Inborn Errors of Metabolism

Question 1

What are the different forms of IEM?

Answer 1

Carbohydrate disorders, Fatty acid oxidation defects, Aminoacidopathies

Question 2

What are examples of carbohydrate disorders?

Answer 2

Galactosemia, fructosemia

Question 3

What are some examples of fatty acid oxidation defects?

Answer 3

Medium chain acyl-CoA, dehydrogenase deficiency.

Question 4

What are some examples of aminoacidopathies?

Answer 4

Phenylketonuria, Alkaptonuria

Question 5

What are oligosaccharides?

Answer 5

Two or more monosaccharides linked by O-glycosidic bonds

Question 6

What is lactose synthase?

Answer 6

Heterodimer compromising the α-lactalbumin and β4galactosyltransferase -1

Question 7

What is the function of prolactin?

Answer 7

Stimulates the expression of α-lactalbumin in the lactating mammary gland

Question 8

What is α-lactalbumin?

Answer 8

The enzyme that produces the breast milk

Question 9

What is the reversible equation between glucose, galactose and lactose?

Answer 9

Lactose and water —-(lactase)—-> Galactose + Glucose

Question 10

Where is lactase located?

Answer 10

The brush border (microvilli) of the small intestine

Question 11

What is lactase and what is its function?

Answer 11

β-D-galactosidase that catalyses the breakdown of lactose to galactose and glucose

Question 12

What other deficiencies affect the carbohydrate absorption?

Answer 12

Surcease, isomaltase and trehalase deficiencies

Question 13

What is lactase deficiency?

Answer 13

The failure to express the enzyme (lactase) that hydrolyses lactose into galactose and glucose in the small intestine

Question 14

What are some symptoms that occur as milk is ingested for people with IEM??

Answer 14

Stools have a low pH
Stools contain glucose produced by bacteria action on undigested lactose

Question 15

What happens to lactose in lactase-deficient individuals?

Answer 15

Gut bacteria ferment lactose to lactic acid, methane, and acetate

Question 16

What does bacterial fermentation cause?

Answer 16

Abdominal cramps, bloating and nausea

Question 17

What is lactose malabsorption?

Answer 17

Failure to digest or absorb lactose in the small intestine

Question 18

Why does the lactase enzyme decrease in numbers after weaning?

Answer 18

The quantity of lactose taken in is less, if any dairy products are consumed the enzyme cannot break it down so gut bacteria have to do so.

Question 19

What are symptoms of lactose intolerance?

Answer 19

Flatulence
Abdominal discomfort
Bloating
Diarrhea

Question 20

What are the common symptoms of galactosemia?

Answer 20

Failure to thrive
Predisposition to sometimes life-threatening infections
Jaundice
Liver failure

Question 21

What causes jaundice in galactosemia?

Answer 21

The liver is unable to break down bilirubin

Question 22

How does galactose enter the liver?

Answer 22

Freely from the blood to the hepatocytes

Question 23

Where is galactose metabolised?

Answer 23

In the liver

Question 24

Explain the pathway galactose into glucose.

Answer 24

Enters liver through GLUT 2
GALK transforms galactose into galactose-1-phosphate
Galactose-1-phosphate turns into glucose-1-phosphate through GALT
PGM1 converts glucose-1-phosphate into glucose-6-phosphate
Glycolysis

Question 25

Why are cells not equipped or adapted to utilise galactose for metabolism?

Answer 25

Most galactose is removed and metabolised through the liver, excreted through urine

Question 26

How does galactose become galactose-1-phosphate?

Answer 26

Through galactokinase (phosphorylation, so ATP is used up)

Question 27

What is the role of galactose in the body?

Answer 27

Required for glycosylation of glycoproteins and glycolipids in non-liver tissues - Enhances immune system

Question 28

What is the role of galactose in the respiratory system?

Answer 28

Salfated galactose residues

Question 29

What does galactose in the respiratory system prevent?

Answer 29

Pneumonia, Influenza

Question 30

What is the role of galactose in metabolism?

Answer 30

Biosynthesis of many complex carbohydrates

Question 31

What are the complex carbohydrates that galactose biosynthesises?

Answer 31

Glycoproteins, glycolipids

Question 32

What is the role of galactose in the gastrointestinal system?

Answer 32

To maintain bacteria flora

Question 33

Why is the conversion of galactose into glucose thermodynamically not a favorable reaction?

Answer 33

it uses too much ATP (3 molecules)

Question 34

What is the galactose pathway in the liver?

Answer 34

Lactose to Galactose + Glucose (lactase) Galactose to Galactose-1-phosphate + UDP glucose (Galactokinase) Galactose-1-phosphate to Glucose-1-phosphate + UDP galactose (Galactose-1-phosphate uridyl transferase) UDP galactose and UDP glucose are reversible with each other (UDP Galactose-4-epimerase GALE)

Question 35

Why does UDP galactose change to UDP glucose?

Answer 35

UDP galactose is toxic in high quantities so it transforms into UDP glucose which is useful

Question 36

What is classic galactosemia caused by?

Answer 36

A mutation in the galactose-1-phosphate transferase (GALT)

Question 37

What is type II galactosemia caused by?

Answer 37

A mutation in the galactokinase (GALK)

Question 38

What is type III galactosemia caused by?

Answer 38

A mutation in UDP - GAlactose-4-epimerase (GALE)

Question 39

What happens if GALT is not working properly?

Answer 39

Galactose is not converted into glucose so there is a build-up of galactose

Question 40

What is galactose also converted into?

Answer 40

Galactitol and galactonate

Question 41

Which enzyme converts galactose into galactilol?

Answer 41

Aldose reductase

Question 42

Which disease occurs when galactose is converted to excessive galactitol?

Answer 42

Cataracts

Question 43

What is the diagnostic test for PKU?

Answer 43

FeCl3 which detects phenylalanine in urine

Question 44

What happens if phenylalanine is present in the urine?

Answer 44

FeCl3 changes colour to green, blue or black from orange/yellow

Question 45

What enzyme converts phenylalanine into tyrosine?

Answer 45

PAH

Question 46

Where does PAH-mediated hydroxylation occur?

Answer 46

Liver and renal tubules of kidney

Question 47

What is BH4?

Answer 47

A cofactor required for PAH activity

Question 48

What is DHPR? What is its function?

Answer 48

Cofactor required for the hydroxylation of Phenylalanine, Tyrosine, and Tryptophan. Catalyses age recycling of tetrahydrobiopterin

Question 49

What is PAH-mediated hydroxylation the rate-limiting step of?

Answer 49

Intermediary metabolism of L-Phe

Question 50

What is PKU?

Answer 50

PAH deficiency, autosomal recessive. Defects in the production of BH4 which may result in hyperphenylalanine

Question 51

What are the symptoms of PKU?

Answer 51

Increased phenylalanine Increased phenyl-ketones Increased phenylamine Deficiency of tyrosine Fair skin, blue eyes, light blonde hair Mousy or musty door of urine

Question 52

What is the function of phenylalanine?

Answer 52

It is involved in the body's production of melanin, decreased production of phenylalanine so decreased melanin

Question 53

What happens if PKU goes untreated?

Answer 53

Microcephaly Eczematous skin rash Mousy or musty odor in urine Severe mental retardation

Question 54

Why can PKU cause sever mental retardation?

Answer 54

Greatly increased concentration of phenylalanine impairs brain development and function

Question 55

What is the metabolic catabolism of phenylalanine?

Answer 55

Phenylalanine to Tyrosine (Phenylalanine hydroxylate) Tyrosine to p-OH-phenylpyruvate (tyrosine aminotransferase) p-OH-phenylpyruvate to homogenistic acid (4-OH-phenylpyruvate deoxygenase) Homogenistic acid to maleylacetoacetate (homogenistic acid oxidase) Maleylacetoacetate to Fumarylacetoacetate (maleylacetoacetate isomerase) Fumarylacetoacetate to Fumarate + Acetoacetate (fumarylacetoacetate hydrolase)

Question 56

In the phenylalanine metabolic cycle what causes PKU?

Answer 56

Inability to transform phenylalanine to tyrosine

Question 57

In the phenylalanine metabolic cycle what causes Alkaptonuria?

Answer 57

Inability to convert homogenistic acid to maleylacetoacetate

Question 58

What causes alkaptonuria?

Answer 58

Deficiency of the enzyme homogenistic deoxygenate

Question 59

What are the signs of alkaptonuria?

Answer 59

Homogenistic acid and alkapton in urine Blue-black pigmentation in connective tissues Arthritis Urine turns dark with standing or alkalisation

Question 60

What happens in β-oxidation?

Answer 60

Carbon number is reduced by two each time

Question 61

Where does β-oxidation take place?

Answer 61

Mitochondrial matrix

Question 62

What are the carbon units lost during β-oxidation become?

Answer 62

CO2 in the muscle or generate ketone bodies in the liver

Question 63

What are the symptoms of fatty acid oxidation diseases?

Answer 63

Asymptomatic Hypoglycaemia Lethargy Coma Sudden death

Question 64

What causes hypoglycemia in patients with fatty acid oxidation diseases?

Answer 64

There is reduced levels of hepatic glucose, that is why β-oxidation needs to happen.

Question 65

What might cause sudden death in patients with fatty acid oxidation disorders?

Answer 65

Prolonged fasting, acute illness