Chapter 12: Glycolysis and Pyruvate Dehydrogenase (continued)

Question 1

What are the 2 places where galactose is metabolized?

Answer 1

in brain and liver mainly

Question 2

What are the 2 most important enzymes to remember in galactose metabolism and lead to galactosemia with deficiency of these enzymes?

Answer 2

galactokinase and galactose 1-phosphate uridyltransferase

Question 3

How is cataracts caused in those with galactosemia?

Answer 3

result when there is conversion of excess galactose in peripheral blood to galactitol in the lens of they eye, which has aldose reductase

accumulation of galactitiol in the lens causes osmotic damage and cataracts

Question 4

Hallmark sign of galactosemia?

Answer 4

cataracts

Question 5

MOA for why diabetics also get cataracts?

Answer 5

same mechanism as that in galactosemia,

because aldose reductase also converts glucose to sorbitol which causes osmotic damage

Question 6

Why is deficiency of galactose 1- phosphate uridyltransferase more severe than galactokinase deficiency?

Answer 6

because galactose 1-P accumulates in the liver, brain, and other tissues

Question 7

Inheritance pattern of galactosemia?

Answer 7

AR

Question 8

What is primary lactose intolerance caused by?

Answer 8

hereditary deficiency of lactase

Question 9

What is secondary lactase deficiency caused by?

Answer 9

any age by GI disturbances such as celiac sprue, colitis, or viral-induced damage to intestinal mucosa

Question 10

What are the symptoms of lactase deficiency caused by?

Answer 10

attributed to bacterial fermentation of lactose to a mixture of CH4, H2, and small organic acids. The acids are osmotically acitve and result in the movement of water into the intesitinal lumen

Question 11

How do you diagnose lactose intolerance?

Answer 11

positive H breath test after an oral lactose load

Question 12

How do you treat lactose intolerance?

Answer 12

dietary restriction of milk and milk products (except unpasteruized yogurt, which contains active lactobacillus or by lactase pills

Question 13

How do you diagnose galactosemia?

Answer 13

newborn screening heel prick test

Question 14

What is the treatment for newborns diagnosed with galactosemia in the first few weeks of life?

Answer 14

formulas containing galactose free carbs are given

Question 15

Draw out metabolism of fructose.

Answer 15

Draw out diagram

Question 16

Fructokinase deficiency symptoms? How is one usually diagnosed?

Answer 16

some dehydration and dumping of sugar in urine but otherwise benign

usually detected incidentally when urine is checked for glucose with a dipstick

Question 17

Aldolase B def symptoms?

Answer 17

• lethargy, vomiting
• liver damage, hyperbilirubinemia
• hypoglycemia
• hyperuricemia, lactic acidosis
• renal proximal tubule defect (Fanconi)

Question 18

Another name for aldolase B deficiency?

Answer 18

fructose 1-P aldolase activity deficiency

Question 19

What is the biochemical reason why a high-fructose drink supplies a quick source of energy in both aerobic and anaerobic cells?

Answer 19

because DHAP and glyceraldehyde are downstream from the key regulatory and rate limiting enzyme PFK-1

Question 20

What is fructose found in?

Answer 20

honey and fruit

Question 21

What are important enzymes to remember in the metabolism of fructose?

Answer 21

fructokinase and fructose 1-P aldolase (aldolase B)

Question 22

Where are the 2 places fructose is commonly metabolized?

Answer 22

in the liver and renal proximal tubules

Question 23

Why does fructose accumulation in the body not cause cataracts?

Answer 23

because it is not an aldose sugar. and therefore not a substrate for aldose reductase in the lens

Question 24

Inheritance pattern for hereditary fructose intolerance?

Answer 24

AR

Question 25

PDH in the liver is activated by insulin, does this hold true for PDH in the brain and nerves?

Answer 25

no; the enzyme (actually, a complex of 5 enzymatic activities) is not responsive to hormones in these locations

Question 26

What are the cofactors and coenzymes used by PDH?

Answer 26

Tender Love and Care for Nancy

• thiamine pyrophosphate (TPP) from the vitamin thiamine
• Lipoic acid
• Coenzyme A (CoA) from pantothenate
• FAD (H2) from riboflavin
• NAD (H) from niacin (some may be synthesized from tryptophan)

Question 27

What product of metabolism is PDH inhibited by?

Answer 27

acetyl-CoA

Question 28

Draw out the path for glycolysis focusing on PDH and products.

Answer 28

Draw out diagram

Question 29

Compare and contrast Wernicke and Korsakoff?

Answer 29

Wernicke = peripheral neuropathy
Korsakoff = psychosis

Question 30

Wet beri beri major symptom?

Answer 30

congestive heart failure

Question 31

Why is CHF caused in wet beri-beri?

Answer 31

owing to inadequate ATP and accumulation of ketoacids in the cardiac muscle

Question 32

What are other enzymes (complexes?) besides PDH that utilize thiamine?

Answer 32

• a-ketoglutarate dehydrogenase (citric acid cycle)
• Branched chain ketoacid dehydrogenase (metabolism of branched-chain amino acids)
• transketolase

Question 33

What is the treatment if thiamine deficiency is suspected in an individual?

Answer 33

give IV thiamine prior to glucose (dextrose) admin (to prevent lactic acidosis)

Question 34

Thiamine deficiency significantly impairs oxidation of what?

Answer 34

glucose oxidation

Question 35

How does thiamine deficiency and the enzymes that require thiamine affect brain, cardiac muscle and muscle?

Answer 35

it impairs glucose oxidation so highly aerobic tissues like brain and cardiac muscle fail first.

in addition, branched chain amino acids are sources of energy in brain and muscle