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1.5 Amino Acidopathies (PKU, MSUD, Alkaptonuria, histidinemia)

Terms in this set (11)

Amino acidopathies


inborn = congenital
Human diseases that affect the metabolism of the amino acids catabolism.

In inborn:
defective enzymes of aa may cause the accumulation of :
- aa derivatives or
-intermediates
to the point that they may become toxic.

can lead to (rare):
-mental retardation
- abnormalities

Tx:
-appropriate nutritional support
- careful monitoring
Phenylketonuria (PKU)
Defect:
Phe Hydroxylase

Phenylalanine (Phe)


normal Phe Hydroxylase (PheH): makes

DoPA -->to Melanin


[Phe ---(PheH)> tyrosine
(using NADPH, and O2)
(release H2O, NADP+)
Tyrosine ---(Tyr.H) --> 3,4,Dihydroxy-Phe --->->->
Melanin]

a dark brown to black pigment occurring in the hair, skin, and iris of the eye in people and animals. It is responsible for tanning of skin exposed to sunlight.
Pathway see page. 2

PKU:
inherited defect in the gene that codes for phenylalanine hydroxylase.


without Phe Hydroxylase:
(Phe can't convert to tyr.)

producing:
PhenylAcetate
Phenyl-Lactate

(if Phe hydroxyls present these 2 are low)
PKU Sx


no melanin:
pigmentation deficiency:
fair hair, light skin, blue eyes


neurochemical causes is unknown:
perhaps lacking dopamine:

3,4-dihydroxy-Phenylalanine = Dopa.
- Mental retardation
- failure to walk or talk
- seizures
- hyperactivity
- tremor
- microcephaly
- no growth

Ranging:
gross dev. disabilities to
no major Sx.

neurological Sx = not completely known.
PKU Dx & detection


detect: blood Phe level.

Most states requires
testing PKU of all newborn.
at birth, PKU = normal of Phe in blood (<2mg/dL).

after weeks, Phe increases
(12-15 mg/dL) ==> elevates Phe.Pyruvate (in urine).
PKU Tx


Goal: Provide enough Phe to enable basic function to cont. but no excess.
excess can be fatal.
Blood Phe kept ~ 10mg/dL by feeding synthetic aa which is low in Phe,

supplement with low Phe in food.
Maple Syrup Urine Disease
[inherited]
(MSUD)


Branched Chain Amino Acids
- Valine
- leucine
-Isoleucine

step 1: aminotransferase
step 2: BCAA Decarboxylase is defective
Defective:
BCAA Decarboxylase.

BCAA & their corresponding α-keto acid

all end up in urine.

smell of maple syrup.
clinical

MSUD

Sx:
- vomiting
- lethargy
- Severe brain damage

infants:
few survived beyond 1 year.
MSUD has a high mortality rate.


Tx:

reduce BCAA
(egg white has BCAA)

and their corresponding
α-keto acid,

reduce only to certain extend to prevent a deficiency of BCAA.
Alkapton-uria
(AKU)
benign disease

Defective:
Homogentisate Oxidase
(HGO)

without HGO,
(start product)
tyr can't
make
(end products)
fumarate and acetoacetate



once Homogentisic acid expose to air, air oxidizes it, and it turns black (urine black).
Cause & Clinical:

without
Homogenitase oxidase

intermediate product:
homogenitasic acid
will increase URINE.


later, black pigment in cartilage and other connective tissues causing
arthritis.

discoloration:
- skin
- ears
- sclera
- sweat
AKU
Tx:
treat Sx if needed.
no major treatment

it's benign.
Histidinemia

defective:
Histidase

(FIRST enzyme in the catabolism of histidine.)


more histidine in urine
clinical:

mental retardation (common)
- difficult with speech & language skills

Sx: none

Tx:
restrict histidine intake
(lower in blood)
- this may impair growth & development
Overall
these diseases varies from population to population

e.g. hetero mix-culture of NY. exhibits 1 in 180,000 case of histidnemia.
while homogenous of Japan, only 1 in 9600 cases
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