Fate of Carbon Skeleton in Amino Acid pt.2 Flashcards
How is phenylalanine catabolised?
It is hydroxylated to tyrosine by the enzyme phenylalanine hydroxylase
What is the co-factor for phenylalanine hydroxylase?
tetrahydrobiopterin
What 3 situations may lead to Phenylketonuria?
deficiency of phenylalanine hydroxylase
deficiency of tetrahydrobiopterin
deficiency in the reductase that regenerates the co-factor (dihydropteridine reductase)
What characterizes phenylketonuria?
it is characterized by the accumulation of phenyl ketones in the blood and their excretion in the urine
How are the compound derivatives of phenylalanine formed and what are they?
by transamination
they are phenylpyruvic acid, phenylacetate and phenyllactate (reduced forms of former)
What imparts the mousy odor of urine in phenylketonuriacs?
phenylacetate
When does the musty odor of urine occur in phenylketonuriacs?
2-6 weeks after elevated blood phenylalanine
Apart from musty odor of breath or urine, what other symptoms do phenylketonuriacs present with?
severe mental retardation
low IQ
dilution of hair and skin pigmentation
In terms of genetics, what type of disease is PKU?
autosomal recessive disease
How can PKU be managed?
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
If the symptoms of PKU are caused by excess Phe and its metabolites and since Phe is essential, what can be done?
treatment will involve careful monitoring of Phe intake just enough for protein synthesis without accumulating Phe
Phenylketonuriacs should avoid processed food and beverages containing a food additive ……………
aspartame
The 4 metabolic fates of tyrosine
- catabolism to acetoacetyl CoA
- synthesis of catecholamines
- synthesis of melanin
- synthesis of thyroid hormones
How is tyrosine converted to dihydroxyphenylalanine (L-DOPA)?
it is oxidized by tyrosine hydroxylase with enzyme co-factor tetrahydrobiopterin
Dihydroxyphenylalanine(L-DOPA) is a metabolic precursor to ………
dopamine
Tyrosine is a precursor to pigment molecules called ………. that are produced from ………….
melanin
dopaquinone
The 2 primary melanins and their colours?
eumelanin - black
pheomelanin - yellow/red
What makes pheomelanin have its colour?
the sulfur in the cysteine that is combined with dopaquinone
3 main rxns in tyrosine catabolism
transamination
dioxygenation
isomerization rxns
What is Tyrosinemia?
a condition characterized by the accumulation and excretion of tyrosine and its metabolites
What condition my cause temporarily high tyrosine levels in 10% of neonates?
Vitamin C deficiency or immature liver enzymes due to prematurity
The occurrence of tyrosinemia in males and females
happens in males and females equally
What is Type 1 Tyrosinemia characterized by?
deficiency of fumaryl acetoacetase
Type 1 Tyrosinemia is associated with
the accumulation of maleyl acetoacetate and fumaryl acetoacetate
When can the 2 forms of Type 1 Tyrosinemia and when do they manifest?
acute form - a few months after birth
chronic form - around 1 year after birth
Symptoms of the acute Type 1 Tyrosinemia
poor appetite and failure to grow normally
vomiting, diarrhoea and bloody stool
cabbage-like odour, jaundice, hepatitis
irritability and lethargy
Symptoms of chronic Type 1 Tyrosinemia
liver cirrhosis
polyneuropathy and kidney problems
episodes of intense abdominal pains
heart muscle weakness
Chronic Type 1 Tyrosinemia is otherwise referred to as
Hepato-renal Tyrosinemia
What is Type 2 Tyrosinemia characterized by?
deficiency of tyrosine aminotransferase
What is Type 2 Tyrosinemia associated with?
eye and skin lesions
mental retardation
When do symptoms of Type 2 Tyrosinemia start and what are some of them?
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%
Type 2 Tyrosinemia is otherwise called
Oculo-cutaneous Tyrosinemia or Richner-Hanhart Syndrome
Type 3 Tyrosinemia is characterized by
deficiency of 4-hydroxy phenylpyruvate dioxygenase (4HPD)
Type 3 Tyrosinemia is associated with
Intellectual disability
Seizures
Periodic loss of balance or coordination(intermittent attaxia)
What is Homogentisic Aciduria characterized by?
the deficiency of Homogentisate 1,2 dioxygenase
Homogentisic Aciduria is associated with
accumulation and excretion of large amounts of homogentisic acid
What leads to darkening of napkins of individuals with Homogentisic Aciduria?
exposure of homogentisic acid to air polymerizes it to alkapton
Symptoms of Homogentisic Aciduria
Alkapton deposits in bones, connective tissue and other organs leading to ochronosis
Albinism is characterized by
deficiency of tyrosinase
Associations of Albinism
Defective synthesis of melanin in hair, skin and eyes
Extreme sensitivity to light
Poor eyesight
Highly susceptible to sunburn and skin cancer
The genetic association with albinism is
it is an autosomal recessive genetic mutation in the tyrosinase gene
Histidinaemia is characterized by
deficiency in histidine ammonia lyase
Histidinaemia is associated with
high levels of histidine in blood and urine
Symptoms of Histidineamia
speech defects
mental retardation
Deficiency and vitamin B12(folic acid) will result in
excretion of excessive amounts of formiminoglutamate(FIGLU)
How is Hydantoin 5 propionate excreted?
through the urine
Catecholamines are amino derivatives of catechol and they are
DOPA(Dihydroxyphenyl alanine)
dopamine
epinephrine
norepinephrine
4 reactions of that form catecholamines and their enzymes
Tyrosine —-> L-DOPA (tyrosine hydroxylase)
L-DOPA —–> Dopamine + carbon dioxide (aromatic acid decarboxylase)
Dopamine —> Norepinephrine (Dopamine β-hydroxylase)
Norepinephrine —> Epinephrine (requires S-adenosyl methionine)
What are the 2 steps that convert tryptophan to serotonin
Tryptophan —> 5-hydroxytryptophan by trp hydroxylase, requires tetrahydrobiopterin
5-hydroxytryptophan —> serotonin + carbon dioxide by aromatic acid decarboxylase
Parts of the body where serotonin is formed
brain(neurotransmitter; regulation of mood, sleep and attitude)
platelets(platelet aggregation, vasoconstriction)
smooth muscles(contraction)
GIT (enterochromaffin cells; major storage site)
Serotonin will go through 2 steps to form
melatonin
Uses of melatonin
induces skin lightening
supresses ovarian function
possible use in sleep disorders
Which amino acid is the precursor of nicotinic acid
tryptophan
What is the precursor of serine
glucose
What is the precursor of serine
glucose
What amino acid is involved in the production of glycine?
serine
