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Fundamentals of Molecular Medicine > HMP Shunt Pathway > Flashcards

HMP Shunt Pathway Flashcards

1
Q

What is the overall point of the HMP Shunt Pathway?

A

Alternate Pathway for Glucose Metabolism

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2
Q

Roles of HMP Shunt Pathway

A
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3
Q

What Pathway will require 5 carbon Sugars

glycolysis?

glycogen storage

fatty acid synthesis

RNA synthesis

TCA Cycle

A

RNA synthesis — we can make the 5 carbon sugars needed for RNA (and DNA?)

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4
Q

Oxidative vs. Non-Oxidative Pathways

A
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5
Q

Transketolase vs. Transaldolase

A
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6
Q

Transaldolase requires

A

a lysine in the active site.

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7
Q

Which other enzyme requires thiamin as a cofactor?

Pyruvate kinase

Pyruvate dehydrogenase

Isocitrate dehydrogenase

Aldolase

Aminoacylt tRNA

Alpha KG Dehydrogenase

A

Pyruvate dehydrogenase

Alpha KG Dehydrogenase

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8
Q

Review of Thiamine Deficiency

A
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9
Q

The Oxidative Steps of HMP

A
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10
Q

Epimerization and Isomerization of Ru5P

A
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11
Q

What other reaction pathway contains a similar Epimerization reaction?

Glycolysis

Fructose Metabolism

Galactose Metabolism

TCA Cycle

Mitochondrial Shunts

A

Galactose Metabolism — C4 Epimerase

TCA Cycle — Isomerase but not epimerization

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12
Q

First Transketolase Reaction

A
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13
Q

First TransALDOLASE Reaction

A
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14
Q

What happens to the E4P produced?

A
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15
Q

Regulation of the HMP Shunt Pathway

A
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16
Q

Which pathway requires NADPH?

Glycolysis

Gluconeogenesis

Xenobiotic Detoxification

Fatty Acid oxidation

TCA Cycle

Ox. Phos.

A

Xenobiotic Detoxification — Cytochrome System requires NADPH

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17
Q

What are the 3 types of Cells?

A
  1. Cells require more R5P than NADPH
  2. Cells that need equal amounts of R5P than NADPH
  3. Cells require NADPH but not R5P
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18
Q

Cells that require more R5P than NADPH

A
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19
Q

Cells that Need Equal Amounts of NADPH and R5P

A
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20
Q

Cells that Require NADPH, but not R5P

A
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21
Q

Rationale behind the different Pathways

A
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22
Q

Cells that need NADPH and Carbons for Biosynthesis

A
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23
Q

Overview of the Metabolism

A
24
Q

Summary of Directions of the HMP Pathway

A
25
Q

Biochemical Consequences of G6PDH Deficiency

A
26
Q

Symptoms of People with G6PDH Deficiency

A

Soldiers got the following symptoms:

Scleral Icterus

Jaundice

Hemolytic Anemia

Mediterranean descent

Mutation on X-Chromosome that was G6P

They were aysomptomatic until they received drugs at home. Drugs are oxidizing agents which triggered the disorder.

RBC’s are primarily affected. Remember RBC’s have no mitochondria.

THE RBC use transhydrogenase as their only means of generating NADPH

27
Q

Consequences of G6PDH Deficiency Continued

A
28
Q

Glutathione Pathway

A
29
Q

G6PDH Deficiency Defined

A
30
Q

G6PDH Resistance to Malaria

A
31
Q

Sickle Cell Carrier Resistance to Malaria

A
32
Q

Overview of Eythrocyte Metabolism

A

Erythrocyte has pathways that some other cells don’t.

Upper Right Branch of the pathway is dependent on NADP concentration.

Iron atom in center of heme binds oxygen but it can only bind…… not the ferric state.

Methemoglobin gets converted back to the hemoglobin by met reductase.

Whenever we go through the 2,3 BPG shunt we’re by passing the generation of an ATP.

33
Q

Reactive Oxygen Species

A
34
Q

Which organelle would you expect to exhibit the most damage from ROS?

Lysosome

Mitochondria

Golgi Apparatus

Endoplasmic reticulum

Nucleus

A

Mitochondria

35
Q

Enzymes which use Molecular Oxygen

A
36
Q

Cytochrome P450 Family

A
37
Q

More on Cytochrome P450

A
38
Q

Tylenol Toxicity

A
39
Q

Radical Damage and Chain Terminators

A
40
Q

Anti-Oxidant Enzymes

A
41
Q

A major role of the HMP shunt pathway is?

Generate ATP

Generate NADH

Generate FADH

Bypass PFK1

Provide cofactor for anabolic pathways

Providing cofactor for catabolic pathways

A

Provide cofactor for anabolic pathways

42
Q

Production of glucose from ribose 5-phsophate in the liver would require which one of the following enzymes?

Pyruvate carboxylase

pyruvate dehydrogenase

PEP Carboxykinase

G3P DH

Fructose 1,6 Bisphosphatatse

A

Fructose 1,6 Bisphosphatatse

43
Q

Level of oxidative damage is 10 times greater than nuclear DNA Why?

Superoxide dismutase is present in the mitochondria

Nucleus lacks glutathione

Nuclear membrane presents a barrier to ROS

Mitochondrial membrane is permeable to ROS

Mitochondria DNA Lacks Histones

A

Mitochondria DNA Lacks Histones — So it’s not protected from ROS

44
Q
A

G6PDH Deficiency?

45
Q

Chronic Alcoholic has nystagmus, inability to balance, easily confused. Which enzyme assay would likely demonstrate a reduction of activity?

A

Alphaketoglutarate dehydrogenase — only enzyme listed that requires Thamine

46
Q

See Above. Assay of which of the following enzymes can determine a biochemical reason for these symptoms?

Isocitrate DH

Transaldolase

Transketolase

G3PDH

G6pDH

A

Transketolase

47
Q

New born gets treated with thiamin to alleviate symptoms of lactic acidosis lethargy and poor muscle tone. Why is the treatment successful?

Such treatment allows the mutated enzyme to produce NADPH

The mutated enzyme has a reduced Km for thiamine

The mutated enzyme has an increased Km for thiamine

Such treatment allows cells to produce 5 carbon sugars which are necessary for cell division

A

The mutated enzyme has an increased Km for thiamine (I.e. Reduced Affinity)

48
Q

The conversion of Ribose 5 Phosphate to free glucose in liver requires?

G6PDH

Pyruvate Kinase

Malate Dehydrogenase

Aldolase

G3PDH

A

Aldolase

49
Q

American american male had fave beans he was fatigued and shows anemia. What is the likely defect?

NADH

NAD

Reduced Glutathione

Oxidized Glutathione

Cystine

Homocystine

A

Reduced Glutathione

50
Q

Glutamic Acid can be converted into alpha KG in one step which enzyme below is required for the alpha ketoglutarated to be covered to free glucose?

Citrate Synthase

PFK1

Pyruvate Kinase

Pyruvate Carboxylase

Aldolase

A

Aldolase — you need aldolase to make Fructose 1,6 BP

51
Q

Individual of mediterranean descent develops hemolytic anemia can still generate 5 carbon sugars from glucose requiring the participation of which of the following enzymes below?

G6PDH

G3PDH

PFK1

Pyruvate Kinase

F1,6BP

A

PFK1

52
Q

A drug developed to inhibit PEP carboxykinase would not block gluconeogenesis from which substrate?

Aspartate

Lactate

Glutamate

Glycerol

Succinyl CoA

A

Glycerol

53
Q

New born exhibits hypoglycemia during periods of fasting. Enzyme assays reveal a defective phoshoglucomutase. This led to reduced glucose production from which on e of the following?

Glycogen

F6P

Glycerol

Lactate

Aspartate

G6P

A

Glycogen — only one requires phosphoglucomutase

54
Q

AN individual inherited a mutation in the gen for the UDP Glucose pyrophosphorylase such that it is 95% inactive? This is the consequence of which disorder?

Inability to use either galactose or glycogen as an energy source

Inability to make glycogen from any sugar or to utilize galactose as an energy source.

A

Inability to make glycogen from any sugar or to utilize galactose as an energy source.

55
Q

Individual has a mutation of UDPGLucose Epimerase. What is the likely consequence of this disorder?

A

Inability to use galactose as an energy source with no effect on the ability to use glycogen

Fundamentals of Molecular Medicine (77 decks)

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