q

What is the structure of glycogen?

A
highly branched 
consists of (α-1,4) linked glucose molecules with an (α-1,6)branch every 8-14 glucose residues
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13
Q

What is an imporant structural feature of glycogen and why?

A

a large number of ends at which phosphorylase and glycogen synthase can act to ensure rapid breakdown and resynthesis

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14
Q

How many glucose residues does it take to come across an (α-1,6) branch?

A

every 8-14 glucose residues

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15
Q

How are glycogen molecules linked?

A

(α-1,4)

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16
Q

Where si the branch on glycogen molecules?

A

(α-1,6)

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17
Q

Which linkages are used to form glycogen?

A

α-D-Glucose

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18
Q

What are the two linkages used to form glycogen?

A

α-1,4 linkage

α-1,6 linkage

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19
Q

What happens in cells in times of metabolic need?

A

mobilisation - they switch on the breakdown of stored glycogen very rapidly using a combination of signals
the breakdown products meet different needs in liver and muscle

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20
Q

What is the relationship between bg and liver glycogen stores throughout the day?

A

glycogen stores rise after a meal in response to an increase in bg
between meals glycogen stores fall as glucose is released from liver glycogen to stabilize the bgc
overnight glycogen stores are mobilized to help maintain bgc

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21
Q

What are the α1-4 linkages in glycogen broken down by?

A

phosphorolysis

catalysed by glycogen phosphorylase

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22
Q

What happens during phosphorolysis?

A

glycogen phosphorylase removes single units from non-reducing ends of glycogen to form G-1-P
ATP isn’t involved

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23
Q

What is the role of phosphate in phosphorolysis?

A

the phosphate acts like water does in hydrolysis reactions

it can only break α-1,4 links up to within 4 glucose units from a branch point

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24
Q

What is the effect of transferase activity of the debranching enzyme?

A

it removes 3 residues from the branch and transfers them to the end of another chain in α-1,4-linkage
phosphorolysis

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25
Q

What is the role of the α-1,6-glucosidase activity of the debranching enzyme during phosphorolysis?

A

to break the α1-6 linkages of the single glucose unit left at the branch
to cleave the bond to form free glucose by hydrolysis
does not involve phosphate
the chain can then be broken down by phosphorylase until it meets the next branch point

26
Q

What percentage of glucose mobilized from glycogen is ‘free’ glucose rather than glusoe-1-phosphate?

A

about 10%

27
Q

Why can’t Glu-1-P be exported to the blood from muscle tissue?

A

bc muscle lacks Glucose-6-phosphatase

28
Q

What is glycogen formed from?

A

UDP-glucose

29
Q

What is the role of glycogen synthase in glycogenesis?

A

to add glucose units in α-1,4-linkage onto the glycogen chain using UDP-glucose

30
Q

What si the role of UDP-glucose in glycogenesis?

A

it donates the first glucosyl residue and attaches it to the amac tyrosine in the glycogenin

31
Q

What si the role of glycogenin in glycogenesis?

A

it extends the glucose chain by up to 7 additional residues from UDP-glucose via α-1,4-linkages

32
Q

What are the limitations of glycogen synthase in glycogenesis?

A

can only do to a pre-existing chain of more than four glucosyl residues
can’t make branches

33
Q

What is the role of branching enzyme?

A

to creates the branches of the glycogen molecule

34
Q

Why is glycogen is a good E store?

A

bc it can be mobilised very rapidly

35
Q

What are the enzymes phosphorylase and glycogen synthase regulated by?

A

hormones, stress and muscle contraction

36
Q

What is a benefit of the branched structure of glycogen?

A

provides a large number of ends at which the polymer can be added to or broken down

37
Q

Why is glycogen is a bad E store?

A

bc glucose is hydrophilic and associates with water increasing the overall weight and bulk

38
Q

Where is glycogenolysis greatly accelerated?

A

In the liver in between meals or during extended fasting, when glucose is required for glycolysis by the brain and red blood cells
In muscle to fuel glycolysis during vigorous exercise

39
Q

Why is glycogenesis activated?

A

to replenish liver glycogen stores after feeding

to replenish muscle stores when exercise ceases

40
Q

What substances is glycogen phosphorylase in muscle allosterically regulated by?

A

AMP, ATP and glucose-6-phosphate

41
Q

What is the role of AMP?

A

it activates phosphorylase

42
Q

When is AMP present?

A

when ATP is depleted during muscle contraction

43
Q

What do ATP and glucose-6-phosphate inhibit? WHat are they signs of?

A

phosphorylase

high E levels

44
Q

What happens when ATP and glucose-6-phosphate are plentiful?

A

glycogen breakdown is inhibited

45
Q

What is glycogen synthase allosterically activated by?

A

glucose-6-phosphate

46
Q

What is glycogen metabolism regulated by?

A

covalent modification - the addition (and removal) of a phosphate group

47
Q

What is the (de)phosphorylation of glycogen catalysed by?

A

phos - protein kinases, reversible modification

dephos - protein phosphatases

48
Q

What does the cAMP cascade result in?

A

the phosphorylation of a hydroxyl group in a serine residue of glycogen phosphorylase, which promotes transition to the active state

49
Q

What is the effect of phosphorylated enzymes being less sensitive to allosteric inhibitors?

A

even if cellular ATP levels and glucose-6-phosphate are high, phosphorylase will be activated

50
Q

What is glycogen synthase converted into when is undergoes phosphorylation?

A

the ‘b’ (less active’) conformation

glycogen synthesis is inhibited

51
Q

What is the difference between the ‘a’ and ‘b’ forms of enzymes?

A

A - active form of enzyme, is independent of allosteric regulators
B - a form of enzyme dependent on local allosteric controls

52
Q

When is the phosphorylated form of metabolic enzymes the active or inactive form?

A

active - if it is involved in an catabolic reaction (breaking down)
inactive - if it is involved in an anabolic reaction (building up)

53
Q

What is the difference between a-1,4 and a-1,6 linkages in a glycogen mlc?

A

4 - make straight linear connections

6 - makes branched non-linear connections

54
Q

What are the intermediates of glycogenolysis in the muscle?

A

glycogen < G1P < G6P < pyruvate

pyruvate turns into lactate and co2

55
Q

What are the intermediates of glycogenolysis in the liver?

A

glycogen < G1P < G6P (+ G6Pase) < glucose

56
Q

What enzymes are used to break a-1,4 and 1-1,6 linkages?

A

1,4 - phosphorylase

1,6 - debranching enzyme

57
Q

How does the synthesis of a glycogen molecule begin?

A

the synthesis of a new molecule of glycogen is carried out by glycogenin
it carries out the primary function

58
Q

What does the primary function involve?

A

when glycogenin accepts the first glucosyl residue from UDP glucose

59
Q

How does the branching enzyme work?

A

it transfers a block of 7 residues from a growing chain it creates a new branch with an α-1,6-linkage

60
Q

What is the role of protein kinase?

A

to convert phosphorylase b into phosphorylase a

to convert glycogen synthase-b into glycogen synthase a

61
Q

What is the role of protein phosphatase?

A

to convert phosphorylase a into phosphorylase b

to convert glycogen synthase a into glycogen synthase-b