Amino Acid Diseases Flashcards
What amino acids can be used for the degradation pathways to generate energy?
What does it produce?
What tissues use this pathway?
Valine, isoleucine, and leucine
Produces NADH and FADH2
Muscle and gut (fasting state) use this pathway
What amino acid is used in the TCA cycle pathway?
What tissues use this pathway?
Glutamine, lots of glutamine in circulation
Gut, immune cells, and kidney
Where are ketone bodies made? How do they provide energy?
They are generated in the liver, providing energy through the TCA cycle
Where are glucogenic amino acids made? How do they provide energy?
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
What are the conditionally essential AAs
Sulfur of Cys comes from Met (essential)
Tyr is produced from Phe
Arg is essential for children but NOT adults
Pyridoxal-phosphate (B6) action
Transamination and deamination
Tetrahydrofolate action
Metabolism of serine, glycine, methionine, and histidine
Cobalamins (B12) action
Methionine metabolism
Tetrahydrobiopterin action
Hydroxylation of phenylalanine, tyrosine, and tryptophan
Thiamine-pyrophosphate (B1) and lipoate action
Oxidative decarboxilation of branched-chain amino acids
Aspariginase drug action
Antileukemic drug. Asparagine is required for the growth of fast dividing leukemic cells
What happens in glycine encephalopathy?
Deficiency of glycine cleavage enzyme. Elevated glycine in blood and cerebrospinal fluid, intellectual disability, developmental delay
What happens in Primary hyperoxaluria type I?
Ca-OAA kidney stones
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
Homocystinuria
Accumulation of cystathione and its metabolites is due to a deficiency in cystathionase. NO SYMPTOMS
Cystathioninuria
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
Homocystinuria
Accumulation of cystathionine and its metabolites is due to a deficiency in cystathionase. NO SYMPTOMS
Cystathioninuria
What are the treatments for homocystinuria
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)
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
Tyrosinemia type I
Due to tyrosine deficiency, white skin, white hair, pink eyes
Eyes and skin sensitive to sunlight, nystagmus, far or near-sightedness
Oculocutaneous albinism type I
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
Alkaptonuria
Action of Nitisinone drug
Along with controlled dietary intake of Tyr and Phe, it blocks the formation of homogentisate
Toxic levels of fumarylacetoacetate in hepatocytes. Leads to hepatic failure, jaundice, cirrhosis, hepatocarcinoma, and failure to thrive. Associated with very high alpha-fetoprotein levels
Tyrosinemia type I
High levels of succinylacetone in blood and urine. Kidney failure, high excretion of phosphate in urine, leading to rickets (low bone density)
Tyrosinemia Type I
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)
Tyrosinemia Type I
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
Phenylketonuria (PKU)
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
Tetrahydrobiopterin (BH4)
Due to a deficiency in methylmalonyl CoA mutase. Elevated levels of methylmalonyl acid occurs in the blood. Metabollic (methylmalonic) acidosis and developmental problems occur
Methylmalonyl CoA mutase deficiency
Due to the deficiency in propionyl CoA carboxylase. Elevated levels of 3-OH propionic acid. Metabolic acidosis and developmental problems
Propionyl-CoA carboxylase deficiency
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)
Maple Syrup Urine Disease (MSUD)
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?
Maple Syrup Urine Disease (MSUD)
When glutamine is transported to neurons, what is it converted to?
Glutamate and GABA (major NTs)
Lack of tryptophan and niacin (vitamin B3) in diet. Characterized by the 4Ds — dermatitis, diarrhea, dementia, and if untreated, death
Pellagra
