Metabolic Disorders: Branched-Chain Amino Acid, Tryptophan, Cystine Disorders Flashcards by Kyra Catedral

Branched-Chain Amino Acid Disorders
• a defect or deficiency of the branched chain ketoacid dehydrogenase complex in which elevated quantities of leucine, isoleucine, valine, and their corresponding oxoacids accumulate in body fluids

MAPLE SYRUP URINE DISEASE (MSUD)

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Branched-Chain Amino Acid Disorders

MAPLE SYRUP URINE DISEASE (MSUD)

• a defect or deficiency of the _______complex in which elevated quantities of (3), and their corresponding oxoacids accumulate in body fluids

branched chain ketoacid dehydrogenase

leucine, isoleucine, valine

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Branched-Chain Amino Acid Disorders

MAPLE SYRUP URINE DISEASE (MSUD)
• An increase in___\ may cause competitive inhibition with other precursors of neurotransmitters causing the neurologic
manifestations

leucine

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MAPLE SYRUP URINE DISEASE (MSUD)

Branched-Chain Amino Acid Disorders

• _______ is the most severe and common form with symptoms of poor suck, lethargy, hypo and hypertonia, opisthotonic posturing, seizures, and coma developing 4-7 days after birth

Classical MSUD

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Branched-Chain Amino Acid Disorders

MSUD

• Odor of maple syrup in urine may be detected as soon as_____
symptoms appear

neurological

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Branched-Chain Amino Acid Disorders

MSUD MANAGEMENT AND TESTING
• Management: dietary restriction of…

branched-chain amino acids

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Branched-Chain Amino Acid Disorders

MSUD MANAGEMENT AND TESTING

• Screening test:

• 2,4-dinitrophenylhydrazine test

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Branched-Chain Amino Acid Disorders

MSUD

• 2,4-dinitrophenylhydrazine test

• 1 mL of urine+ 10 drops of 0.2% 2,4-DNPH in 2N HCI
• Wait 10 minutes
• Observe for______

yellow turbidity or precipitate

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Branched-Chain Amino Acid Disorders

• an important class of inherited metabolic disorders (IMD) arising due to a defect in intermediary metabolic pathways of carbohydrate, amino acids and fatty acid oxidation

• leads to accumulation of organic acids in tissues and their subsequent excretion in urine etion in urine

ORGANIC ACIDEMIAS

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Branched-Chain Amino Acid Disorders

• Common organic acidemias (3)

• Propionic acidemia
• Methylmalonic acidemia
• Isovaleric acidemia

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Branched-Chain Amino Acid Disorders

• Urine smells like “sweaty feet” 👣

• Deficiency of isovaleryl-CoA in leucine metabolism

Isovaleric Acidemia

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Branched-Chain Amino Acid Disorders

Sweaty feet is due to…

due to isovalerylglycine accumulation

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Branched-Chain Amino Acid Disorders

Isovaleric Acidemia

• Deficiency of______ in leucine metabolism

isovaleryl-CoA

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Branched-Chain Amino Acid Disorders

Propionic & Methylmalonic Acidemia
• Caused by errors in converting isoleucine, valine, threonine, & methionine to succinyl-CoA
• ______ is the precursor of methylmalonic acid

Propionic acid

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Tryptophan Disorders

• Presence of intestinal disorders that prevent the metabolism of tryptophan

• Obstruction
• Presence of abnormal bacteria
• Hartnup disease

INDICANURIA

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Tryptophan Disorders

• Excessive amounts of tryptophan is converted to indole and reabsorbed in the circulation
• Indole is converted to indican in the liver and excreted in urine
• Urine is colorless then turns to indigo upon exposure to air

INDICANURIA

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Tryptophan Disorders

INDICANURIA

• Excessive amounts of_____ is converted to_____ and reabsorbed in the circulation
• Indole is converted to____ in the____ and excreted in urine
• Urine is colorless then turns to____ upon____

tryptophan; indole

indican; liver

indigo; exposure to air

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Tryptophan Disorders

• Caused by a mutation on the gene that encodes for the BOAT1 protein

HARTNUP DISEASE

Tryptophan Disorders

• A sodium-dependent co-transport protein for the absorption of neutral amino acids present at the apical surface of the small intestine and renal tubular cells

• excessive excretion of neutral amino acids in urine and feces

B0AT1 protein

Tryptophan Disorders

• Characterized by photosensitive skin rash and neuropsychiatric symptoms

HARTNUP

Tryptophan Disorders

HARTNUP

•_____ deficiency: pellagra-like skin eruptions (tryptophan is precursor for niacin)

Niacin

Tryptophan Disorders

5-HIAA
•_______ is produced from typtophan by argentaffin cells in the intestine

• Only small amounts of its degradation product, 5-hydroxyindoleacetic acid, are released in urine

Serotonin

Tryptophan Disorders

• A carcinoid tumor that produces excess serotonin and results into elevated urinary levels of 5-HIAA

Argentaffinoma

Tryptophan Disorders

5-HIAA TESTS

• Addition of nitrous acid and 1-nitroso-2-naphthol
• Change in urine color to_____

purple to black

5-HIAA Tryptophan Disorders • Dietary restrictions: no intake of food rich in serotonin (examples??) • Drug restrictions: withhold drugs like ***phenothiazines and acetanilids*** for 72 hours prior to testing

bananas, avocados, pineapples, plums, kiwi, eggplant, walnuts, tomatoes

Tryptophan Disorders Indicanuria • Normally,_____ is reabsorbed or excreted as_____ in feces. • In certain conditions, excess indole is converted to____ and excreted in urine. • Indican is colorless but turns____ when oxidized

tryptophan; indole indican blue

Tryptophan Disorders (“Blue Diaper Syndrome” in infants).

INDICANURIA

Tryptophan Disorders 5-Hydroxyindoleacetic Acid (5-HIAA) • Serotonin is derived from____ and is carried by platelets. • Normally, small amounts of____ (serotonin breakdown product) are excreted in urine. • Carcinoid tumors of____ produce excess serotonin, increasing 5-HIAA levels.

tryptophan 5-HIAA argentaffin cells

Tryptophan Disorders INDICAN • Normal excretion:_____ •______ = Carcinoid tumor suspicion

2–8 mg/day > 25 mg/24 hrs

CYSTINE DISORDERS • Inherited disorders •_______: defect in the renal tubular transport of amino acids •_______: inherited defect in the lysosomal membranes that results into cystine accumulation in cells •_______: defect in the metabolism of methionine

Cystinuria Cystinosis Homocystinuria

Cystine Disorders • inheritable, autosomal recessive genetic defect that affects the ***proximal renal tubular reabsorption of cystine*** • also affects ***lysine, ornithine, and arginine,*** but only cystine is clinically significant as it is the only amino acid in this group that will form stones • Cystine crystals appear in urine

CYSTINURIA

Cystine Disorders Cystinuria • Urine odor:

sulfur/rotten egg

Cystine Disorders CYANIDE-NITROPRUSSIDE TEST FOR CYSTINE • 3 mL of urine + 2 mL sodium cyanide • Wait 10 minutes • Add 5 drops of 5% sodium nitroprusside • Observe for______

red-purple color

CYSTINE DISORDERS • a rare autosomal recessive lysosomal storage disorder in which the ***amino acid cystine accumulates in the lysosomes of cells***

CYSTINOSIS

CYSTINE DISORDERS Cystinosis • Most common type:_____ • Defective transport leads to accumulation and crystallization of cystine in the lysosomes. • Affected cells suffer from mitochondrial dysfunction, oxidative stress, and inflammation and, in the end, undergo apoptosis. • Since lysosomes are part of every cell type cystine accumulation occurs throughout the whole body, making cystinosis a systemic disease. • Tx: aminothiol cysteamine, used for over 20 years

infantile nephropathic type

CYSTINE DISORDERS • ***Deficiency of cystationine synthase enzyme*** which is part of methionine metabolism

HOMOCYSTINURIA

CYSTINE DISORDERS HOMOCYSTINURIA • Deficiency of ______enzyme which is part of methionine metabolism

cystationine synthase

CYSTINE DISORDERS • Homocysteine accumulates and dimerizes to form the disulfide homocystine, which is excreted in the urine • ***prone to thrombosis*** and has adverse effects on connective tissue particularly the ***eyes and skeleton;*** adverse ***neurologic effects may be due to thrombosis or a direct effect***

Homocystinuria

CYSTINE DISORDERS Homocystinuria • Detected by ______test followed by______

cyanide-nitroprusside silver nitroprusside test

Marked by elevated cystine levels in urine, but not due to metabolic defects. Instead, it is caused by the kidneys’ inability to reabsorb cystine that is filtered by the glomerulus.

Cystinuria

Cystinuria Cyanide-nitroprusside test 🧪 • Reduction of cystine by sodium cyanide → Addition of nitroprusside → Produces a red-______color in urine containing excess cystine. • False-positive results may occur in the presence of ketones and homocysteine.

purple

Cystine builds up as crystals in: • Cornea 👁️ • Bone marrow 🦴 • Lymph nodes 🦠 • Internal organs 🏥

Cystinosis

Cyanide-nitroprusside test: • 🧪 Positive for both…

homocystinuria and cystinuria

Silver-nitroprusside test: • 🧪 Specifically detects…

homocystinuria (only homocysteine reacts).