Disorders of Amino Acid Metabolism

Question 1

Dzs of AA transport affect both

Answer 1

Intestinal and renal epithelial transport

Question 2

Hartnup dz

Answer 2

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

Question 3

Cystinnuria

Answer 3

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

Question 4

Hartnup defect

Answer 4

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

Question 5

Hartnup clinical finding, diagnosis, and therapy

Answer 5

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

Question 6

Trp deficiency of hartnup leads to

Answer 6

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

Question 7

Indicanuria mechanism

Answer 7

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

Question 8

Cystinuria

Answer 8

Forms cystine stones

Most common AA metabolic dz

Question 9

Cystine characteristics

Answer 9

Product of 2 cysteines

Not soluble and forms crystal at high concentrations

Question 10

People with cystinuria lack

Answer 10

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

Question 11

Cystinuria subunits

Answer 11

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

Question 12

Tx of cystinuria

Answer 12

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

Question 13

PKU presentation, clincal findings, defect, and genetics

Answer 13

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

Question 14

Classical PKU

Answer 14

Mutation in phenylalanine hydroxylase

Question 15

Rarer form of PKU

Answer 15

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

Question 16

Dihydropterin reductase rxn

Answer 16

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

Question 17

Phenylpyruvic acid effect

Answer 17

Hurts brain development

Question 18

Why do PKU patients have lighter skin

Answer 18

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

Question 19

How is PKU assayed?

Answer 19

Mass spec to look for Phe levels in blood

Question 20

PKU tx

Answer 20

Reduce Phe in diet…avoid aspartame

Question 21

Trysinemia types 1 and 2

Answer 21

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

Question 22

Tyrosinemia type 1 defect and clinical findings

Answer 22

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)

Question 23

Tyr type 1 other names

Answer 23

Hepato-renal tyrosinemia
Tyrosinosis
Hereditary infantile tyrosinemia

Question 24

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

Answer 24

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

Question 25

Tyr type 1 tx

Answer 25

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

Question 26

Tyr type 2 defect, findings, diagnosis, therapy

Answer 26

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

Question 27

MSUD symptoms and infant signs

Answer 27

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

Question 28

What AA increased in MSUD

Answer 28

Valine, Ile, and Leu (branched chain AAs)

Question 29

Enzyme defect of MSUD

Answer 29

Branched chain ketoacid dehydrogenase…4 different subunits

Question 30

People with MSUD have defective

Answer 30

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

Question 31

MSUD tx

Answer 31

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

Question 32

Homocystinuria/Beta-synthase deficiency mutation

Answer 32

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

Question 33

Beta-synthase def mech

Answer 33

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

Question 34

Normal cysteine synthesis

Answer 34

Comes from methionine and utilizes crystathionine beta-synthase

Question 35

Homocystinuria symptoms

Answer 35

Lens dislocation 
Osteoporosis
Vascular events 
Death 
Mental retardation

Question 36

Homocystinuria tx

Answer 36

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