Biochemistry: Fructose And Galactose Oxidation And Pentose Phosphate Pathway

Front 1

What does fructokinase do? Where is it located?

Back 1

Traps fructose as fructose 1 phosphate.

Liver, kidney, intestine.

Front 2

Which two paths can fructose be channeled to?

Back 2

Glycolysis (to pyruvate)
Gluconeogenisis (to glucose)

Front 3

What's the reaction catalyzed by aldolase B?

Back 3

F1P--> Glyceraldehyde + DHAP

Bypasses PFK

*note that Glyceraldehyde phosphate is not phosphorylated. It can be phosphorylated by coupling ATP and ADP by triokinase, to make glyceraldehyde 3PO4.

Front 4

How can excess fructose lead to fatty acid synthesis?

How can excess fructose lead to lactate production?

Back 4

DHAP can be reduced to glycerol phosphate, which is used in fatty acid synthesis (via Acetyl CoA)

Fructose metabolism creates pyruvate faster (more glycolytic intermediates coming in via triose phosphates, and F-1-P stimulates pyruvate kinase) and leads to excess pyruvate production. If TCA gets saturated, lactate can build up. Fructose metabolism is unregulated (bypasses PFK step).

Front 5

What is the defective enzyme in hereditary fructose intolerance?

Pathology? Symptoms? Treatment?

Back 5

Aldolase B --> Fructose 1PO4 builds up, which is hepatotoxic.

Symptoms: Nausea, cirrhosis, hypoglycemia
Treatment: Limit fructose in diet.

Front 6

What is the defective enzyme in fructosuria?

Symptoms? Blood test?

Back 6

Fructokinase

No clinical presentation; elevated blood and urine fructose

Blood tests for fructosuria: Reducing sugars (+) and glucose oxidase (-)

Front 7

How is galactose converted to UDP-glucose in the cell?

Back 7

Galactose ---> galactose 1PO4 (by galactokinase)

Galactose 1-P + UDP-glucose --> UDP-galactose (by GALT, also produces glucose 1-P)

UDP-galactose --> UDP-glucose (by epimerase)

Front 8

What is the enzyme deficiency in Classical Galactosemia?
What builds up?
Symptoms?
What produces cataracts?

Back 8

GALT (Galactose-1-phosphate uridylyltransferase)
Galactose-1P buildup is toxic.
Nausea, avoidance of feeding, mental retardation, and cataracts.
Galactitol produced by the polyol pathway (aldose reductase) produces the cataracts.

Front 9

What are the symptoms of galactosemia from galactokinase deficiency?
Why only cataracts?

Back 9

The kinase is upstream of Galactose-1P, therefore this toxic protein is not built up. Galactose still gets routed into the polyol pathway.

Front 10

What are the steps in the polyol pathway for the synthesis of fructose from glucose?

Back 10

glucose --> sorbitol (uses NADPH --> NADP+)
sorbitol --> fructose (NAD+ -- NADH)

Front 11

What is the metabolic role of the Pentose Phosphate Pathway

Back 11

Supplies NADPH and ribose 5-phosphate, which is present in all cells.

Front 12

What is G6PD "regulated" by?

Back 12

NADP+

NADP+/NADPH= 1/70, therefore, NADP+ is limiting.

Front 13

Which two steps make NADPH in the pentose phosphate pathway?

Back 13

G6P --> 6-Phosphogluconolacetone (by G6PD)

6-Phosphogluconate --> Ribulose 5 Phosphate (also lose CO2)

Front 14

What is NADPH --> NADP+ good for?

Back 14

Gives electrons to oxidized glutathione, making it reduced, and then those electrons get donated to a peroxidase, making 2 H2O. It's good for eliminating free radicals.

Front 15

What's the end metabolite at the end of the oxidative branch of PPP?

Back 15

Ribulose 5 Phosphate
** think, where is this used?

Front 16

What does the oxidative branch only produce?

Back 16

NADPH and Ribulose 5 Phosphate

Front 17

What vitamin does transketolase require?

Back 17

Thiamine

Front 18

What is the non-oxidative branch of PPP?

Back 18

Ribulose 5 Phosphate <-> Xyulose 5 phosphate.

X5P combines with R5P to make Sedoheptulose 7 phosphate and Glyceraldehyde 3 phosphate (using transketolase). Those then combine together to form erythrose 4 phosphate and fructose 6 phosphate (using transaldolase)

E4P then can combine with X5P (using transketolase) to make F6P and Glyceraldehyde 3 phosphate.

Front 19

Which enzyme catalyzes the formation of ribose 5 phosphate? What is its substrate?

Back 19

Pentose phosphate isomerase. Ribulouse 5 phosphate.

Front 20

Which tissues have the greatest pentose phosphate pathway activity?

Back 20

Liver, adipose, adrenal cortex, lactating mammary gland, cornea of eye. NOT in the brain or muscle.

Front 21

How can the pentose phosphate pathway produce ribose only?

Back 21

By using just the non-oxidative branch only.

Front 22

How can the pentose phosphate pathway produce NADPH only?

Back 22

By using both the oxidative branch and the non-oxidative branch. The ribulose-5-PO4 gets converted into F6P and glyceraldehyde-3-PO4

Front 23

How can the pentose phosphate pathway produce both ribose and NADPH?

Back 23

By using the oxidative branch only. (Can't go through the non-oxidative, because it would consumes the ribose)

Front 24

How is glutathione reduced and what is it good for?

Back 24

G6P gives electrons to the PPP, which turns NADP+ --> NADPH
The electrons are then passed to GSSG (glutathione disulfide), which is reduced to glutathione by glutathione reductase.

It is helpful because then, glutathionine peroxidase converts it back to GSSH, it uses a free radical to oxidize it.

Front 25

What is the role of G6P Dehydrogenase deficiency in hemolytic anemia?

Back 25

G6PD facilitates the production of NADPH

Front 26

What does primaquine have to do with hemolytic anemia in G6PDH deficient patients?

Back 26

Primaquine (medication used for malaria sensitivity: Quinones can generate peroxides.

Front 27

What does favism have to do with hemolytic anemia in G6PDH deficient patients?

Back 27

Favism: Fava beans contain oxidant compounds, only G6PD patients are affected. They have hemolytic anemia, and jaundice.

Front 28

What are Heinz bodies?

Back 28

Oxidized hemoglobin. Denatured hemoglobin aggregates, are covalently cross linked.

What does this have to do with hemolysis?

Front 29

What is hemolysis from infection?

Back 29

White blood cells produce H2O2 during infection. G6PD patients have hemolysis.