010 Carbohydrate metabolism 1 Flashcards

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1
Q

Describe the glucose uptake from intestinal lumen into capillaries (with reference to active transport and passive transport)

A

Primary active transport creates a Na+ gradient from inside the enterocyte to the blood vessel. The Na+/K+ ATPase uses energy from hydrolysis of ATP to transport 3 Na+ ions out for every 2K+ ions in the enterocyte. This allows the SGLT1 symporter to transport 2Na+ ions down its concentration gradient from the lumen into the enterocyte, coupled with the entry of a glucose molecule. Once inside the enterocyte, the glucose molecule is passively transported by the GLUT2 channel down its concentration gradient.

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2
Q

What is SGLT1?

A

The Na+/glucose symporter

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3
Q

What is GLUT2

A

Glucose uniporter

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4
Q

Why do transporters and enzymes of glucose differ for different tissues?

A

Different tissues have different glucose requirements

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5
Q

Which glucose receptor is mostly found in the liver and pancreas?

A

GLUT2

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6
Q

Where is GLUT4 mainly found?

A

Muscle, Adipose tissue

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7
Q

Which glucose receptor is mostly found in the brain?

A

GLUT3

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8
Q

Which GLUT receptors have the highest Km and why?

A

GLUT2 as receptors in the digestive tract e.g. pancreas, liver, need to be sensitive to changes in glucose concentrations.

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9
Q

What does a low Km mean physiologically?

A

There only needs to be a low concentration of glucose to saturate the receptors. It works efficiently at low concentrations and keeps a baseline rate of glucose uptake into cell. This guarantees glucose uptake regardless of external concentrations.

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10
Q

What does a high Km mean physiologically?

A

High Km allows more sensitivity to concentration changes to rate of absorption. It takes longer for receptors to be saturated.

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11
Q

Which tissues require a lower Km?

A

Most tissues, including the brain especially.

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12
Q

Which tissues require a higher Km?

A

Pancreas, Liver etc.

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13
Q

How is the reversibility of glucose transport prevented once it enters the tissue?

A

Glucose is carried into the tissue and converted to glucose-6P by hexokinase to prevent it from being transferred back out again.

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14
Q

Which forms of hexokinase is associated with a low Km?

A

Hk I, II, III

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15
Q

Which forms of hexokinase is associated with a high Km?

A

HkIV

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16
Q

Why is it better for glucose to be stored as glycogen?

A

It is insoluble, so when stored in cells it will not draw water in causing cell lysis.

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17
Q

What are the two ways of storing energy?

A

Triglycerides and glycogen

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18
Q

Which form of energy storage is more efficient?

A

Storing energy as triglycerides is more efficient because it is lighter, smaller, and stores much more energy. However it cannot be converted into glucose for the brain.

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19
Q

Describe the structure of glycogen

A

It has a 30nm spherical structure of about 13000 glucose units. Chains are formed by a(1->4) glycosidic linkages and branches off at a(1->6) linkages. There are approximately 8-10 residues per branch point.

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20
Q

Explain the benefits of branching in glycogen molecules

A

Branching increases the attachment points to add or remove glucosyl residues. It makes it more accessible to enzymes that increases solubility. Hence, it increases rate of glucogenesis and glycogenolysis.

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21
Q

Explain the process of glycogenesis

A
  1. Glucose-6P is converted to Glucose-1P by phosphoglucomutas
  2. Glucose 1P is converted to UDP-glucose by UDP -glucose pyrophosphorylase
  3. 8 UDP derived glucose molecules are attached to the autocatalytic glycotransferase primer glycogenin.
  4. Glycogenin remains at the reducing end of the glycogen molecule, as glycogen synthase takes over in glycogen extension. UDP uridine is released.
  5. Branching enzymes attaches 6 residues to non-reducing end of chain.
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22
Q

What is the role of phosphoglucomutas?

A

Phosphoglucomutas catalyzes glucose 6-P to glucose 1-P

23
Q

What enzyme is used as a primer for glycogenesis?

A

glycogenin

24
Q

What is glycogen synthase?

A

Enzyme used to extend the glycogen molecule by attaching more glucosyl residues.

25
Q

Explain the process of glycolysis

A
  1. Glucose is converted into glucose 6P by hexokinase using energy from hydrolyzing ATP.
  2. Fructose 6-P is converted into 1,6 fructose biphosphate by phosphofructokinase using energy from hydrolyzing ATP.
  3. 1,6 fructose biphosphate is converted by aldose to glyceraldehyde 3-P.
  4. Glyceraldehyde 3-P is converted to 1,3 biphosphoglycerade by glyceraldehyde 3-P dehydrogenase using reduction energy of NAD.
  5. Phosphoenolpyruvate is converted to pyruvate by pyruvate kinase.
26
Q

What is the importance of hexokinase?

A

Converting glucose to glucose 6-P to fix it to the cell and prevent it from being transported out again due to reversibility of GLUT transporters.

27
Q

What is the most important regulatory enzyme in glycolysis and why?

A

Phosphofructokinase because this enzyme reflects the concentration of numerous metabolites that reflect metabolic situation of the cell. This has the most effect on glycolysis.

28
Q

If PFK-1 is inactivated, what happens to activity of pyruvate kinase?

A

The decreased production of 1,6 fructose biphosphate will inhibit the action of pyruvate kinase converting phosphoenolpyruvate to pyruvate.

29
Q

Why is the attachment of uridine residues to Glucose 1-P important?

A

There is more binding energy available when binding to both glucose and UDP.

30
Q

What is UDP Glucose pyrophosphorylase?

A

UDP glucose pyrophosphorylase converts glucose 1P to UDP glucose

31
Q

How does the branching enzyme work?

A

For approximately every 7 residues, branching enzyme will attach to the non-reducing side.

32
Q

What does the enzyme pyruvate kinase catalyse?

A

Catalyses phosphoenolpyruvate to form pyruvate

33
Q

What is the glycemic index?

A

The index that measures the effect of ingesting a standard amount of carbohydrate (50g) on blood glucose compared with same amount of glucose.

34
Q

What is the corresponding insulin effect with the glycaemic index?

A

The higher the glycemic index, the higher the insulin effect, showing that some foods that are absorbed can cause a sugar spike.

35
Q

What are some benefits of having a lower GI diet?

A

Lower C-reactive protein
Decrease in glycation of proteins
Reduced LDL and higher HDL
Decreased food intake in subsequent meal

36
Q

Do crystalized starches have high or low glycaemic index? and why?

A

Lower glycaemic index because they are resistant to hydrolization.

37
Q

Why does food processing increase glycaemic indices?

A

It makes starches more available to soluble amylases

38
Q

What are some consequences of having a high GI diet?

A

Constant level of inflammation that is associated with CVD
Increased glycation of proteins
Higher LDL and lower HDL
Glucose spike causes you to eat more in the subsequent meal

39
Q

What dietary changes did the Pima indians experience with what cost?

A

It has been studied that groups that have traditionally used a low GI food as a staple and have recently moved to modern diets, are now experiencing higher rates of diabetes e.g. Pima Indians.

40
Q

What is the glucose tolerance test? How do you use this to determine diabetes and impaired glucose tolerance levels?

A

This tests the response to a glucose load (typically 75g for adult) over a period of time (120mins). Glucose levels must be measured after a 10 hour fast, with no illness or exercise activity. If after 120 minutes a patient has above 11.1mM plasma glucose, they are classified as diabetic. If between 6.1-7.8mM, they are classified with impaired glucose tolerance.

41
Q

How is hyperglycaemia associated with age related diseases e.g. CVD?

A

When glucose levels are high, they non-enzymatically glycate Lys and Val residues which alter protein function. E.g. glycation of apolipoprotin B, altering cholesterol metabolism. The glycated proteins undergo further reaction forming advanced glycation end products (AGE’s) which is involved in the parthenogenesis of many age-related diseases.

42
Q

How does hyperglycaemia affect insulin dependant tissues?

A

In insulin dependant tissues, aldose reductase has a high Km for glucose. At high levels, glucose is converted into sorbitol, which interferes with osmotic pressure in ocular tissue and nerve function in nerve cells.

43
Q

How do you tell if a patient is following insulin medications?

A

Glycation of haemoglobin is irreversible. When you test for glycated haemoglobin, you can identify patients who are missing insulin injection.

44
Q

What is the acceptable physiological range of glycated haemoglobin in a patient?

A

4-6%

45
Q

What is the acceptable physiological range of glycated haemoglobin in a patient?

A

4-6%

46
Q

What is type I diabetes mellitus?

A

Autoimmune destruction of pancreatic B-cells, which destroys the ability to secrete insulin and respond to ingested carbohydrate appropriately.

47
Q

Which genes are affected in type I diabetes?

A

MHC genes

48
Q

What occurs if a type I diabetic patient is not treated with insulin injections?

A

The body is sent into starvation mode and begins to produce glucose and ketone bodies. Patient will develop hyperglycaemia and ketoacidosis.

49
Q

What is type II diabetes?

A

Resistance and impaired insulin secretion. When pancreas must secrete more insulin to provide glucose tolerance, it tires you out and then causes not enough insulin to be released.

50
Q

Name 2 glycogen storage diseases

A

Glycogen synthase deficiency (GSD-0) - poor tolerance of fasting, hypoglycaemia - need for frequent snacking, tiring easily during exercise.
Glycogen branching enzyme deficience (GSD-IV) - accumulation of unbranched, insoluble glycogen chains (polyglucosan), especially in the heart and the liver.

51
Q

What is liver phosphorylase deficiency?

A

When one cannot mobilize liver glycogen and the liver becomes enlarged, mild hypoglycaemia occurs.

52
Q

What is muscle phosphorylase deficiency?

A

When muscles cannot metabolize muscle glycogen, resulting in muscle weakness and poor tolerance of anaerobic exercise.

53
Q

Explain the Warburg effect

A

This states that almost all tumours show an increased rate of glucose uptake and glycolysis. Glycolysis can link with other enzymes to provide substrates for growth.