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Biochem block 2 > Lecture5-PENTOSE PHOSPHATE PATHWAY > Flashcards

Lecture5-PENTOSE PHOSPHATE PATHWAY Flashcards

1
Q

what is the significance or function of Pentose phosphate pathway?

A

-Production of ribose (pentose) sugars for DNA and RNA biosynthesis
-Production of NADPH for an essential reducing equivalent for biosynthesis of fatty acids and sterols (cholesterol, hormones), and for maintenance of reduced glutathione (red blood cells).

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2
Q

What is the net energy produced for PPP?

A

2 NADPH

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3
Q

What is the rate limiting enzyme for PPP?

A

Glucose -6- phosphate dehydrogenase

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4
Q

What is the phase 1 of PPP? oxidative or non oxidative and give me the details of it

A

-Oxidative

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5
Q

What is the phase 2 of PPP? oxidative or non oxidative and give me the details of it

A

Non-oxidative

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6
Q

when is NADPH produced in PPP? what enzyme?

A

phase one–> oxidative phase

Glucose -6- phosphate dehydrogenase

6-phosphogluconate dehydrogenase

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7
Q

Glyceraldehyde 3-phosphate from PPP can be linked to?

A

Glycolysis

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8
Q

Ribose 5 phosphate is used for what?

A

ribose suger in DNA and RNA

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9
Q

The enzyme transketolase is what PPP phase and what is unique about it?

A

Phase 2: non oxidative phase

Needs thiamine and vitamin b1 to function

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10
Q

What is the phase 2 of PPP? oxidative or non oxidative and give me the details of it

A

Non-oxidative

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11
Q

What is fructose 6 phosphate linked to and where is it produced?

A

glycolysis and phase 2

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12
Q

There are two molecules that link to other pathways produced in the PPP, what are they and what pathways

A

Glyceraldehyde 6 phosphate and fructose 6-phosphate

glycolysis

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13
Q

The production of NADPH in PPP is used for what?

A

oxidative stress protection, fatty acid and sterol synthesis

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14
Q

There are how many modes for the production of ribose 5 phosphate, NADPH or ATP?

A

4 modes

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15
Q

What is mode 1 product(s) and what is it for?

A

-produces ribose 5 phosphate
- good for DNA replication

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16
Q

What is mode 2 product(s) and what is it for?

A

Produces 2 NADPH and ribose 5 phosphate

  • good for tumor cells to protect against ROS
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17
Q

What is mode 3 product(s) and what is it for?

A

-Produces 2 NADPH, glyceraldehyde 3 phosphate and dihydroxyacetone phosphate
- Good for ros protection and no ribose 5- phosphate–> RBC

EXTRA
-glyceraldehyde 3 phosphate and dihydroxyacetone phosphate used for glycolysis
- NADPH used for ros protection
- no ribose 5- phosphate

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18
Q

What is mode 4 product(s) and what is it for?

A

-produces 2NADPH, 2ATP and pyruvate for glycolysis
- good for normal cell and ATP production

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19
Q

What is Glutathione?

A

-a tripeptide (glutamate, cysteine and glycine) for protection of cells from oxidative stress

-EX: mitochondria and RBC

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20
Q

How does glutathione protect against oxidative stress?

A

a) Scavenging of peroxide by glutathione peroxidase and
b) regeneration of reduced glutathione by glutathione reductase using NADPH as the reducing agent

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21
Q

What does selenium functions as?

A

functions as a necessary component of enzymes involved in antioxidant protection ( glutathione peroxidase and thioredoxin reductase) and thyroid hormone metabolism

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22
Q

Does selenium react faster or slower with ROSs compared to sulfur in cysteine?

A

faster

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23
Q

Why is selenium faster at reacting with ROSs?

A

The reason for this is that the outer valence electrons of selenium are more loosely held than those of sulfur. As a result, selenium is a better nucleophile and will react with reactive oxygen species faster than sulfur

EXTRA:
But, the resulting lack of π-bond character in the Se-O bond means that the Se-oxide can be much more readily reduced in comparison to S-oxides.

24
Q

What are enzyme is linked diseases linked to PPP? what are the diseases?

A

Glucose-6-phosphate dehydrogenase deficiency–> hemolytic anemia, jaundice and tumors

25
Q

Glucose-6-phosphate dehydrogenase deficiency causes what?

A

Hemolytic anemia and jaundice in the sclera

26
Q

Glucose-6-phosphate dehydrogenase deficiency–> genetics?

A

X-linked recessive hereditary

27
Q

A kid as a Glucose-6-phosphate dehydrogenase deficiency and eats lava beans, what happens? side effects?

A

jaundice in the sclera

Increased chemical and drug sensitivity particularly in children with G6PD deficiencies (e.g. against sulfonamides, aspirin, some antimalarial drugs).

28
Q

Glucose-6-phosphate dehydrogenase deficiency protects against what?

A

malaria

29
Q

What drives DNA synthesis in Tumor cells?

A

Glycolysis

30
Q

In tumor cells what is blocked in the glycolysis?

A

Blocked at the pyruvate kinase step

31
Q

What happens when the pyruvate kinase step is blocked in glycolysis?

A

Glycolysis intermediates are diverted into pentose-phosphate pathway to form ribose sugars for increased DNA synthesis

32
Q

What is the Warburg effect?

A

Increases glycolysis with minimal ATP/energy production

33
Q

In tumor cells, PPP is driving what?

A

increased NADPH production to protect against ROS

34
Q

What is associated with rapidly proliferating tumor cells?

A

Formation of NADPH as protection against ROS

35
Q

what is “hallmarks” of tumor metabolism? (this one is hard, so you can look at slides instead of answering)

A

Increase GLUT1 –> increase glucose uptake (Warburg effect), increase gluconeogenesis of liver

Tumor express embryonic M2-PK pyruvate kinase (lower substrate affinity

Pyruvate kinase is blocked and g-6-p is shifted to PPP for ribose sugars and NADPH

tumors secret lactate which increases LDH—> breakdown of glutamine and alanine to pyruvate as an alt. energy source of TCA cycle resulting in weight loss

36
Q

What causing weight lost in cancer patients

A

tumors secret lactate which increases LDH—> breakdown of glutamine and alanine to pyruvate as an alt. energy source of TCA cycle resulting in weight loss

37
Q

what are the sources of dietary fructose?

A

Sucrose-containing foods and beverages
non diet soft drinks (high fructose corn syrup)

38
Q

What happens when fructose enters the liver/ glycolysis?

A

The phosphofructokinase (RLS) os normal glycolysis is bypassed and goes to F-1-P plus producing ATP.

39
Q

What does aldolase B do?

A

Fructose 1-p –> Glyceraldehyde + Dihydroxyacetone

Glyceraldehyde–> glycolysis

40
Q

A build up of F-1-P can cause what?

A

mental retardation

41
Q

What is hereditary fructose intolerance?

A

-Fructose 1-p cannot go to Glyceraldehyde + Dihydroxyacetone phosphate
- inhibits glycogen phosphorylase (glycogen breakdown)
- results in fructose-induced hypoglycemia

42
Q

What is the treatment of Hereditary Fructose Intolerance ?

A

-Treatment: limit ingestion of fruits, table sugar, and other sweets

43
Q

What is the major source of galactose in human diets?

A

lactose –> milk and milk products

44
Q

Lactose can or cannot be absorbed in the intestine? what is the process?

A

cannot so it needs to be cleaved by lactase enzyme into lactose and glucose

45
Q

What does lactose get cleaved into ?

A

galactose and glucose

46
Q

what is causes non classical galactosemia?

A

-caused by galactokinase deficiency

47
Q

what does non classical galactosemia lead to and how?

A

Cataracts

  • No galactokinase so a build up of galactose which gets turned to galactitol by aldose reductase
48
Q

What causes classical galactosemia ?

A

galactose 1-P accumulates in tissues and galactose so increase of galactose

49
Q

what does classical galactosemia led to and how?

A

cataracts and irreversible mental retardation
no Galactose-1-P uridyltransferase so build up of galactose-1-p so increase galactose

50
Q

how is lactose synthesized?

A
51
Q

besides galactitol, what else can cause cataracts?

A

chronically elevated blood glucose levels in poorly controlled diabetes

52
Q

How do poorly controlled diabetes get cataracts?

A

sorbitol levels increase in the lens of the eye, and can lead to cataract formation.

53
Q

What is galactosemia?

A

is an impairment of galactose metabolism caused by abnormal liver function

54
Q

what is the most common initial clinical symptom of galactosemia?

A

failure to thrive

55
Q

In galactosemia what happens when milk is ingested?

A

Vomiting or diarrhea

jaundice in some

56
Q

Galactosemia causes what within a few days of birth

A

cataracts

57
Q

What is the treatment of Galactosemia?

A

-strictly avoiding all milk and milk-containing products.
- The infant can be fed with soy formula, meat-base formula, or Nutramigen (a protein hydrolysate formula)
- condition is lifelong

Biochem block 2 (10 decks)

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