Biochem - Metabolism (Amino Acid Derivatives & Associated Disorders)

Question 1

Draw the derivatives of phenylalanine in consecutive order, including the cofactors required to create them.

Answer 1

See p. 110 in First Aid 2014 for visual at top of page

Question 2

Draw the derivatives of Tryptophan in consecutive order, including the cofactors required to create them.

Answer 2

See p. 110 in First Aid 2014 for visual at top of page

Question 3

What substance is a derivative of Histidine? What cofactor is required for its synthesis?

Answer 3

Histamine; B6

Question 4

What important substance is a derivative of Histidine? What cofactor is required in their synthesis?

Answer 4

Porphyrin => Heme; B6

Question 5

What are 2 important derivatives of glutamate? Which requires B6 cofactor for its synthesis?

Answer 5

GABA, Glutathione; B6 for GABA synthesis

Question 6

What are 3 important derivatives of arginine? Which of these requires BH4 cofactor for its synthesis?

Answer 6

Creatine, Urea, Nitric oxide; BH4 for Nitric oxide synthesis

Question 7

What enzyme is affected in Alkaptonuria? What is the normal function of this enzyme?

Answer 7

Homogentisate oxidase: Homogentisic acid => Maleylacetoacetic acid; Note: Homogentistic acid is derived from Tyrosine (which is dervied from Phenylalanine) and Maleylacetoacetic acid feeds into the TCA cycle

Question 8

What enzyme is affected in PKU? What is the normal function of this enzyme?

Answer 8

Phenylalanine hydroxylase: Phenylalanine => Tyrosine (using BH4 as cofactor)

Question 9

What enzyme is affected in Albinism? What is the normal function of this enzyme?

Answer 9

Tyrosinase; DOPA (dihydroxyphenylalanine) => Melanine

Question 10

What enzyme is inhibited by Carbidopa? What is the normal function of this enzyme?

Answer 10

DOPA decarboxylase: DOPA (dihydroxyphenylalanine) => Dopamine (using vitamin B6 as cofactor)

Question 11

What factor in the catecholamine synthesis/tyrosine catabolism pathway is stimulated by cortisol? What effect does this have?

Answer 11

SAM (S-adenosylmethionine): Norepinephrine => Epinephrine

Question 12

Draw the major products of the phenylalanine/tyrosine catabolism/catecholamine synthesis pathway.

Answer 12

See p. 110 in First Aid 2014 for visual near bottom of page

Question 13

What are 2 causes of phenylketonuria? Which of these causes malignant PKU?

Answer 13

Due to decreased phenylalanine hydroxylase or decreased tetrahdrobiopterin cofactor (malignant PKU).

Question 14

What amino acid becomes essential in patients with PKU?

Answer 14

Tyrosine becomes essential

Question 15

What urine finding is associated with PKU, and what causes this?

Answer 15

Increased phenylalanine leads to excess phenylketones in urine

Question 16

What are 6 clinical findings associated with phenylketonuria?

Answer 16

Findings: (1) Intellectual disability (2) Growth retardation (3) Seizures (4) Fair skin (5) Eczema (6) Musty body odor; Think: “disorder of AROMAtic amino acid metabolism => musty body ODOR”

Question 17

What is the treatment of phenylketonuria?

Answer 17

Treatment: Low phenylalanine and High tyrosine in diet

Question 18

What is of most concern with maternal PKU?

Answer 18

Lack of proper dietary therapy during PKU

Question 19

What are 4 clinical findings in an infant affected by maternal PKU?

Answer 19

Findings in infant: (1) microcephaly (2) intellectual disability (3) growth retardation (4) congenital heart defects

Question 20

What is the mode of inheritance of PKU? What is its incidence?

Answer 20

Autosomal recessive. Incidence ~ 1:10,000

Question 21

When is PUK screened for, and why?

Answer 21

Screened for 2-3 days after birth (normal at birth because of maternal enzyme during fetal life)

Question 22

What are 3 examples of phenylketones?

Answer 22

Phenylketones - (1) Phenylacetate, (2) Phenyllactate, and (3) Phenylpyruvate

Question 23

What substance must PKU patients avoid, and why?

Answer 23

PKU patients must avoid the artificial sweetener aspartame, which contains phenylalanine

Question 24

What is another name for Alkaptonuria?

Answer 24

Alkaptonuria (ochronosis)

Question 25

What is Alkaptonuria (ochronosis)?

Answer 25

Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate

Question 26

What is the mode of inheritance of Alkaptonuria? Is it a benign or malignant disease?

Answer 26

Autosomal recessive. Benign disease.

Question 27

What are 4 clinical findings associated with Alkaptonuria?

Answer 27

Findings: (1) dark connective tissue, (2) brown pigmented sclerae, (3) urine turns black on prolonged exposure to air. May have (5) debilitating arthralgias (homogentisic acid toxic to cartilage).

Question 28

What musculoskeletal finding may be present in patients in Alkaptonuria, and why?

Answer 28

May have debilitating arthralgias (homogentisic acid toxic to cartilage).

Question 29

What is the mode of inheritance of all types of homocystinuria?

Answer 29

All autosomal recessive

Question 30

What are 3 forms of homocystinuria? What do all forms have in common?

Answer 30

Types (all autosomal recessive): (1) Cystathionine synthase deficiency (2) Decreased affinity of cystathionine synthase for pyridoxal phosphate (3) Homocysteine methyltransferase (methionine synthase) deficiency; All forms result in excess homocysteine

Question 31

What is the treatment for homocystinuria due to cystathionine synthase deficiency?

Answer 31

Treatment: low methionine, high cysteine, high B12 and folate in diet

Question 32

What is the treatment for homocystinuria due to low affinity of cystathionine synthase for pyridoxal phosphate?

Answer 32

Treatment: very high B6 and high cysteine in diet

Question 33

What is the treatment for homocystinuria due to homocysteine methyltransferase (methionine synthase) deficiency?

Answer 33

Treatment: High methionine in diet

Question 34

What are 8 clinical findings associated with homocystinuria?

Answer 34

Findings: (1) very high homocysteine in urine (2) intellectual disability (3) osteoporosis (4) tall stature (5) kyphosis (6) lens subluxation (downward and inward) (7) thrombosis and (8) atherosclerosis (stroke and MI)

Question 35

What ophthalmologic condition is associated with homocystinuria?

Answer 35

Lens subluxation (downward and inward)

Question 36

What vascular condition is associated with homocystinuria? What are 2 complications that may arise?

Answer 36

Atherosclerosis (stroke and MI)

Question 37

Draw the important reactions related to homocysteinuria, highlighting the 2 enzymes that may be affected to cause this disorder.

Answer 37

See p. 111 in First Aid 2014 for visual near bottom of page

Question 38

What is the defect in cystinuria?

Answer 38

Hereditary defect in renal PCT and intestinal amino acid transporter for Cysteine, Ornithine, Lysine, and Arginine; Think: "COLA"

Question 39

What urine finding occurs in cystinuria, and why?

Answer 39

Excess cysteine in urine can lead to precipitation of hexagonal cystine stones

Question 40

What is the mode of inheritance of cystinuria? What is its incidence like?

Answer 40

Autosomal recessive. Common (1:7000)

Question 41

What test is diagnostic for cystinuria?

Answer 41

Urinary cyanide-nitroprusside test

Question 42

What is the treatment for cystinuria?

Answer 42

Treatment: urinary alkalinization (e.g., potassium citrate, acetazolamide) and chelating agents increase solubility of cystine stones; good hydration

Question 43

Of what is cystine composed?

Answer 43

Cystine is made of 2 cysteines connected by a disulfide bond

Question 44

What is the defect and metabolic effects of maple syrup urine disease?

Answer 44

Blocked degradation of branched amino acids (Isoleucine, Leucine, Valine) due to decreased alpha-ketoacid dehydrogenase (B1). Causes increased alpha-ketoacids in the blood, especially those of leucine; Think: "I Love Vermont MAPLE SYRUP from maple trees (with BRANCHES)"

Question 45

What are 3 symptoms/conditions caused by maple syrup urine disease?

Answer 45

Causes severe CNS defects, intellectual disability, and death

Question 46

What is the mode of inheritance of maple syrup urine disease?

Answer 46

Autosomal recessive

Question 47

What describes the urine of patients with maple syrup urine disease?

Answer 47

Urine smells like maple syrup/burnt sugar

Question 48

What is the treatment for maple syrup urine disease?

Answer 48

Treatment: restriction of leucine, isoleucine, and valine in diet, and thiamine supplementation