Fate of Carbon Skeleton in Amino Acid pt.2

Question 1

How is phenylalanine catabolised?

Answer 1

It is hydroxylated to tyrosine by the enzyme phenylalanine hydroxylase

Question 2

What is the co-factor for phenylalanine hydroxylase?

Answer 2

tetrahydrobiopterin

Question 3

What 3 situations may lead to Phenylketonuria?

Answer 3

deficiency of phenylalanine hydroxylase
deficiency of tetrahydrobiopterin
deficiency in the reductase that regenerates the co-factor (dihydropteridine reductase)

Question 4

What characterizes phenylketonuria?

Answer 4

it is characterized by the accumulation of phenyl ketones in the blood and their excretion in the urine

Question 5

How are the compound derivatives of phenylalanine formed and what are they?

Answer 5

by transamination

they are phenylpyruvic acid, phenylacetate and phenyllactate (reduced forms of former)

Question 6

What imparts the mousy odor of urine in phenylketonuriacs?

Answer 6

phenylacetate

Question 7

When does the musty odor of urine occur in phenylketonuriacs?

Answer 7

2-6 weeks after elevated blood phenylalanine

Question 8

Apart from musty odor of breath or urine, what other symptoms do phenylketonuriacs present with?

Answer 8

severe mental retardation
low IQ
dilution of hair and skin pigmentation

Question 9

In terms of genetics, what type of disease is PKU?

Answer 9

autosomal recessive disease

Question 10

How can PKU be managed?

Answer 10

restriction of phenylalanine containing diets
taking diets high in tyrosine for first 4-5 years
protein diet restriction should be enforced for years
diets should contain high levels of tetrahydrobiopterin

Question 11

If the symptoms of PKU are caused by excess Phe and its metabolites and since Phe is essential, what can be done?

Answer 11

treatment will involve careful monitoring of Phe intake just enough for protein synthesis without accumulating Phe

Question 12

Phenylketonuriacs should avoid processed food and beverages containing a food additive ……………

Answer 12

aspartame

Question 13

The 4 metabolic fates of tyrosine

Answer 13

• catabolism to acetoacetyl CoA
• synthesis of catecholamines
• synthesis of melanin
• synthesis of thyroid hormones

Question 14

How is tyrosine converted to dihydroxyphenylalanine (L-DOPA)?

Answer 14

it is oxidized by tyrosine hydroxylase with enzyme co-factor tetrahydrobiopterin

Question 15

Dihydroxyphenylalanine(L-DOPA) is a metabolic precursor to ………

Answer 15

dopamine

Question 16

Tyrosine is a precursor to pigment molecules called ………. that are produced from ………….

Answer 16

melanin

dopaquinone

Question 17

The 2 primary melanins and their colours?

Answer 17

eumelanin - black

pheomelanin - yellow/red

Question 18

What makes pheomelanin have its colour?

Answer 18

the sulfur in the cysteine that is combined with dopaquinone

Question 19

3 main rxns in tyrosine catabolism

Answer 19

transamination
dioxygenation
isomerization rxns

Question 20

What is Tyrosinemia?

Answer 20

a condition characterized by the accumulation and excretion of tyrosine and its metabolites

Question 21

What condition my cause temporarily high tyrosine levels in 10% of neonates?

Answer 21

Vitamin C deficiency or immature liver enzymes due to prematurity

Question 22

The occurrence of tyrosinemia in males and females

Answer 22

happens in males and females equally

Question 23

What is Type 1 Tyrosinemia characterized by?

Answer 23

deficiency of fumaryl acetoacetase

Question 24

Type 1 Tyrosinemia is associated with

Answer 24

the accumulation of maleyl acetoacetate and fumaryl acetoacetate

Question 25

When can the 2 forms of Type 1 Tyrosinemia and when do they manifest?

Answer 25

acute form - a few months after birth | chronic form - around 1 year after birth

Question 26

Symptoms of the acute Type 1 Tyrosinemia

Answer 26

poor appetite and failure to grow normally vomiting, diarrhoea and bloody stool cabbage-like odour, jaundice, hepatitis irritability and lethargy

Question 27

Symptoms of chronic Type 1 Tyrosinemia

Answer 27

liver cirrhosis polyneuropathy and kidney problems episodes of intense abdominal pains heart muscle weakness

Question 28

Chronic Type 1 Tyrosinemia is otherwise referred to as

Answer 28

Hepato-renal Tyrosinemia

Question 29

What is Type 2 Tyrosinemia characterized by?

Answer 29

deficiency of tyrosine aminotransferase

Question 30

What is Type 2 Tyrosinemia associated with?

Answer 30

eye and skin lesions | mental retardation

Question 31

When do symptoms of Type 2 Tyrosinemia start and what are some of them?

Answer 31

``` begin in early childhood excessive tearing abnormal sensitivity to light eye pain and redness painful skin lesions on palm and soles intellectual disability in about 50% ```

Question 32

Type 2 Tyrosinemia is otherwise called

Answer 32

Oculo-cutaneous Tyrosinemia or Richner-Hanhart Syndrome

Question 33

Type 3 Tyrosinemia is characterized by

Answer 33

deficiency of 4-hydroxy phenylpyruvate dioxygenase (4HPD)

Question 34

Type 3 Tyrosinemia is associated with

Answer 34

Intellectual disability Seizures Periodic loss of balance or coordination(intermittent attaxia)

Question 35

What is Homogentisic Aciduria characterized by?

Answer 35

the deficiency of Homogentisate 1,2 dioxygenase

Question 36

Homogentisic Aciduria is associated with

Answer 36

accumulation and excretion of large amounts of homogentisic acid

Question 37

What leads to darkening of napkins of individuals with Homogentisic Aciduria?

Answer 37

exposure of homogentisic acid to air polymerizes it to alkapton

Question 38

Symptoms of Homogentisic Aciduria

Answer 38

Alkapton deposits in bones, connective tissue and other organs leading to ochronosis

Question 39

Albinism is characterized by

Answer 39

deficiency of tyrosinase

Question 40

Associations of Albinism

Answer 40

Defective synthesis of melanin in hair, skin and eyes Extreme sensitivity to light Poor eyesight Highly susceptible to sunburn and skin cancer

Question 41

The genetic association with albinism is

Answer 41

it is an autosomal recessive genetic mutation in the tyrosinase gene

Question 42

Histidinaemia is characterized by

Answer 42

deficiency in histidine ammonia lyase

Question 43

Histidinaemia is associated with

Answer 43

high levels of histidine in blood and urine

Question 44

Symptoms of Histidineamia

Answer 44

speech defects | mental retardation

Question 45

Deficiency and vitamin B12(folic acid) will result in

Answer 45

excretion of excessive amounts of formiminoglutamate(FIGLU)

Question 46

How is Hydantoin 5 propionate excreted?

Answer 46

through the urine

Question 47

Catecholamines are amino derivatives of catechol and they are

Answer 47

DOPA(Dihydroxyphenyl alanine) dopamine epinephrine norepinephrine

Question 48

4 reactions of that form catecholamines and their enzymes

Answer 48

Tyrosine ----> L-DOPA (tyrosine hydroxylase) L-DOPA -----> Dopamine + carbon dioxide (aromatic acid decarboxylase) Dopamine ---> Norepinephrine (Dopamine β-hydroxylase) Norepinephrine ---> Epinephrine (requires S-adenosyl methionine)

Question 49

What are the 2 steps that convert tryptophan to serotonin

Answer 49

Tryptophan ---> 5-hydroxytryptophan by trp hydroxylase, requires tetrahydrobiopterin 5-hydroxytryptophan ---> serotonin + carbon dioxide by aromatic acid decarboxylase

Question 50

Parts of the body where serotonin is formed

Answer 50

brain(neurotransmitter; regulation of mood, sleep and attitude) platelets(platelet aggregation, vasoconstriction) smooth muscles(contraction) GIT (enterochromaffin cells; major storage site)

Question 51

Serotonin will go through 2 steps to form

Answer 51

melatonin

Question 52

Uses of melatonin

Answer 52

induces skin lightening supresses ovarian function possible use in sleep disorders

Question 53

Which amino acid is the precursor of nicotinic acid

Answer 53

tryptophan

Question 54

What is the precursor of serine

Answer 54

glucose

Question 54

What is the precursor of serine

Answer 54

glucose

Question 55

What amino acid is involved in the production of glycine?

Answer 55

serine