EXAM3_L35_Metabolic_Diseases

Question 1

Inheritance pattern is a good clue to what the deficiency is

RECESSIVE:rr
DOMINANT:Rr, RR

Answer 1

Recessive: ENZYMES or peptide hormones

Dominant: Structural or non-enzymatic PROTEINS

Question 2

Pathology of Enzymatic disorders are attributed to what two things?

Answer 2

BUILDUP of Reactants or
DEFICIENCY of Products or

Combination of both

Question 3

MACROMOLECULAR diseases vs small molecule diseases

Answer 3

Macromolecular diseases are confined to the tissues where the substrate accumulates (ie mucopolysaccharide)

Small molecular diseases are unpredictable b/c they can move freely throughout body and damage cells they normally don’t come in contact with

Question 4

Biochemical steps affected in Aldolase B deficiency
what two problems?
what two effects?

Answer 4

HYPOGLYCEMIA*

1. accumulation of Fructose 1-Phosphate
2. Decreased Pi levels (tied to F1P)
   - decreases liver glycogenolysis
   - decreases ATP synthesis

Question 5

Aldolase B deficiency lowers Pi levels, what does this affect?

Answer 5

Decreases glycogenolysis

-because Pi is the substrate for glycogen phosphorylase

Question 6

Aldolase B deficiency lowers Pi levels causing decreased glycogenolysis and also lowers ATP. What affect does the low ATP have on the cell?

Answer 6

Decreased gluconeogenesis due to low levels of ATP

Question 7

Jaundice is also seen in aldolase b deficiency- what is this indicative of?

Answer 7

Liver damage and failure

Question 8

What is the remedy for Aldolase b deficiency?

Answer 8

DONT EAT FRUCTOSE, SUCROSE, or SORBITOL

Question 9

Why are Cataracts not a feature of aldolase b deficiency?

Answer 9

Fructose is a KETOSE (not an aldose sugar)

• Aldose reductase cannot convert fructose to galactitol (which causes cataracts)

Question 10

Pi (inorganic phosphate) levels decrease in aldolase b deficiency. What is Pi a substrate for?

Answer 10

Glycogen phosphorylase (needed in glycogenolysis)

Question 11

Why is it justified to perform population screening of newborns for galactosemia? “PKU screening”

Answer 11

• Causes:
• severe mental retardation (often fatal)
• Gi, cirrhosis, cataracts

Even when recognized- learning disabilities are common

Question 12

Gal-1-P Uridyltransferase deficiency

Answer 12

Buildup of GALACTOSE
-buildup of Glactose 1-Phosphate

aldose reductase (high km for galactose) but in high galactose > converted to GALACTITOL

CATARACTS, MENTAL RETARDATION

Question 13

What converts Galactose to galactitol?

Answer 13

aldose reductase (only works on aldose sugars)
usually no signs without dietary galactose intake
- only when buildup of Galactose will it convert to galactitol b/c it has such a high km for galactose.

Question 14

Andersen/Type IV GSD

Answer 14

No Branching Enzyme

• long glycogen branches causes Immune response
• Liver Cirrhosis- death by 5yo.

Question 15

Hers/Type VI GSD

Answer 15

deficient Glycogen Phosphorylase (Liver)

• Severe hepatomegaly due to buildup of glycogen
• Hypoglycemia or sometimes no symptoms

Question 16

McArdle/Type V GSD

Answer 16

deficient Glycogen phosphorylase (Muscle)

-exercise induced cramps/intolerance

Question 17

Cori/Type III GSD

Answer 17

deficien De Branching enzyme

• hepatomegaly
• Fasting hypoglycemia (no glycogenolysis)
• Myopathy

Question 18

Von Gierke/Type I GSD

Answer 18

Deficient Glucose 6 Phosphatase

• lethargy
• seizures
• hepatomegaly

Question 19

Type 1, 2, 3, 4,5,6 Glycogen Storage Disorders and their deficiency

“Vacation paradise comes after more hell”

Answer 19

1- VonGierke- G6Pase (seizures, lethargy)
2-Pompe- Lysosomal alpha glucosidase (heart failure)
3- Cori- deBranching (fasting hypoglycemia)
4- Andersen- Branching (cirrhosis)
5- McArdle- Muscle Glycogen phosphorylase (cramps)
6- Hers- Liver Glycogen Phosphorylase (hypoglycemia)

Question 20

Pompe/TypeII GSD & LSD

Answer 20

Deficient in Lysosomal alpha-glucosidase
-heart muscle dysfunction
death by 2yo

Question 21

Accumulation of Fructose 1 -P

Answer 21

Aldolase B deficiency (hereditary fructose intolerance)

Question 22

Accumulation of Glactose-1-P

Answer 22

Hepatic Gal-1-P-uridyltransferase (galactosemia)