L.5 AA Metabolism Diseases and Coenzymes

Question 1

Histidinemia

Answer 1

-Histininase deficiency
-Histidine metabolism
-Elevated histidine
in blood/urine, very benign

Question 2

Albinism

Answer 2

• Tyrosinase deficiency
• Tyrosine metabolism
• No melanin production, so are albino

Question 3

Alkaptonuria

Answer 3

• Homogentistic oxidase deficiency
• Tyrosine metabolism
• Homogentisic acid accumulation in urine/tissues (causes oxidation)
• Causes crippling arthritis

Question 4

Tyrosinemia Type I

Answer 4

• Fumaryl-Acetoacetate Hydrolase deficiency
• Tyrosine metabolism
• Accumulation of Fumarylacetoacetate/succinyl acetone in urine (cabbage like odor)
• Accumulation is toxic, causes liver/kidney failure
• Tx: Dietary restriction of phenylalanine/tyrosine, drug blocks production of Fumarylacetoacetate/succinyl acetone

Question 5

Phenylketonuria

Answer 5

-Phenylalanine Hydroxylase deficiency (or BH4) deficiency
Phenylalanine/tyrosine metabolism
-Elevated phenylalanine phenylpyruvate/phenyllactate/phenylacetate in blood/urine (musty odor)
-Neurological problems (reduced production of catecholamines/high levels of phenylalanine prevent other AA entry to brain)
-Hypopigmentation from reduced melanin production (from lack of tyrosine)
Tx: Restrict phenylalanine, avoid aspartame (contains phenylalanine, supplement tyrosine

Question 6

Tetrahydrobiopterin (BH4) Deficiency

Answer 6

-More severe form of PKU
-Affects more than phenylalanine metabolism
-BH4 needed for hydroxylation of: Phenylalanine (tyrosine production), Tyrosine (catecholamine synthesis), Tryptophan (serotonin/melatonin synthesis)
-Elevated phenylalanine phenylpyruvate/phenyllactate/phenylacetate in blood/urine (musty odor)
-Neurological problems
-Hypopigmentation
Tx: provide synthesized BH4

Question 7

Methylmalonic Acidemia

Answer 7

• Methylmalonyl CoA Mutase deficiency/Vit B12 deficiency
• Valine/isoleucine/threonine/methionine metabolism
• Elevated levels of methylmalonyl acid in blood
• Causes metabolic acidosis/developmental problems
• Leads to secondary hyperammonemia bc accumulated metabolites inhibit activation of urea cycle via N-Acetylglutamate

Question 8

Propionic Acidemia

Answer 8

• Propionyl CoA Carboxylase deficiency, biotin deficiency
• Valine/isoleucine/threonine/methionine metabolism
• Elevated 3-OH propionic acid
• Metabolic acidosis/developmental problems
• Leads to secondary hyperammonemia bc accumulated metabolites inhibit activation of urea cycle via N-Acetylglutamate

Question 9

Homocystinuria

Answer 9

-Cystathionine Synthase deficiency/B6
-Methionine Metabolism
-High homocysteine in urine, high methionine and its metabolites in blood
-High homocysteine also from low BH4/B12
-Mental, retardation, osteoporosis, MI risk, lens dislocation
-Causes cysteine to become essential AA
Tx: restrict methionine, supplement cysteine

Question 10

Cystathionuria

Answer 10

• Cystathionase deficiency/B6
• Methionine metabolism
• Accumulation of cystathionine
• No clinical symptom

Question 11

Megaloblastic Anemia

Answer 11

-Folic Acid deficiency
-Folic acid makes Tetrahydrofolate (THF) -> THF makes:Purines,
Thymidine monophosphate (TMP), necessary for DNA synthesis, Methionine
-Histidine/glycine/serine metabolism
-Very Large RBCs (precursors grow, but can’t divide due to not enough TMP for DNA synthesis)

Question 12

Maple Syrup Urine Disease

Answer 12

-Branched Chain a-Keto Acid Dehydrogenase deficiency
-Leucine/valine/isoleucine metabolism
-Accumulation of BCAAs in blood and their keto acids in blood/urine, (maple syrup urine)
-Neurological problems due to BCAAs and their keto acids = inefficient NT synthesis
Tx: BCAA restriction (not entirely limited bc are essential AAs)

Question 13

Pellagra

Answer 13

• Tryptophan/B3 deficiency
• Tryptophan makes Serotonin/Melatonin and NAD/NADP
• Tryptophan metabolism
• Dermatitis, Diarrhea, Dementia, Death

Question 14

B6/Pyridoxal-Phosphate

Answer 14

• Transamination and Deamination
• Methionine metabolism
• Cystathionine B-Synthase
• Cystathionase

Question 15

Folic Acid/Tetrahydrofolate/THF

Answer 15

• One carbon transfer reactions
• Serine, Glycine, Methionine, Histidine metabolism
• Serine -> Glycine
• Methionine Synthase
• Purine and TMP synthesis

Question 16

B12/Cobalmins

Answer 16

• Methionine metabolism
• Methylmalonyl CoA Mutase
• Methionine Synthase

Question 17

Tetrahydrobiopterin/BH4

Answer 17

• Hydroxylation of phenylalanine, tyrosine, tryptophan
• Phenylalanine -> Tyrosine
• Tyrosine -> Catecholamines (dopamine, norepinephrine, epinephrine)
• Tryptophan -> Seratonin/Melatonin

Question 18

Thiamine-Pyrophosphate/B1

Answer 18

• Oxidative Decarboxylation
• Oxidative Decarboxylationof BCAAs
• Pyruvate Dehydrogenase
• a-Ketoglutarate Dehydrogenase
• Glyceraldehyde-3-Phosphate Dehydrogenase

Question 19

Biotin

Answer 19

• Carboxylation

- Propionyl CoA Carboxylase

Question 20

NAD and NADP/Niacin/B3

Answer 20

• Oxioreductases
• Pyruvate Dehydrogenase
• a-Ketoglutarate Dehydrogenase

Question 21

Lipoate/Lipoic Acid

Answer 21

• Pyruvate Dehydrogenase
• a-Ketoglutarate Dehydrogenase
• Glyceraldehyde-3-Phosphate Dehydrogenase

Question 22

FMN and FAD/B2/Riboflavin

Answer 22

-Oxioreductases

Question 23

Panthotenic Acid/ Coenzyme A

Answer 23

-Many reactions in FA, carbohydrate and AA metabolism

Question 24

Vitamin K

Answer 24

-Y-carboxylation of Glutamate

Question 25

Gluconeogenic Nonessential AAs

Answer 25

Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine

Question 26

Glucogenic and Ketogenic Nonessential AAs

Answer 26

Tyrosine

Question 27

Glucogenic Essential AAs

Answer 27

Histidine, Methionine, Valine

Question 28

Glucogenic and Ketogenic Essential AAs

Answer 28

Threonine, Isoleucine, Phenylalanine, Tryptophan

Question 29

Ketogenic Essential AAs

Answer 29

Leucine, Lysine

Question 30

Conditionally Essential AAs

Answer 30

Cysteine (Sulfur from Methionine) Tyrosine (from phenylalanine) Arginine (children)