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FM, G2E and S2C > Systems to Cells > Flashcards

Systems to Cells Flashcards

1
Q

What makes up ATP?

A

An adenine base connected to a five carbon ribose sugar which is then joined to three phosphates (alpha, beta and gamma). The phosphate bonds are very high in energy and chemical energy is stored in the last (gamma) phosphate group.

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2
Q

How is energy released from ATP?

A

Energy is released when the gamma phosphate is broken off in hydrolysis.

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3
Q

Glycolysis breaks glucose down into…

A

Pyruvate

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4
Q

Under aerobic conditions, pyruvate is converted into…

A

Acetyl-CoA which enters the TCA cycle

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5
Q

Under anaerobic conditions, pyruvate is converted into…

A

Lactate therefore it can still be used as a fuel however this is less efficient.

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6
Q

How many ATP does one glucose yield?

A

36

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7
Q

How is glucose stored in plants and humans?

A

As starch in plants and glycogen in humans

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8
Q

Name some of the biosynthetic reactions in which glucose is involved.

A

Making all amino acids, making membrane lipids, making nucleotides for DNA and RNA, etc.

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9
Q

Why does the brain have an absolute requirement for glucose?

A

The brain does not store its own fuel and cannot use others efficiently.

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10
Q

What is released when blood glucose increases?

A

Insulin is released from pancreatic beta-cells in Islets of Langerhans

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11
Q

What is released when blood glucose falls?

A

Glucagon is released from pancreatic alpha-cells in Islets of Langerhans

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12
Q

What is gluconeogenesis?

A

A metabolic pathway which results in the generation of glucose from non-carbohydrate carbon substrates such as lactate and amino acids.

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13
Q

Which is more energy dense: fat or carbohydrates?

A

Fat is more energy dense

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14
Q

What is used as an energy source during rest and low intensity exercise?

A

Fats and blood glucose

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15
Q

Why is fat not used as the primary energy source in higher intensity exercise?

A

It is slower to mobilise and needs more oxygen and as oxygen is in short supply during exercise, this is less efficient.

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16
Q

What is the main energy source during high intensity exercise?

A

Glycogen stores

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17
Q

What happens when glycogen stores are depleted during high intensity exercise?

A

Other forms of fuel, such as protein, may be used

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18
Q

Which enzyme converts glucose to glucose-6-phosphate?

A

Hexokinase

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19
Q

Which enzyme converts glucose-6-phosphate to glucose?

A

Glucose-6-phosphatase

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20
Q

Which enzyme can change glucose-6-P to glucose-1-P and vice versa>

A

Phosphoglucomutase

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21
Q

What enzyme joins glucose-1-P subunits to form glycogen?

A

Glycogen synthase

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22
Q

Which enzyme breaks down glycogen into glucose-1-P subunits?

A

Glycogen phosphorylase

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23
Q

What kind of linkages join the glucose subunits within glycogen?

A

alpha-1,4 linkages

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24
Q

What is phosphorylation?

A

The covalent addition of a phosphate, transferred from ATP, by the action of a class of enzymes known as kinases. This is reversible and the removal of the phosphate is catalysed by a group of enzymes called phosphatases.

25
Q

Why does phosphorylation alter the 3D conformation of the target protein?

A

Because of the high density of the protein-bound phosphoryl group, -2 at physiological pH. These often make salt bridges with nearby arginine or lysine residues which are positively charged.

26
Q

What are the two main classes of kinase?

A

Those which phosphorylate tyrosine residues and those that phosphorylate serine/threonine residues.

27
Q

The presence of glucagon causes a rise in cAMP. What effect does this have?

A

This activates protein kinase A which then phosphorylates multiple enzymes including glycogen synthase and glycogen phosphorylase. This will turn on glycogen phosphorylase and turn off glycogen synthase.

28
Q

Insulin activates protein phosphatase-1. What effect does this have?

A

This dephosphorylates glycogen synthase and glycogen phosphorylase, turning glycogen phosphorylase off and glycogen synthase on.

29
Q

To be active, glycogen phosphorylase must…

A

be phosphorylated

30
Q

To be active, glycogen synthase must…

A

be dephosphorylated

31
Q

Name two positive amino acids which form salt bridges with phosphate.

A

Arginine and lysine

32
Q

What governs the rates of metabolic pathways?

A

The activity of key enzymes

33
Q

Reversible covalent modification, such as phosphorylation, is a good example of…

A

allosteric modulation of enzyme activity

34
Q

In cases where the direction of a metabolic pathway has to be reserved, the pathway is controlled at…

A

an irreversible step

35
Q

What are the rate limiting steps in the glycolytic pathway?

A

1) The phosphorylation of glucose by hexokinase or glucokinase
2) The phosphorylation of fructose-6-phosphate to form fructose-1,6-bisphosphate by fructose-6-phosphate kinase

36
Q

How is Type 1 diabetes caused?

A

Type 1 diabetes is caused by β-cell destruction and may be of autoimmune or idiopathic cause. Insulin is not produced. This affects around 10% of diabetics.

37
Q

How is Type 2 diabetes caused?

A

Type 2 diabetes is caused by insulin resistance and eventual β-cell dysfunction. This affects around 90% of diabetics.

38
Q

Brown bears go through cycles of high calorie intake (20,000/day) and become obese with long periods of no exercise. In humans this would predispose to T2D. Why are brown bears not predisposed to T2D?

A

They turn on/off insulin resistance to maintain blood sugar with their insulin and glucose levels remaining stable throughout the year. Gene expression changes are responsible for this with eight key genes identified (including Akt).

39
Q

What are some pros of mouse models of diabetes?

A

Similarities in physiology compared to humans; small and easy to maintain; accelerated lifespan; gene editing systems such as CRISPR can be used in mice.

40
Q

What are some cons of mouse models of diabetes?

A

Differences in physiology compared to humans; ethical issues; mice are nocturnal; differences in diet; leptin knockout only deals with a single gene when diabetes is caused by many genes as well as environmental factors.

41
Q

How is insulin held together?

A

By covalent, disulphide bonds between the B and A chains. These bonds are essential for insulin’s structure and make it stable when in the blood.

42
Q

Newly synthesised insulin will only fold and be oxidised in…

A

the lumen of the ER

43
Q

Is proinsulin biologically active?

A

No, it needs the removal of its c-peptide end to become so.

44
Q

Why is co-translational insertion of proteins into the ER common?

A

Its oxidising environment is needed for protein formation

45
Q

Why can cysteine form a disulphide bond?

A

It has an SH sidechain.

46
Q

Where is proinsulin trafficked through before being packaged into secretory granules?

A

The Golgi

47
Q

How are high levels of insulin packaged into secretory vesicles?

A

By making a crystalline complex with Zn2+ ions selectively pumped into the secretory vesicles.

48
Q

What is proinsulin cleaved into?

A

Insulin and C-peptide

49
Q

What is GLUT2?

A

A low affinity glucose transporter expressed in the β-cell plasma membrane. It transports glucose into beta-cells when glucose levels are high.

50
Q

What is Km?

A

Km is the concentration of substrate at which the transporter is working at half of its maximum velocity. It is a measure of affinity - higher Km, lower affinity of transporter for substrate

51
Q

GLUT2 has a linear in proportion response to increase in blood sugar at physiological ranges. This allows phosphorylation of glucose and ATP increases to be proportional to external glucose, allowing β-cell to be a sensor of…

A

glucose concentration

52
Q

The brain expresses GLUT3 which works close to its maximum over the range of physiological blood sugars. Why is there is not a directly proportional increase in rate as blood sugar increases?

A

The brain needs a constant supply of glucose into its cells.

53
Q

What are the key targets of insulin?

A

The muscles, liver and fat

54
Q

What is the structure of the insulin receptor?

A

It is an α2β2 polypeptide which is held together by disulphide bonds.

55
Q

Where is GLUT2 expressed and what kind of affinity does it have?

A

GLUT2 is expressed in beta cells and has a low affinity

56
Q

Where is GLUT3 expressed and what kind of affinity does it have?

A

GLUT3 is expressed in the brain and has a very high affinity

57
Q

Where is GLUT4 expressed?

A

In fat and muscle tissues

58
Q
A

FM, G2E and S2C (3 decks)

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