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GI > Hexose Monophospahte Pathway > Flashcards

Hexose Monophospahte Pathway Flashcards

1
Q

The Hexose Monophosphate Pathway (HMP) begins with

A

Glucose-6-Phosphate

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2
Q

HMP’s principal purpose is the production of the cell’s basic anabolic reducing power, reduced

A

NADPH

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3
Q

The secondary purpose of the HMP is the synthesis of

A

Ribose-5-Phosphate (R5P)

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4
Q

Seven, six, five and four carbon compounds are

A

HMP intermediates

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5
Q

These sugar intermediates can enter the pathway directly from the diet, as well via G6P and by salvage of pentoses produced by catabolism of cellular constituents such as

A

Nucleotides and Glucuronic Acid

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6
Q

Likewise, these intermediates may be siphoned off for other biosynthetic purposes. Their principal fate is as precursors in

A

Glycolysis

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7
Q

The primary mechanism for the regulation of this pathway involves the cell’s need for

A

NADPH

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8
Q

The primary mechanism for the regulation of this pathway involves the cell’s need for NADPH, exerting its effect upon the first enzyme in the pathway

A

G-6-P Dehydrogenase

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9
Q

Takes place in the cytoplasm of all cell types

A

HMP

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10
Q

Because there are alternative routes for R5P synthesis, most pathology associated with defects in this pathway are attributable to a diminished supply of

A

Reducing Power (NADPH)

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11
Q

What are the two phases to the HMP?

A
  1. ) Oxidative Phase

2. ) Non-oxidative (sugar-interconversion) phase

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12
Q

Neither phase utilizes

A

ATP

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13
Q

There are three irreversible steps in the oxidative phase, followed by the isomerization of ribulose 5-phosphate to

A

Ribose-5-Phosphate

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14
Q

It is the #1 carbon of G6P that is recovered as

A

CO2

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15
Q

Unless the cell requires R5P as precursor for other specific biosynthetic processes it is further metabolized by a series of sugar interconversions, ultimately producing precursors for glycolysis in the

A

Non-oxidative phase

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16
Q

The reactions catalyzed in the nonoxidative phase are all

A

Reversible

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17
Q

In the non-oxidative phase, Ribulose 5-P is isomerized to produce ribose 5-P, and it is also epimerized to produce

A

Xylulose 5-P

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18
Q

After three additional reactions, first with a transketolase, then a transaldolase, and concluding with again with transketolase, we arrive at

A

Glycolysis intermediates

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19
Q

Which two glycolysis intermediates does the non-oxidative phase produce?

A

Glyceraldehyde-3-phosphate and fructose-6-phosphate

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20
Q

The starting material for the HMP is

A

3 moles of G-6-P

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21
Q

What are the 4 end products of the HMP?

A
  1. ) 3 CO2
  2. ) 6 NADPH
  3. ) 2 F-6-P
  4. ) 1 Glyceraldehyde-3-P
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22
Q

When the cell needs more NADPH than it does R-5-P, we use the glyceraldehyde and F-6-P products to synthesize

A

G-6-P

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23
Q

This G-6-P can be used to produce how many NADPH

A

12

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24
Q

This is a likely scenario in cells where there is a considerable need for NADPH, such as in the synthesis of

A

Fatty Acids

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25
Q

When the cell needs equal amounts of NADPH and R-5-P, what happens?

A

HMP “halts” with conclusion of oxidative phase

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26
Q

In this scenario, no sugar interconversions occur because R5P is utilized in other processes before it can be acted on by

A

Transketolase

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27
Q

This might commonly occur in rapidly dividing cells with the need to replicate the genomic material

A

Needing more R-5-P than NADPH

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28
Q

Because the sugar-interconversion reactions are reversible, it is possible to synthesize R5P from

A

Glycolytic Intermediates

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29
Q

What happens when the cell requires more NADPH than it does R5P but does not have the luxury of performing gluconeogenesis (I.e. the cell needs more ATP)?

A

In this case the sugar-interconversion phase fully converts R5P to glycolytic precursors

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30
Q

Sometimes, the cell needs more NADPH than it does R-5-P but it can not undergo gluconeogenesis. In this case the sugar-interconversion phase fully converts R5P to glycolytic precursors which then act as substrate in the

A

TCA cycle

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31
Q

This occurs via pyruvate, with the concamitant synthesis of

A

2 moles ATP per mole of acetyl-CoA

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32
Q

The rate limiting step in the HMP is the first one, catalyzed by

A

Glucose-6-phosphate Dehydrogenase (G6PDH)

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33
Q

G6PDH is, in the short term, principally regulated in a negative feedback manner by

A

NADPH

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34
Q

Long term regulation occurs at the level of transcription of the gene encoding G6PDH, and is influenced positively by

A

Insulin

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35
Q

The cell’s principal currency in anabolic reducing power

A

NADPH

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36
Q

Its synthesis is the basis for our dietary requirement for

A

Niacin/Nicotinamide

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37
Q

Able to donate TWO so-called reducing equivalents

A

NADPH

38
Q

In contrast to NADH, made during glycolysis and the TCA cycle and used in the process of oxidative phosphorylation, NADPH is NOT associated with

A

Oxidative Phosphorylation or ATP synthesis

39
Q

Required in several phases of fatty acid synthesis

A

NADPH

40
Q

Production of the major product of fatty acid synthesis, palmitate, a 16 carbon fatty acid requires

A

14 molecules of NADPH

41
Q

Required at two different points in the process of cholesterol biosynthesis

A

NADPH

42
Q

The synthesis of mevalonate from 3-hydroxy-3-methylglutaryl CoA requires

A

2 NADPH

43
Q

Hydroxylation of cholesterol to certain steroid hormones also requires NADPH, in a process involving the

A

P-450 System

44
Q

Conversion of the ribose unit of nucleotides to the deoxyribose form is a multi-step process that begins with

A

NADPH

45
Q

Ribose is converted to deoxyribose by the enzyme

A

Ribonucleotide reductase

46
Q

NADPH is also required for the conversion of

A

dUMP to dTMP

47
Q

Over 100 isozymes are members of this “superfamily” of mono-oxygenases with specificities for the oxidation of steroids, carcinogens, drugs or xenobiotic substances

A

Cytochrome P-450 enzymes

48
Q

The aim of the P-450 system is to recognize, solubilize and thereby promote the removal of such foreign materials from the body via

A

The Kidneys

49
Q

A variety of chemical transformations are possible among the array of P-450 enzymes, but they all have in common the reaction of a single oxygen with either a

A

Carbon, Sulfur, or Nitrogen

50
Q

What is NADPH’s role in the P-450 system?

A

Reduces iron from Fe3+ to Fe2+ at two points in the cycle

51
Q

Reducing power is transferred to the cytochrome by an intermediary called the

-a membrane bound enzyme

A

NADPH-Cytochrome P-450 reductase

52
Q

The P-450 system functions best with substrates with some

A

Hydrophobicity

53
Q

In addition to functioning in drug and xenobiotic removal, specific P-450 enzymes are used in the biosynthesis of

A

Steroid Hormones

54
Q

Catalyzes a reaction from cigarette smoke that is actually dangerous to humans

A

P-450 system

55
Q

The chemical process by which granulocytes (macrophages, neutrophils and eosinophils) destroy invading microorganisms is initiated by

A

NADPH oxidase

56
Q

Forms superoxide form NADPH and O2

A

NADPH oxidase

57
Q

NADPH oxidase forms superoxide (a free-radical form of oxygen) from NADPH and O2 with the consumption of O2. This is referred to as a

A

Respiratory Burst

58
Q

Converts superoxide to hydrogen peroxide

A

Superoxide dismutase

59
Q

Genetic defects in the NADPH oxidase leads to

-Reduces the hosts ability to fight bacterial infections

A

Granulomatous Disease

60
Q

A tripeptide present in high concentrations in all cell types and functions to protect cellular components from the reactive peroxides

A

Glutathione

61
Q

Reduced glutathione (GSH) reacts with peroxide to form

A

Water

62
Q

Regeneration of GSH requires NADPH and the enzyme

A

Glutathione reductase

63
Q

Catalyzes the conversion of arginine and O2 to citruline and NO, requiring one NADPH in the process

A

NO-synthetase

64
Q

This pathway possibly accounts for a considerable portion of the body’s use of

A

NADPH

65
Q

One of the precursors in the biosynthesis of aromatic amino acids

A

Erythrose 4-phosphate

66
Q

A prosthetic group in the transketolase functioning in the non-oxidative phase of the HMP

A

Thiamine Pyrophosphate (TPP)

67
Q

Covalently bound to the two carbon unit that is exchanged in the transketolase reaction

A

TPP

68
Q

Transketolase that lacks TPP is

A

Inactive

69
Q

Individuals harboring mutations in transketolase that reduce its affinity for TPP can display a series of symptoms that are in aggregate referred to as the

A

Wernicke-Korsakoff Syndrome (WKS)

70
Q

In large part, the symptomology is neurological, ranging from depression, irritability and fatigue to

A

Confusion, ataxia, and opthalmoplegia

71
Q

Most commonly seen in chronic alcoholics, presumably due to poor absorption of the vitamin

A

Wernicke-Korsakoff Syndrome (WKS)

72
Q

Represents the most prevalent enzymopathy in human populations, where as many as 400 million people world wide are deficient

A

G6PDH Deficiency

73
Q

10-25% of tropical African populations, 1-3% of some Mediterranean populations, and 5-10% of tropical and sub-tropical Asian populations are affected by

A

G6pDH deficiency

74
Q

Defects in transketolase do not have an immediate influence upon the production of

A

NADPH

75
Q

However, defects in G6PDH drastically affect the production of

A

NADPH

76
Q

G6PDH deficiency presents as a form of

A

Hemolytic anemia

77
Q

Can be induced by the ingestion of the fava bean

A

G6PDH

78
Q

Deficiency for G6PDH in red blood cells (RBC) severely restricts its ability to generate

A

NADPH

79
Q

When ROS build up in RBCs they can react with hemoglobin, which results in the precipitation of

A

Heinz bodies

80
Q

The G6PDH gene is located on the

A

X-chromosome

81
Q

An example of a class IV enzyme; it shows an alteration in electrophoretic mobility, but no significant difference in its enzymatic properties

A

G6PDH A variant

82
Q

More severe, and do show clinical symptoms, albeit rarely and under specific circumstances

A

Class III mutations

83
Q

A member of class III mutations

A

G6PDH A- varient

84
Q

Higher up on the scale of severity is the G6PD Mediterranean, categorized in

A

Class II

85
Q

The Mediterranean variant shows normal enzyme activity, but is present in much reduced levels in the

A

RBC

86
Q

Lastly, class I mutations are the most severe, with chronic anemia. These most severe deficiencies in G6PDH activity have a condition called

A

Nonspherocytic anemia

87
Q

There is a link between the presence of mutations in G6PDH and resistance to

A

Malaria

88
Q

Ironically, individuals with G6PDH deficiency may show the characteristic hemolytic response to the anti-malarial drug

A

Primaquine

89
Q

In lipid synthesizing cells of the adipose, mammary gland and liver as much as 70% of the NADPH produced comes from the so-called

-The reason G6PDH deficiency does not always show severe symptoms

A

Malic Enzyme

90
Q

NADPH can also be produced from NADH in the mitochondrion, by means of

A

Nicotinamide Nucleotide Transhydrogenase

GI (59 decks)

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