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Flashcards in Disorders of Amino Acid Metabolism Deck (36)
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1
Q

Dzs of AA transport affect both

A

Intestinal and renal epithelial transport

2
Q

Hartnup dz

A

Impaired transport of neutral AAs and deficiency of some essential AAs (like tryptophan) may occur

3
Q

Cystinnuria

A

Dibasic AAs (cysteine, ornithine, arginine, lysine) are affected but no nutritional deficit despite fact that lysine is essential

4
Q

Hartnup defect

A

Intestinal and renal tubular reabsorption defect of neutral AAs
Tryptophan deficiency leads to nicotinic acid and serotonine deficiency

5
Q

Hartnup clinical finding, diagnosis, and therapy

A

Photodermatitis, cerebellar ataxia…sometimes asymptomatic
High levels of neutral AAs in urine and low levels in plasma
Nicotinamide 40-300 mg/day…sun protection

6
Q

Trp deficiency of hartnup leads to

A

Dementia, dermatitis, and diarrhea
Similar to nicotinic acid def dz and pellegra
Trp is precurosr to nicotinic acid

7
Q

Indicanuria mechanism

A

Converted to indole in gut, reabsorbed into blood, excreted in urine causing bluish urine or blue diaper syndrome
Indole is oxidized to form indigo blue

8
Q

Cystinuria

A

Forms cystine stones

Most common AA metabolic dz

9
Q

Cystine characteristics

A

Product of 2 cysteines

Not soluble and forms crystal at high concentrations

10
Q

People with cystinuria lack

A

Transporter in proximal tubule of kidney that absorbs cystine from urine stream and puts it back in blood…cystine levels are much higher in urine of these people and leads to crystals

11
Q

Cystinuria subunits

A

SLC7A9 and SLC3A1…mutation in either one can lead to cystinuria

12
Q

Tx of cystinuria

A

Water
Penicillamine which reduces cystine to cysteines which are more soluble
Extracorporeal shock wave lithotripsy (basically an X-ray) can be used to break up stones

13
Q

PKU presentation, clincal findings, defect, and genetics

A

Mental retardation and fair skin
Phenylalanine hydroxylase (liver and kidney)
Increased amounts of ketoacids such as phenylpyruvic acid
Auto rec

14
Q

Classical PKU

A

Mutation in phenylalanine hydroxylase

15
Q

Rarer form of PKU

A

Defect in dihydripterin reductase whih makes a cofactor (tetrahydrobiopterin) needed by phenylalanine hydroxylase

16
Q

Dihydropterin reductase rxn

A

Takes dihydropterin to tetrahydrobiopterin so that phenylalanine hydroxylase can convert phenylalanine to tyrosine

17
Q

Phenylpyruvic acid effect

A

Hurts brain development

18
Q

Why do PKU patients have lighter skin

A

Phe never converted to Tyr so decreased melanin, proteins, dopamine

19
Q

How is PKU assayed?

A

Mass spec to look for Phe levels in blood

20
Q

PKU tx

A

Reduce Phe in diet…avoid aspartame

21
Q

Trysinemia types 1 and 2

A

Defects in enzymes that break down tyrosine
2 - tyrosine aminotransferase that converts tyrosine to 4HPP
1 - FAA hydrolase that converts FAA to fumarate and acetoacetate

22
Q

Tyrosinemia type 1 defect and clinical findings

A

Enzyme defect is fumarylacetoacetate hydroxylase
Acute infantile form - severe liver failure, vomiting, bleeds, spesis, hypoglycemia, renal tubulopathy (Fanconi Syndrome)
Chronic form - Hepatomegaly, cirrhosis, grwoth retardation, rickets, hematoma, tubulopathy, neuropathy and ab pain (due to porphyrines)

23
Q

Tyr type 1 other names

A

Hepato-renal tyrosinemia
Tyrosinosis
Hereditary infantile tyrosinemia

24
Q

Tyr type 1 inheritance…metabolic effect…where is enzyme expressed?

A

Auto rec
Buildup of fumaryl acetoacetate and succinyl acetone…decrease in fumarate and acetoacetate
Enzyme expressed more in liver and prox renal tubular epithelial cells

25
Q

Tyr type 1 tx

A

Nitisinone (NTBC) - blocks second step in tyrosine degradation pathway (4-OH phenylpyruvate dioxygenase) and prevents accumulation of FAA and conversion to succinylacetone…prescribe ASAP
Tyrosine and Phe restricted diet
Liver trasnplant

26
Q

Tyr type 2 defect, findings, diagnosis, therapy

A

Cytosolic tyrosine aminotransferase
Painful corneal lesios (lacrimation, photophobia, scars), mild mental retardation
High Tyr and Phe levels
Tyrosine and Phe restricted diet

27
Q

MSUD symptoms and infant signs

A

Poor appetite, irrtability, maple smelling urine, mental retardation, seizures, death if untreated
Lose sucking reflex and become limp with episdoes of rigidity

28
Q

What AA increased in MSUD

A

Valine, Ile, and Leu (branched chain AAs)

29
Q

Enzyme defect of MSUD

A

Branched chain ketoacid dehydrogenase…4 different subunits

30
Q

People with MSUD have defective

A

BCKD protein complex that normally breaks down leucine, valine, Ile

31
Q

MSUD tx

A
Restrict diet (only reduce)
Some can also take thiamine (cofactor of branched chain ketoacid dehydrogenase)
32
Q

Homocystinuria/Beta-synthase deficiency mutation

A

Crystathione beta synthase is defective and cannot take homocysteine to crystathionine
CBS gene

33
Q

Beta-synthase def mech

A

Accumulation of homocysteine which is excreted in urine…can interact with cysteines of proteins…can cause lens dislocation

34
Q

Normal cysteine synthesis

A

Comes from methionine and utilizes crystathionine beta-synthase

35
Q

Homocystinuria symptoms

A
Lens dislocation 
Osteoporosis
Vascular events 
Death 
Mental retardation
36
Q

Homocystinuria tx

A
Try pyridoxine (vitamin B6 cofactor of CBS) in all...increases CBS activity 
Methionine restricted and cysteine supplemented