LESSON 2: AMINO ACIDS AND PEPTIDES

Question 1

First newborn screening test introduced

Answer 1

(early 1960s)

Question 2

PKU

Answer 2

Phenylketonuria

Question 3

Phenylketonuria enzyme deficient

Answer 3

Phenylalanine hydroxylase

Question 4

Phenylalanine is converted to ________ by PAH

Answer 4

Tyrosine

Question 5

phenylalanine metabolites

Answer 5

phenylpyruvic acid,
phenylpyruvate (also known as phenylketone),
and phenyllactic acid

Question 6

Chronically high levels of phenylalanine and some of its metabolites→

Answer 6

brain problems

Question 7

Hyperphenylalaninemia cases that are not the
result of the lack of the PAH enzyme

Answer 7

Deficiency in the enzymes for regeneration and
synthesis of tetrahydrobiopterin (BH4)

Question 8

cofactor for enzymatic hydroxylation of the
aromatic amino acids

Answer 8

BH4

Question 9

aromatic amino acids

Answer 9

phenylalanine,
tyrosine,
tryptophan

Question 10

Phenylalanine levels

Answer 10

> 1,200 μmol/L
Newborn: = 120 μmol/L (2 mg/dL)

Question 11

Phenylketonuria Metabolites Clinical Presentation

Answer 11

blood and urine (characteristic musty odor)

Question 12

Women with PKU (untreated during pregnancy):

Answer 12

microcephalic and mentally retarded babies

Question 13

Phenylketonuria Clinical Presentation

Answer 13

Mental retardation,
failure to walk or talk,
failure of growth,
seizures and tremor
Defect in myelin formation

Question 14

__________ in brain impairs the transport and metabolism of other aromatic amino acids (tryptophan and tyrosine)

Answer 14

phenylalanine

Question 15

Tryptophan synthesis →

Answer 15

serotonin

Question 16

__________ is the pigment synthesized from tyrosine by tyrosinase:

Answer 16

Melanin

Question 17

light skin colour, fair hair, blue eyes

Answer 17

pigmentation hypopigmentation

Question 18

Phenylketonuria Management

Answer 18

Sapropterin dihydrochloride (Kuvan®)
Pegvaliase-PQPZ (Palynziq®)
Dietary Management

Question 19

Reduce phenylalanine levels by increasing the activity of the PAH enzyme

December 2007, the U.S. Food and Drug Administration (FDA): first drug to help manage PKU

Answer 19

Sapropterin dihydrochloride (Kuvan®)

Question 20

Proven to reduce blood Phe levels in adults with PKU: uncontrolled blood Phe levels on existing management

First FDA-approved enzyme substitution therapy as of 2018, substitutes a PEGylated version of the enzyme phenylalanine ammonia lyase for the deficient PAH enzyme

Answer 20

Pegvaliase-PQPZ (Palynziq®)

Question 21

PEGylated

Answer 21

Polyethylene glycol

Question 22

PEGylated MOA

Answer 22

Stealth against the immune system

Question 23

Breakdown of Aspartame

Answer 23

Aspartate
Phenylalanine
Methanol

Question 24

Phenylketonuria Dietary Management

Answer 24

Dietary restriction of phenylalanine with tyrosine supplementation (since phenylalanine is the precursor of tyrosine)

Question 25

Characterized by the excretion of tyrosine and tyrosine catabolites in urine

Answer 25

Tyrosinemia

Question 26

Low levels of the enzyme fumarylacetoacetate hydrolase: last in the series of five

Answer 26

Type I Tyrosinemia

Question 27

Type I Tyrosinemia Clinical Presentation

Answer 27

Failure to thrive, diarrhea vomiting, jaundice, cabbage-like odor, distended abdomen, swelling of legs, increased predisposition for bleeding.

Question 28

Type I Tyrosinemia Organs affected

Answer 28

Leads to liver and kidney failure, problems affecting the nervous system, an increased risk of cirrhosis or liver cancer

Question 29

Type I Tyrosinemia Management

Answer 29

Nitisinone (also known as NTBC) Diet

Question 30

Potent reversible inhibitor of 4-hydoxyphenlypyruvate deoxygenase

Answer 30

Nitisinone (also known as NTBC)

Question 31

Type I Tyrosinemia Diet

Answer 31

prescribed a low-phenylalanine, low tyrosine diet

Question 32

AKA Richner-Hanhart syndrome deficiency of the enzyme tyrosine aminotransferase: first in the series

Answer 32

Type II Tyrosinemia

Question 33

Type II Tyrosinemia Clinical Presentation

Answer 33

Mentally retarded Excessive tearing, photophobia (abnormal sensitivity to light), eye pain and redness, painful skin lesions on the palms and soles of the feet.

Question 34

Type II Tyrosinemia Symptomatic Management

Answer 34

Limit certain amino acids, such as phenylalanine and tyrosine Dietary restriction of tyrosine, phenylalanine and methionine (avoid milk and dairy products, meat, fish chicken, eggs, beans and nuts is recommended) Keratolytics and emollients for hyperkeratotic skin lesions Oral retinoids for persistent keratoderma.

Question 35

Rare disorder (only a few cases have been reported) Deficiency of the enzyme 4- hydroxyphenylpyruvate dioxygenase: second of the series of five

Answer 35

Type III Tyrosinemia

Question 36

Type III Tyrosinemia Clinical Presentation

Answer 36

Mild mental retardation, seizures, and periodic loss of balance and coordination

Question 37

Type III Tyrosinemia Management

Answer 37

Follow a phenylalanine- and tyrosine-restricted diet

Question 38

Defective enzyme: homogentisate oxidase in tyrosine metabolism

Answer 38

Alkaptonuria

Question 39

➢Homogentisate (on standing):

Answer 39

oxidized by polyphenol oxidase → benzoquinone acetate → polymerization → pigment called alkapton (black or brown)

Question 40

urine of alkaptonuric patients resembles _________ in color

Answer 40

coke

Question 41

Alkaptonuria Clinical Presentation

Answer 41

Ochronosis Arthritis Signs of aortic or mitral valvulitis

Question 42

Alkaptonuria Management

Answer 42

➢Ascorbic Acid ➢ Nitisinone

Question 43

Absence or greatly reduced activity of the enzyme branched-chain α-ketoacid dehydrogenase → blocking normal metabolism of leucine, isoleucine, and valine

Answer 43

Maple Syrup Urine Disease (MSUD)

Question 44

Valine →

Answer 44

propionyl CoA

Question 45

Isoleucine →

Answer 45

propionyl CoA and acetyl CoA

Question 46

Leucine →

Answer 46

acetoacetate and acetyl CoA

Question 47

Maple Syrup Urine Disease (MSUD) Clinical Presentation

Answer 47

Characteristic maple syrup or burnt sugar odor Accumulation of the branched chain amino acids and corresponding ketoacids Neurological complications in babies

Question 48

Pathophysiology valine

Answer 48

alpha-ketoisovalerate

Question 49

Pathophysiology isoleucine

Answer 49

alpha -keto-β-methylvalerate

Question 50

Pathophysiology leucine

Answer 50

alpha-ketoisocaproate

Question 51

Maple Syrup Urine Disease (MSUD) Management

Answer 51

Thiamine -> Essential coenzyme in carbohydrate and amino acid metabolism. Dietary restriction of branched-chain AA

Question 52

Defective transport of cystine and basic amino acids across renal tubule and the small intestine. Autosomal-recessive defect involving the gene that codes for cystine transporter known as SLC3A1 (SLC for solute carrier)

Answer 52

Cystinuria

Question 53

Cystinuria amino acids:

Answer 53

cystine ornithine, lysine, and arginine

Question 54

Cystinuria Clinical Presentation

Answer 54

Formation of cystine stones in the kidney, Chronic urinary tract infections Hematuria and dysuria

Question 55

Cystinuria Management

Answer 55

Hydration Urinary Alkalinizers Chelating Agents Crystal Growth Inhibitors

Question 56

Unbranched chain of amino acids - peptide bond

Answer 56

Peptides

Question 57

Long unbranched chain of amino acids - peptide bond

Answer 57

Polypeptides

Question 58

Molecular weights ranging from about 6000 to about 40,000,000.

Answer 58

Proteins

Question 59

Molecular weight of less than about 5000

Answer 59

Polypeptides

Question 60

Oligopeptide (10-20 aa)

Answer 60

Peptides

Question 61

antidiuretic hormone, Nonapeptide

Answer 61

Vasopressin

Question 62

Enhances contraction of smooth muscle cells: wall of the uterus, Stimulates milk ejection from the mammary glands via mechanical stimulus, Nonapeptide

Answer 62

Oxytocin

Question 63

Synthetic oxytocin

Answer 63

Pitocin

Question 64

Binds to receptor sites to reduce pain body’s natural painkillers; Produced by the brain, Pentapetide

Answer 64

Enkephalins

Question 65

Action of narcotic analgesics such as __________ and __________ is based on their binding at the same receptor sites in the brain

Answer 65

morphine; codeine

Question 66

Enkephalins Role

Answer 66

memory and learning, control of body temperature, sexual activity, and mental illness

Question 67

Regulator of oxidation–reduction reactions, protect cellular contents from oxidizing agents, Glu–Cys–Gly (tripeptide)

Answer 67

Glutathione

Question 68

Highly reactive forms of oxygen

Answer 68

peroxides and superoxides