Hexose Metabolism

Question 1

How does fructose enter the cell?

Answer 1

Glut 5 transporter

Question 2

1. What deficiently leads to fructokinase deficiency?

2. What is the result?

Answer 2

1. Fructose is unable to be converted to fructose 1-phosphate
2. Fructose is excreted in the urine

Question 3

What are some of the results of Hereditary fructose intolerance?

Answer 3

1. Hereditary deficency of hepatic fructose 1- Phosphate aldolase B
2. Build up of F-1-P in the liver and kidney
3. Inhibition of gluconeogenesis and glycogenolysis
4. Depletion of ATP

Question 4

What is the net reaction for galactose metabolism?

Answer 4

Galactose + ATP —-> Glucose 1-P + ADP

Question 5

What enzyme phosphorylates Galactose?

Answer 5

Galactokinase

Question 6

What is the second most common sugar in our diet?

Answer 6

Fructose

Question 7

What transporter does fructose enter on? Where is this located (recall from earlier lecture)

Answer 7

GLUTV, small intestine

Question 8

Describe, briefly, how fructose enters glycolysis.

Answer 8

FructoseF1P via frucokinase  aldolase B produces G3P and DHAP which enters via triose phosphate isomerase

Question 9

What is the major fuel source for sperm?

Answer 9

Fructose (sertoli cells)

Question 10

What is the presentation of fructosuria?

Answer 10

Pretty benign, fructose appears in urine

Question 11

What is the presentation for hereditary fructose intolerance?

Answer 11

Toxic deficiency of aldolase B, f1P is toxic in the liver, vomiting, hypoglycemia, etc. uses up ATP stores and inhibits gluconeogenesis and glycogenolysis

Question 12

How does galactose enter glycolysis?

Answer 12

Galactosegalactose 1 phosphate via galactokinase glucose 1 phosphate via galactose 1 phosphate uridilyl transferase (Leloir pathway) via UDP glucose/galactose exchange

Question 13

What causes classical galactosemia? Nonclassical?

Answer 13

Deficiency of galactose-1-phosphate uridyl transferase; defeiciency of galactokinase

Question 14

What is the presentation of classical galactosemia?

Answer 14

Accumulation of Galactose1P, vomiting, hypoglycemia, lots of other symptoms, galactose in blood and tissues

Question 15

What is the presentation of nonclassical galactosemia?

Answer 15

Galactose in blood and tissues, galactitol accumulates in lens which can lead to cataracts, must avoid galactose in diet completely

Question 16

What is the purpose of the pentose phosphate pathway?

Answer 16

Produce reducing equivalents, ribose phosphates for nucleotide biosynthesis,

Question 17

How many NADPH are made per glucose6phosphate oxidized?

Answer 17

2

Question 18

What stage produces NADPH? Ribose 5 phosphate?

Answer 18

Oxidative, non oxidative stages respectively

Question 19

What is the predominant form of aldolase in liver? Muscle?

Answer 19

B, A, respectively: B is used for glycolytic reasons, A is used for gluconeogenic reasons

Question 20

T or F: aldolase B has a higher affinity for Fructose 1 phosphate than it does for G3P and DHAP.

Answer 20

True

Question 21

What is the rate limiting step for fructose metabolism?

Answer 21

Aldolase B cleavage to G3P and DHAP

Question 22

What pathway synthesizes fructose?

Answer 22

Glucose-polyol pathway

Question 23

Describe the pathway of fructose synthesis

Answer 23

Glucosesoribitol/polyol via aldolase reductasefructose via sorbitol DH

Question 24

Describe the oxidative step for the PPP.

Answer 24

Glucose 6 phosphateto 6 phosphoglucono-delta-lactone with generation of NADPH via glucose 6 DH (NADPH inhibits this step)6 phosphogluconolactone to 6 phosphogluconate via glucolactonase reduced to ribulose 5 phosphate via 6 phosphoglucnate DH (therefore generate 2 NADPH and 1 mol ribulose 5 phosphate)

Question 25

Describe non-oxidative step.

Answer 25

Transketolase takes 2 C fragment from xyulose 5 phosphate (which epiremized from ribose 5 phosphat) and puts it on another ribose 5 phosphate which forms sedoheptulose 7 phosphate and G3P, Sedoheptulose 7P and G3P then form erythrose 4 phosphate and F6P via a transaldolase, eryhthrose 4P then gains another2C fragment from another xyulose 5 phosphate to form F6P and G3P (basically forming 3 glycolytic intermediates)

Question 26

What happens in glucose 6 phosphate dehydrogenase deficiency?

Answer 26

Less NADPHOxidative damage, loss of reducing power to eliminate radicalsprecipitation of Hb in RBC’s cause Heinz bodies and hemolytic anemia

Question 27

Where is fructose mainly metabolized and what is it converted to?

Answer 27

metabolized in the liver and converted to pyruvate under fasting conditions

Question 28

Describe the 2 steps of fructose metabolism

Answer 28

1. Fructose phosphorylated by fructose-1-phosphate | 2. fructose 1-phosphate cleaved by aldolase B to form DHAP and glyceraldehyde => glyceraldehyde 3-phosphate

Question 29

Which intermediate from fructose metabolism will produce pyruvate leading to the TCA cycle

Answer 29

glyceraldhyde 3-phosphate

Question 30

How is fructose produced from glucose?

Answer 30

1. glucose reduced to sorbitol by aldose reductase | 2. Sorbitol reoxidized to form fructose

Question 31

Where would you find fructose derived from glucose? What is the function of fructose in this location?

Answer 31

seminal vesicles and is the major energy source for sperm

Question 32

Describe essential fructosuria and explain the result of the disorder

Answer 32

inherited with accumulation of fructose | fructose is excreted in urine where some may be phosphorylated by HK for glycolysis

Question 33

Describe hereditary fructose intolerance and explain the results of the disorder

Answer 33

hereditary deficiency of hepatic fru-1-P aldolase B leading to an accumulation in liver and kidney -will inhibit gluconeogenesis and glycogenolysis

Question 34

Describe galactose metabolism and energy req.

Answer 34

Galactose + ATP => Galactose 1-P + UDP-glucose => Glucose-1-P + ADP => G-6-P (liver) for glucose in blood

Question 35

Describe classical galactosemia

Answer 35

- deficiency of galactose-1-phosphate uridyl transferase | - accumulation of gal-1-P in tissues and will result in hypoglycemia

Question 36

Describe nonclassical galactosemia

Answer 36

- Deficiency of galactokinase which converts gal => gal-1-P | - results in galactose accumulation in blood and tissue with cataract formation

Question 37

Describe the irreversible oxidative reactions of the pentose phosphate pathway

Answer 37

- 1 carbon of G-6-P is released as CO2; - NADPH is generated; - ribulose 5-phosphate is produced

Question 38

Why are NADPH, ribose 5-phosphate, and pentose sugars formed?

Answer 38

- NADPH: required for reducing equivalents - Ribose 5-phosphate: nucleotide biosynthesis - pentose sugars: rearrange for glycolytic/gluconeogenic intermediates

Question 39

Where does the pentose phosphate pathway occur?

Answer 39

most tissues especially ones that use lots of NADPH

Question 40

Describe the first 2 stages of the pentose phosphate pathway

Answer 40

1st=>oxidative and generates 2 mol of NADPH per -G-6-P oxidized 2nd=>non-oxidative and generates ribose 5-P that is converted unused to intermediates to glycolytic pathway

Question 41

T/F NADPH is a strong inhibitor to G-6-P dehydrogenase

Answer 41

True

Question 42

The NADPH generation will provide what other reactions to occur?

Answer 42

fatty acid synthesis, glutathione reduction (protection against oxidative damage)

Question 43

T/F The cell dictates the direction of the pathway

Answer 43

True

Question 44

Wrt NADPH only, how is the direction of the pathway dictated?

Answer 44

oxidative rxns produce; nonoxidative rxns convert ribose-5-P to G-6-P to produce more NADPH

Question 45

Wrt to ribose 5-P, how is the direction of the pathway dictated?

Answer 45

only nonoxidative rxns as NADPH inhibits G-6-P dehydrogenase so fruc-6-P and glyceraldehyde 3-P and ribose 5-P are produced

Question 46

Wrt to NADPH and pyruvate, how is the direction of the pentose phosphate dictated?

Answer 46

oxidative and nonoxidative rxns are used Nonoxidative=>convert to intermediates to pyruvate via glycolysis

Question 47

Describe the metabolic disorder associated with pentose phosphate shunt along with results

Answer 47

Glucose -6- Phosphate dehydrogenase deficiency Results: more oxidative stress on the cell due to the disulfide bonds being formed bw cysteine residues of 2 GSH molecules