2-25-16-Genetic Disorders Of Metabolic Pathways (Seidler) Flashcards Preview

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Flashcards in 2-25-16-Genetic Disorders Of Metabolic Pathways (Seidler) Deck (31)
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1
Q

Defects in the biosynthesis or regeneration of ___ can lead to secondary phenylketonuria

A

THB

2
Q

The pathways for the production of monoamine neurotransmitters (dopamine, norepi, and serotonin) from Tyr and Trp are disrupted when ___ is deficient, leading to neurologic dysfunction

A

THB

3
Q

___ is used in the treatment of secondary PKU

A

Synthetic THB (Sapropterin)

4
Q

Defects in the activity of ___ causes phenylketonuria (PKU), the most common inborn error of AA metabolism. Phe in these patients is converted to ___ and then to phenylacetate

A

Phenylalanine hydroxylase

Phenylpyruvate

5
Q

In ___, a pts urine may have a musty odor and the synthesis of melanin is impaired due to decreased production of Tyr

A

Phenylketonuria

6
Q

Consequences of excess phenylalanine leads to inhibition of:

___ enzyme–> leads to decrease in pigmentation

___ enzyme –> decrease in serotonin synthesis

___ enzyme –> decrease in GABA synthesis and possible decrease in all catecholamines

A

Tyrosinase

5HT decarboxylase

Glutamate decarboxylase

7
Q

What are 2 lab tests for measuring phenylalanine levels?

A

Guthrie test-bacterial inhibition assay

Mass tandem spectrophotometry (MS/MS)

8
Q

___ is characterized by phenylalanine crossing the placenta and PAH in the fetal liver is unable to convert Phe to Tyr

A

Maternal PKU

9
Q

___ is due to a defect in homogentisate oxidase, an enzyme in the Tyr degradative pathway

A

Alkaptonuria

10
Q

In alkaptonuria, autooxidation of homogentisic acid (with light) and polymerization of products produces ___ in urine

A

Dark-colored pigments

Black pigmentation in the IV disks of patients with degenerative arthritis and ochronosis (darkened sclera) are also observed

11
Q

___ is an autosomal recessive disorder that typically presents in 20’s-30’s with discoloration of sclera (ochronosis) and dark-colored urine. There is an accumulation of homogentisic acid and severe degeneration of cartilage of spine and major joints as well as kidney disease is observed

A

Alkaptonuria

12
Q

___ is an essential cofactor in the hydroxylations of the aromatic AA’s Phe, Tyr, and Trp, as well as in the production of NO from Arg. It is biosynthesized from GTP via a pathway involving 3 enzymes and is regenerated by the reduced form of NADPH-dependent reduction of DHB catalyzed by dihydropteridine reductase.

A

THB

13
Q

___ is an autosomal recessive disease due to a severe lack of melanin. It results in partial or complete absence of normal pigment in skin, hair, and eyes.

A

Albinism

14
Q

In albinism, the conversion of tyrosine to melanin is blocked due to defects in the enzyme ___

A

Tyrosinase

15
Q

This type of tyrosinemia is the most common and infants will have cabbage-like odor and possible liver failure

A

Type I tyrosinemia

16
Q

Infants with tyrosinemia type I will excrete a lot of ___ in the urine due to the build up of fumarylacetoacetate

A

Succinylacetone

17
Q

Hereditary infantile tyrosinemia (tyrosinemia type I) is the result of a defect in the gene encoding __ enzyme

A

Fumarylacetoacetate hydrolase

Converts fumarylacetoacetate to acetoacetate/fumarate

18
Q

List the defective enzymes in the following disorders:

Phenylketonuria-____

Albinism- ___

Alkaptonuria- ___

Tyrosinemia type I- ___

A

Phenylketonuria-Phenylalanine hydroxylase

Albinism-Tyrosinase

Alkaptonuria-Homogentisate oxidase

Tyrosinemia Type I-Fumarylacetoacetate hydrolase

19
Q

What is the front-line treatment for tyrosinemia type I?

A

Nitisinone–> reversible inhibitor of para-hydroxyphenylpyruvate oxidase. It prevents the formation of fumarylacetoacetate, which is the precursor for the toxic succinylacetone

20
Q

___ result from defective metabolism of homocysteine due to vitamin deficiencies (B6, B12, and folic acid) or due to inherited defects in enzymes such as cystathionine beta synthase

A

Hyperhomocysteinemia and homocystinuria

21
Q

DVT, stroke, atherosclerosis, marfan-like habitus, MR, and joint contractures are all clinical features of ___

A

Homocystinuria

22
Q

__ is an autosomal recessive disease in which symptoms appear 3-4 days after birth including feeding difficulties, vomiting, lethargy, progressive neurodegeneration, abnormal muscle tone, coma, and death. There is an elevation in urine and plasma BCAA’s and alpha keto acids, as well as a burnt sugar smell in urine

A

Maple syrup urine disease

23
Q

Which AAs are of interest in maple syrup urine disease?

A

Valine, Isoleucine, and Leucine–> All BCAAs

24
Q

A defect in ___ enzyme is characteristic of maple syrup urine disease

A

Branched-chain Alpha-ketoacid decarboxylase (dehydrogenase in blue box)

25
Q

In some forms of mild Maple syrup urine disease, the acivity of branched chain alpha keto acid dehydrogenase may be restored to normal by __ supplementation of the diet

A

Thiamine (B1)

26
Q

Vitamin B1 is AKA ___

Vitamin B5 is AKA ___

Vitamin B2 is AKA ___

Vitamin B3 is AKA ___

A

TPP (thiamine, B1)

Coenzyme A (Pantothenate, B5)

Flavin adenine dinucleotide (FAD; riboflavin, B2)

Nicotinamide adenine dinuceotide (NAD+; Niacin, B3)

27
Q

___ galactosemia occurs when the conversion of galactose to glucose-1-phosphate is prevented due to galactose-1-phosphate uridyl transferase deficiency

A

Classic

28
Q

___ galactosemia occurs when the conversion of galactose to galactose-1-phosphate is prevented due to a defect in galactokinase

A

Nonclassic

29
Q

List the enzyme deficiency in:

Nonclassic galactosemia- ___

Classic galactosemia- ____

A

Galactokinase

Galactose-1-P- uridyl transferase

30
Q

In galactosemia, ___ deposition in the eye leads to cataracts in early infancy

A

Galactitol

31
Q

___ is when infants are unable to utilize galactose found in milk. Infants suffer from malnutrition and failure to thrive. There is damage to the liver, brain, eyes in first few days and may develop MR

A

Galactosemia