Carbohydrate Metabolism 3_Molecules Flashcards Preview

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Flashcards in Carbohydrate Metabolism 3_Molecules Deck (82):
1

What does major pathway for fructose metabolism do?

Bypasses major regulatory reaction in glycolysis

2

How long does it take for fructose to be absorbed from the intestine compared to glucose?

Fructose is less rapidly absorbed from the intestine than is glucose, but once in the blood, it is more rapidly metabolised

3

How is fructose phosphorylated to glycolytic intermediate fructose - 6- phosphate?

By Hexokinase

4

Why is the reaction from fructose to fructose-6-phosphate known as a minor pathway?

the pathway is important only when the fructose concentration is very high because the Km of hexokinase is more than 3mmol/L

5

If the conversion to fructose - 6- phosphate is a minor pathway what is most of the dietary fructose phosphorylated by?

Most of the dietary fructose is phosphorylated by fructokinase in liver, kidneys and intestines

6

Which (kidney, liver, intestine) account for almost half of the total fructose metabolism?

Liver

7

What does fructokinase do that is different from hexokinase?

Fructokinase produces fructose-1-phosphate which is not a glycolytic intermediate.

8

What happens after fructokinase produce fructose-1-phosphate?

F-1-P is cleaved to dihydroxyacetone phosphate and glyceraldehyde by aldolase B, an isoenzyme of aldolase that can cleave both F-1,6-biphosphate and F-1-P. The products are then metabolised by glycolysis or gluconeogenesis.

9

What happens after fructokinase produce fructose-1-phosphate?

F-1-P is cleaved to dihydroxyacetone phosphate and glyceraldehyde by aldolase B, an isoenzyme of aldolase that can cleave both F-1,6-biphosphate and F-1-P. The products are then metabolised by glycolysis or gluconeogenesis.

10

What happens during fructose metabolism in the liver, kidney and small intestine

- 2 ATP is consumed as for glucose
- Liver metabolises fructose to Fru-1-P more rapidly than glucose
- Build up of Fru-1-P after a high sucrose meal can deplete cellular phosphate

11

What happens when you deplete cellular phosphate?

1) impaired oxidative phosphorylation, ATP production
2) Potential liver damage

12

What is the enzyme deficiencies associated with fructose metabolism?

1) Fructokinase deficiency
2) Aldolase B deficiency

13

What is the Fructokinase deficiency?

Benign
High levels of fructose in blood and urine
Fructose levels such that hexokinase metabolises it to Fructose-6-P

14

What is Aldolase B deficiency?

Hereditary fructose intolerance
Build up of Fructose-1-P
Depletion of phosphate and ATP

15

What does Aldolase B deficiency cause?

Liver damage/failure/death

16

How do you treat Aldolase B deficiency?

Sucrose and fructose free diet

17

How many ATP is used for Galactose metabolism?

1 ATP used - same as for glucose to glc-6-P

18

What happens in galactose metabolism?

Galactose feeds into other pathways that use Glc-6-P, Glc-1-P and UDP-Gal

19

When does conversion of galactose to galacticol occurs when?

Only at very high galactose levels with the enzyme aldose reductase present

20

Why does fructose-1-phosphate tend to accumulate?

Liver metabolises fructose faster than glucose and because the activity of fructokinase exceeds that of aldolase B in the liver

21

What is the relationship between fructose and glucose in the liver?

Fructose promotes glucose metabolism in the liver

22

How does fructose-1-phosphate stimulate glucokinase?

By binding to the glucokinase regulating protein.

23

What does fructose-1-phosphate stimulate?

Glucokinase and inactive phosphorylated form of glycogen synthase but has no effect on PFK.

24

What can cause galactosemia?

1) Deficiency of galactokinase
2) Deficiency of uridyltransferase

25

What type of disease is the galactosemia caused by deficiency of galactokinase?

Mild disease, with elevated levels of galactose in blood and urine

26

What happens when you have a deficiency of galactokinase?

Production of galactiol

27

What does production of galactiol lead to?

Cataract formation

28

What type of disease is the galactosemia caused by deficiency of uridyltransferase?

Common Galactosemia, with accumulation up of Gal-1-P and galactiol

29

What is affected when there is a deficiency of uridyltransferase?

Depletion of cellular phosphate and ATP - tissue damage
wide range of tissues affected
liver damage
mental retardation
cataract

30

What is a treatment of deficiency of uridyltransferase?

Removal of lactose from diet (newborn screening NB)

31

What is polyol pathway?

Physiological pathway for alludes reductase

32

Where is the polyol pathway active in?

In seminal fluid where fructose is the major energy source for sperm cells
Active in lens, retina, blood vessels and peripheral nerves

33

What important products does the pentose phosphate pathway?

1 ribose-5-phosphate
2 NADPH

34

What is other name for pentose phosphate pathway?

Hexose monophosphate shunt

35

What is the ribose-5-phosphate produced by the pentose phosphate pathway used for?

Precursor for the synthesis of purine and pyrimidine nucleotides

36

What is the NADPH produced by the pentose phosphate pathway used for?

1) for reduction reactions in anabolic pathways (NADPH is a redox coenzyme) AND
2) for protection against oxidative pathways

37

What is pentose phosphate pathway for?

Major pathway of glucose metabolism in:
1) Rapidly dividing cells
2) Cells that synthesise fatty acids, cholesterol, steroids,
3) Cells exposed to high oxygen concentrations e.g. rbis, cornea

38

What is the major product produced in rapidly dividing cells?

Ribose-5-P

39

What is the major product produced in the cells that synthesise fatty acids, cholesterol, steroids?

NADPH

40

What is the major product produced in cells exposed to high oxygen concentrations e.g. rbis, cornea?

NADPH

41

Which branch of the pentose phosphate pathway synthesise NADPH?

oxidative branch

42

What does Glucose-6-phosphate dehydrogenase do?

catalyse the committed and rate limiting step

43

Having the glucose-6-phosphate dehydrogenase reaction be irreversible does what?

Enables the cell to maintain a high [NADPH]/[NADP+] ratio.

44

Why do cells use NADPH rather than NADH whenever a strong reducing agent is required?

Cells generally contain far more NADPH than NADP+ this is in contrast to NADH whose concentration is generally far lower than the NAD+ concentration.

45

What is the rate limiting step of the pentose phosphate pathway?

Step 1, catalysed by Glu-6-P dehydrogenase

46

What is the rate of the pentose phosphate pathway determined by?

By availability of NADP+

47

When is NADPH a major pathway of pentose phosphate pathway?

1) RBC: protection against oxidative damage
2) Adipose tissue: Fat synthesis
3) Liver: Fat synthesis
4) Testes, Ovaries: Steroid synthesis
5) Adrenals: Steroid synthesis
6) Mammary Tissue: Fat synthesis

48

What happens to Ribose-5-phosphate after production?

Recycled into the glycolysis pathway: non-oxidative phase

49

What does the non oxidative brach of the pentose phosphate pathway do?

links ribulose-5-phosphate, the product of the oxidative branch, to glycolysis and gluconeogenesis.

50

What is the purpose of the non-oxidative phase of the pentose phosphate pathway?

To convert 5-C products of oxidative phase to glycolysis substrates: 2 x Fructose-6-P and Glyceraldehyde-3-P (GAP)

51

What are the most important enzymes in this reversible reaction sequence (non-oxidative phase)

Transketolase
Transaldolase

52

What does transketolase do?

Transfers a two carbon unit

53

Transaldolase

Transfers a three carbon unit

54

What does transketolase contain that transaldolase contain?

Enzyme bound thiamin pyrophosphate, which functions as a transient carrier of the two carbon unit.

55

What happens when the cell needs more ribose-5-phosphate than NADPH?

Ribose-5-phosphate is formed not only through the oxidative branch but also by reversal of the reactions in the non oxidative branch

56

What happens when the cell needs more NADPH than ribose-5-phosphate?

Oxidative and non oxidative branches work in series to form fructose-6-phosphate and glyceraldehyde-3-phosphate.
These products are recycled to glucose-6-phosphate in the gluconeogenic reaction. In this mode, the whole glucose molecules can be oxidised to CO2 and NADPH

57

How does NADPH protect cells from oxidative damage?

By maintaining the tripeptide glutathione in the reduced stage
Antioxidant protect the cell (major cellular antioxidant: glutathione)

58

What is a consequence of oxidative metabolism?

Production of damaging reactive oxygen species (OH-, O2-, H2O2)

59

What is used to replenish reduced glutathione (GSH)?

NADPH

60

What is the sole source of NADPH in red blood cells and cornea?

Pentose Phosphate Pathway

61

What causes drug-induced haemolytic anaemia?

Genetic deficiency in Glu-6-P dehydrogenase (reduced enzyme activity)

62

When does drug-induced haemolytic anaemia arise?

Only when affected individuals exposed to increased levels of oxidative stress

63

When can cause you to get increased levels of oxidative stress?

1) Oxidant drugs e.g. primaquine (antimalarial); chloramphenicol (broad-spectrum antibiotic)
2) Infection
3) Eating broad beans (favism)

64

What causes RBC to haemolyse?

Red blood cells cannot produce sufficient NADPH to protect against oxidative damage

65

Name the complex carbohydrates

1) Glycosaminoglycans
2) Glycoproteins
3) Glycolipids

66

How does synthesises of GAGs work?

1) Core proteins synthesised on rough ER into ER lumen
2) Glycosylated by membrane-bound transferases as it moves through the ER, Golgi
3) Monosaccharides added one by one to the growing polysaccharide chain
4) Sulfation/iduronate synthesis then takes place before the next monosaccharide is added
5) Extruded to extracellular space

67

How does synthesis of glycoproteins work?

Branched oligosaccharides linked to protein via either:
- O-linkages to serine or threonine residues
- N-linkages to asparagine

68

What is lysosomal enzymes?

Glycoproteins

69

What happens during lysosomal targeting?

1) During glycosylation in Golgi 'tagged' with Mannose-6-P
2) Man-6-P 'tag' directs the glycoprotein to the lysosome

70

What is I-cell disease?

Rare, recessively inherited disease in which one of the enzymes for the attachment of mannose-6-phosphate (on glycoproteins) to prospective lysosomal enzyme is deficient.

71

What happens during I-cell disease?

1) Lysosomal enzymes are not sorted into the lysosomes but are secreted into plasma (wrongly 'addressed')
2) High levels of lysosomal enzymes circulate in the blood and undegraded lipids and polysaccharides accumulate in the cells ("I" = inclusion bodies)

72

What does the accumulation of the products from I-cell disease lead to?

1) Mental deterioration
2) Skeletal deformities
3) Death between 5 - 8 years of age

73

What happens during degradation?

- GAS and Glycoproteins digested in lysosomes
- Oligosaccharide chains digested sequentially by specific acid hydrolyses - 'last on, first off'

74

What happens when there is a deficiency of any one of the acid hydrolyses?

Causes acid degradation to stop with accumulation of the remaining oligosaccharide chain

75

What are the two types of lysosomal storage disease?

1) Mucopolysaccharidoses
2) Oligosaccharidoses

76

What is Mucopolysaccharidoses?

Diseases resulting in the accumulation of GAG fragments (accumulation of specific oligosaccharide)

77

What is Oligosaccharidoses?

Diseases resulting from teh accumulation of branched oligosaccharides from glycoproteins (or glycolipids)

78

What does Mucopolysaccharidoses cause?

1) Causes cell death and tissue damage
2) Progressive diseases - normal at birth
3) many organs affected, wide range of severity
4) Mental deficiency and physical deformity common

79

What does the pentose phosphate pathway account for?

1) Significant portion of the total glucose oxidation in tissue with active fatty acid or cholesterol synthesis including liver, adipose tissue, adrenal cortex, lactating mammary gland
2) important in cells that are exposed to high oxygen partial pressure

80

What does NAPD from pentose phosphate pathway do?

Protect cells from oxidative damage by maintaining the tripeptide glutathione in the reduced state. When glutathione acts as a reducing agent, it forms a disulphide bond with a second glutathione molecule. (reduced form of glutathione is an antioxidant)

81

When does the amount of glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase increased in?

in well fed state and this effect probably is mediated by insulin

82

In the short term, glucose-6-phosphate dehydrogenase is inhibited by?

a high [NADPH]/[NADP+} ratio. Therefore increased NADPH consumption increase activity of the oxidative branch