Biochem - Metabolism (Amino Acid Derivatives & Associated Disorders) Flashcards
Pg. 110-112 in First Aid 2014 Sections include: -Amino acid derivatives -Catecholamine synthesis/tyrosine catabolism -Phenylketonuria -Alkaptonuria (ochronosis) -Homocystinuria -Cystinuria -Maple syrup urine disease
Draw the derivatives of phenylalanine in consecutive order, including the cofactors required to create them.
See p. 110 in First Aid 2014 for visual at top of page
Draw the derivatives of Tryptophan in consecutive order, including the cofactors required to create them.
See p. 110 in First Aid 2014 for visual at top of page
What substance is a derivative of Histidine? What cofactor is required for its synthesis?
Histamine; B6
What important substance is a derivative of Histidine? What cofactor is required in their synthesis?
Porphyrin => Heme; B6
What are 2 important derivatives of glutamate? Which requires B6 cofactor for its synthesis?
GABA, Glutathione; B6 for GABA synthesis
What are 3 important derivatives of arginine? Which of these requires BH4 cofactor for its synthesis?
Creatine, Urea, Nitric oxide; BH4 for Nitric oxide synthesis
What enzyme is affected in Alkaptonuria? What is the normal function of this enzyme?
Homogentisate oxidase: Homogentisic acid => Maleylacetoacetic acid; Note: Homogentistic acid is derived from Tyrosine (which is dervied from Phenylalanine) and Maleylacetoacetic acid feeds into the TCA cycle
What enzyme is affected in PKU? What is the normal function of this enzyme?
Phenylalanine hydroxylase: Phenylalanine => Tyrosine (using BH4 as cofactor)
What enzyme is affected in Albinism? What is the normal function of this enzyme?
Tyrosinase; DOPA (dihydroxyphenylalanine) => Melanine
What enzyme is inhibited by Carbidopa? What is the normal function of this enzyme?
DOPA decarboxylase: DOPA (dihydroxyphenylalanine) => Dopamine (using vitamin B6 as cofactor)
What factor in the catecholamine synthesis/tyrosine catabolism pathway is stimulated by cortisol? What effect does this have?
SAM (S-adenosylmethionine): Norepinephrine => Epinephrine
Draw the major products of the phenylalanine/tyrosine catabolism/catecholamine synthesis pathway.
See p. 110 in First Aid 2014 for visual near bottom of page
What are 2 causes of phenylketonuria? Which of these causes malignant PKU?
Due to decreased phenylalanine hydroxylase or decreased tetrahdrobiopterin cofactor (malignant PKU).
What amino acid becomes essential in patients with PKU?
Tyrosine becomes essential
What urine finding is associated with PKU, and what causes this?
Increased phenylalanine leads to excess phenylketones in urine
What are 6 clinical findings associated with phenylketonuria?
Findings: (1) Intellectual disability (2) Growth retardation (3) Seizures (4) Fair skin (5) Eczema (6) Musty body odor; Think: “disorder of AROMAtic amino acid metabolism => musty body ODOR”
What is the treatment of phenylketonuria?
Treatment: Low phenylalanine and High tyrosine in diet
What is of most concern with maternal PKU?
Lack of proper dietary therapy during PKU
What are 4 clinical findings in an infant affected by maternal PKU?
Findings in infant: (1) microcephaly (2) intellectual disability (3) growth retardation (4) congenital heart defects
What is the mode of inheritance of PKU? What is its incidence?
Autosomal recessive. Incidence ~ 1:10,000
When is PUK screened for, and why?
Screened for 2-3 days after birth (normal at birth because of maternal enzyme during fetal life)
What are 3 examples of phenylketones?
Phenylketones - (1) Phenylacetate, (2) Phenyllactate, and (3) Phenylpyruvate
What substance must PKU patients avoid, and why?
PKU patients must avoid the artificial sweetener aspartame, which contains phenylalanine
What is another name for Alkaptonuria?
Alkaptonuria (ochronosis)
What is Alkaptonuria (ochronosis)?
Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate
What is the mode of inheritance of Alkaptonuria? Is it a benign or malignant disease?
Autosomal recessive. Benign disease.
What are 4 clinical findings associated with Alkaptonuria?
Findings: (1) dark connective tissue, (2) brown pigmented sclerae, (3) urine turns black on prolonged exposure to air. May have (5) debilitating arthralgias (homogentisic acid toxic to cartilage).
What musculoskeletal finding may be present in patients in Alkaptonuria, and why?
May have debilitating arthralgias (homogentisic acid toxic to cartilage).
What is the mode of inheritance of all types of homocystinuria?
All autosomal recessive
What are 3 forms of homocystinuria? What do all forms have in common?
Types (all autosomal recessive): (1) Cystathionine synthase deficiency (2) Decreased affinity of cystathionine synthase for pyridoxal phosphate (3) Homocysteine methyltransferase (methionine synthase) deficiency; All forms result in excess homocysteine
What is the treatment for homocystinuria due to cystathionine synthase deficiency?
Treatment: low methionine, high cysteine, high B12 and folate in diet
What is the treatment for homocystinuria due to low affinity of cystathionine synthase for pyridoxal phosphate?
Treatment: very high B6 and high cysteine in diet
What is the treatment for homocystinuria due to homocysteine methyltransferase (methionine synthase) deficiency?
Treatment: High methionine in diet
What are 8 clinical findings associated with homocystinuria?
Findings: (1) very high homocysteine in urine (2) intellectual disability (3) osteoporosis (4) tall stature (5) kyphosis (6) lens subluxation (downward and inward) (7) thrombosis and (8) atherosclerosis (stroke and MI)
What ophthalmologic condition is associated with homocystinuria?
Lens subluxation (downward and inward)
What vascular condition is associated with homocystinuria? What are 2 complications that may arise?
Atherosclerosis (stroke and MI)
Draw the important reactions related to homocysteinuria, highlighting the 2 enzymes that may be affected to cause this disorder.
See p. 111 in First Aid 2014 for visual near bottom of page
What is the defect in cystinuria?
Hereditary defect in renal PCT and intestinal amino acid transporter for Cysteine, Ornithine, Lysine, and Arginine; Think: “COLA”
What urine finding occurs in cystinuria, and why?
Excess cysteine in urine can lead to precipitation of hexagonal cystine stones
What is the mode of inheritance of cystinuria? What is its incidence like?
Autosomal recessive. Common (1:7000)
What test is diagnostic for cystinuria?
Urinary cyanide-nitroprusside test
What is the treatment for cystinuria?
Treatment: urinary alkalinization (e.g., potassium citrate, acetazolamide) and chelating agents increase solubility of cystine stones; good hydration
Of what is cystine composed?
Cystine is made of 2 cysteines connected by a disulfide bond
What is the defect and metabolic effects of maple syrup urine disease?
Blocked degradation of branched amino acids (Isoleucine, Leucine, Valine) due to decreased alpha-ketoacid dehydrogenase (B1). Causes increased alpha-ketoacids in the blood, especially those of leucine; Think: “I Love Vermont MAPLE SYRUP from maple trees (with BRANCHES)”
What are 3 symptoms/conditions caused by maple syrup urine disease?
Causes severe CNS defects, intellectual disability, and death
What is the mode of inheritance of maple syrup urine disease?
Autosomal recessive
What describes the urine of patients with maple syrup urine disease?
Urine smells like maple syrup/burnt sugar
What is the treatment for maple syrup urine disease?
Treatment: restriction of leucine, isoleucine, and valine in diet, and thiamine supplementation
