Amino Acid Diseases

Question 1

What amino acids can be used for the degradation pathways to generate energy?

What does it produce?

What tissues use this pathway?

Answer 1

Valine, isoleucine, and leucine

Produces NADH and FADH2

Muscle and gut (fasting state) use this pathway

Question 2

What amino acid is used in the TCA cycle pathway?

What tissues use this pathway?

Answer 2

Glutamine, lots of glutamine in circulation

Gut, immune cells, and kidney

Question 3

Where are ketone bodies made? How do they provide energy?

Answer 3

They are generated in the liver, providing energy through the TCA cycle

Question 4

Where are glucogenic amino acids made? How do they provide energy?

Answer 4

Glucose is generated from the liver from glucogenic AAs, they are then transported to other tissues and provide energy through the TCA cycle and glycolysis

Question 5

What are the conditionally essential AAs

Answer 5

Sulfur of Cys comes from Met (essential)

Tyr is produced from Phe

Arg is essential for children but NOT adults

Question 6

Pyridoxal-phosphate (B6) action

Answer 6

Transamination and deamination

Question 7

Tetrahydrofolate action

Answer 7

Metabolism of serine, glycine, methionine, and histidine

Question 8

Cobalamins (B12) action

Answer 8

Methionine metabolism

Question 9

Tetrahydrobiopterin action

Answer 9

Hydroxylation of phenylalanine, tyrosine, and tryptophan

Question 10

Thiamine-pyrophosphate (B1) and lipoate action

Answer 10

Oxidative decarboxilation of branched-chain amino acids

Question 11

Aspariginase drug action

Answer 11

Antileukemic drug. Asparagine is required for the growth of fast dividing leukemic cells

Question 12

What happens in glycine encephalopathy?

Answer 12

Deficiency of glycine cleavage enzyme. Elevated glycine in blood and cerebrospinal fluid, intellectual disability, developmental delay

Question 13

What happens in Primary hyperoxaluria type I?

Answer 13

Ca-OAA kidney stones

Question 14

Deficiency in cystathionine synthase, accumulation of homocysteine occurs in urine. Methionine and its metabolites are elevated in the blood. Mental retardation, osteoporosis, MI, and a characteristic discoloration of the lens occur

Answer 14

Homocystinuria

Question 15

Accumulation of cystathione and its metabolites is due to a deficiency in cystathionase. NO SYMPTOMS

Answer 15

Cystathioninuria

Question 16

Deficiency in cystathionine synthase, accumulation of homocysteine occurs in urine. Methionine and its metabolites are elevated in the blood. Mental retardation, osteoporosis, MI, and a characteristic discoloration of the lens occur

Answer 16

Homocystinuria

Question 17

Accumulation of cystathionine and its metabolites is due to a deficiency in cystathionase. NO SYMPTOMS

Answer 17

Cystathioninuria

Question 18

What are the treatments for homocystinuria

Answer 18

Dietary restriction of Met, and supplementation of Cys. Vitamin B6 (PLP) supplementation (if responsive), B12 and folic acid supplementation (if responsive), betaine supplementation (methylation of homocysteine)

Question 19

Due to a deficiency in fumaryl-acetoacetate hydrolase. Accumulation of fumarylacetoacetate and its metabolites, particularly succinyl acetone, in the urine. Characteristic cabbage-like odor occurs

Answer 19

Tyrosinemia type I

Question 20

Due to tyrosine deficiency, white skin, white hair, pink eyes
Eyes and skin sensitive to sunlight, nystagmus, far or near-sightedness

Answer 20

Oculocutaneous albinism type I

Question 21

Disease of the tyrosine degradation pathway, due to homogentisic acid oxidase deficiency. Homogentisic acid accumulates in urine, tissues, and cartilage, which causes crippling arthritis Urine darkens at the surface due to the oxidation of homogentisic acid. It turns black after two hours

Bluish-black eye pigmintation in the sclera of the eye (usually the first sign) and in the cartilage of the ear. Dense, black pigment deposited on the intervertebral disks of the vertebrae

Answer 21

Alkaptonuria

Question 22

Action of Nitisinone drug

Answer 22

Along with controlled dietary intake of Tyr and Phe, it blocks the formation of homogentisate

Question 23

Toxic levels of fumarylacetoacetate in hepatocytes. Leads to hepatic failure, jaundice, cirrhosis, hepatocarcinoma, and failure to thrive. Associated with very high alpha-fetoprotein levels

Answer 23

Tyrosinemia type I

Question 24

High levels of succinylacetone in blood and urine. Kidney failure, high excretion of phosphate in urine, leading to rickets (low bone density)

Answer 24

Tyrosinemia Type I

Question 25

Elevated urine δ-aminolevulinic acid levels (inhibition of heme synthesis). Neurological crises similar to acute intermittent porphyria (change in mental status, abdominal pain, and respiratory failure)

Answer 25

Tyrosinemia Type I

Question 26

Due to phenylalanine hydroxylase deficiency. Mutations in the enzyme and insufficient tetrahydrobiopterin leads to this disease. Treatment includes phe-restrited, Tyr supplemented diet, avoid aspartame, artificial sweetener. Neonatal screening is mandatory

Symptoms include elevated phenylalanine, phenylpyruvate, phenyllactate, and phenylacetate in blood and urine (musty odor of urine). Neurological problems (mental retardation, seizures, tremors, and microcephaly) due to reduced production of catecholamines. Hypopigmentation (light skin, hair, blue eyes), due to reduced melatonin production

Answer 26

Phenylketonuria (PKU)

Question 27

This is necessary for the hydroxylation of Phe (Tyr production), tyrosine (first step of catecholamine synthesis), and Trp (first step of serotonin and melatonin synthesis). Its deficiency causes more severe PKU than mutations in Phe hydroxylase, treatment is supplementation/Kuvan

Answer 27

Tetrahydrobiopterin (BH4)

Question 28

Due to a deficiency in methylmalonyl CoA mutase. Elevated levels of methylmalonyl acid occurs in the blood. Metabollic (methylmalonic) acidosis and developmental problems occur

Answer 28

Methylmalonyl CoA mutase deficiency

Question 29

Due to the deficiency in propionyl CoA carboxylase. Elevated levels of 3-OH propionic acid. Metabolic acidosis and developmental problems

Answer 29

Propionyl-CoA carboxylase deficiency

Question 30

Valine cannot be turned into isobutyryl CoA because a-keto acid dehydrogenase is blocked, Ile cannot be turned into 2-methylbutyryl CoA, and Leucine cannot be turned into Leucine

Symptoms include elevated branched-chain AA (BCAAs), especially leucine in blood). Elevated brached-chain ketoacids (BCKAs) in blood and especially in urine. Maple syrup odor of urine (by 5-7 days after birth) and earwax. Encephalopathy (lethargy, poor feeding, apnea, opisthotonus, coma)

Answer 30

Maple Syrup Urine Disease (MSUD)

Question 31

Management for what disease is BCAA restricted high calorie diet. Usually BCAA-free formulas are supplemented with limited amounts of valine and isoleucine. Leucine is always the most restricted. ALL BCAAs are essential AAs?

Answer 31

Maple Syrup Urine Disease (MSUD)

Question 32

When glutamine is transported to neurons, what is it converted to?

Answer 32

Glutamate and GABA (major NTs)

Question 33

Lack of tryptophan and niacin (vitamin B3) in diet. Characterized by the 4Ds — dermatitis, diarrhea, dementia, and if untreated, death

Answer 33

Pellagra