Chapter 12: Glycolysis and Pyruvate Dehydrogenase (continued) Flashcards
What are the 2 places where galactose is metabolized?
in brain and liver mainly
What are the 2 most important enzymes to remember in galactose metabolism and lead to galactosemia with deficiency of these enzymes?
galactokinase and galactose 1-phosphate uridyltransferase
How is cataracts caused in those with galactosemia?
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
Hallmark sign of galactosemia?
cataracts
MOA for why diabetics also get cataracts?
same mechanism as that in galactosemia,
because aldose reductase also converts glucose to sorbitol which causes osmotic damage
Why is deficiency of galactose 1- phosphate uridyltransferase more severe than galactokinase deficiency?
because galactose 1-P accumulates in the liver, brain, and other tissues
Inheritance pattern of galactosemia?
AR
What is primary lactose intolerance caused by?
hereditary deficiency of lactase
What is secondary lactase deficiency caused by?
any age by GI disturbances such as celiac sprue, colitis, or viral-induced damage to intestinal mucosa
What are the symptoms of lactase deficiency caused by?
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
How do you diagnose lactose intolerance?
positive H breath test after an oral lactose load
How do you treat lactose intolerance?
dietary restriction of milk and milk products (except unpasteruized yogurt, which contains active lactobacillus or by lactase pills
How do you diagnose galactosemia?
newborn screening heel prick test
What is the treatment for newborns diagnosed with galactosemia in the first few weeks of life?
formulas containing galactose free carbs are given
Draw out metabolism of fructose.
Draw out diagram
Fructokinase deficiency symptoms? How is one usually diagnosed?
some dehydration and dumping of sugar in urine but otherwise benign
usually detected incidentally when urine is checked for glucose with a dipstick
Aldolase B def symptoms?
- lethargy, vomiting
- liver damage, hyperbilirubinemia
- hypoglycemia
- hyperuricemia, lactic acidosis
- renal proximal tubule defect (Fanconi)
Another name for aldolase B deficiency?
fructose 1-P aldolase activity deficiency
What is the biochemical reason why a high-fructose drink supplies a quick source of energy in both aerobic and anaerobic cells?
because DHAP and glyceraldehyde are downstream from the key regulatory and rate limiting enzyme PFK-1
What is fructose found in?
honey and fruit
What are important enzymes to remember in the metabolism of fructose?
fructokinase and fructose 1-P aldolase (aldolase B)
Where are the 2 places fructose is commonly metabolized?
in the liver and renal proximal tubules
Why does fructose accumulation in the body not cause cataracts?
because it is not an aldose sugar. and therefore not a substrate for aldose reductase in the lens
Inheritance pattern for hereditary fructose intolerance?
AR
PDH in the liver is activated by insulin, does this hold true for PDH in the brain and nerves?
no; the enzyme (actually, a complex of 5 enzymatic activities) is not responsive to hormones in these locations
What are the cofactors and coenzymes used by PDH?
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)
What product of metabolism is PDH inhibited by?
acetyl-CoA
Draw out the path for glycolysis focusing on PDH and products.
Draw out diagram
Compare and contrast Wernicke and Korsakoff?
Wernicke = peripheral neuropathy
Korsakoff = psychosis
Wet beri beri major symptom?
congestive heart failure
Why is CHF caused in wet beri-beri?
owing to inadequate ATP and accumulation of ketoacids in the cardiac muscle
What are other enzymes (complexes?) besides PDH that utilize thiamine?
- a-ketoglutarate dehydrogenase (citric acid cycle)
- Branched chain ketoacid dehydrogenase (metabolism of branched-chain amino acids)
- transketolase
What is the treatment if thiamine deficiency is suspected in an individual?
give IV thiamine prior to glucose (dextrose) admin (to prevent lactic acidosis)
Thiamine deficiency significantly impairs oxidation of what?
glucose oxidation
How does thiamine deficiency and the enzymes that require thiamine affect brain, cardiac muscle and muscle?
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
