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Enzyme Deficiencies

Terms in this set (18)

Glycolytic Enzyme Deficiency
Associated with hemolytic anemia by decreaseing activity of Na/K ATPase leading to RBC swelling and lysis
Due to deficiencies in pyruvate kinase (95%), phosphoglucose isomerase (4%) - G6P to F6P, and other glycolytic enzymes
RBCs metabolize glucose anaerobically so depend solely on glycolysis
Pyruvate Dehydrogenase Deficiency
Causes backup of substrate (pyruvate and alanine) leading to lactic acidosis; can be congenital or acquired (e.g. in alcoholics due to B1 deficiency)
Findings: neurological defects
Treatment: increased intake of ketogenic nutrients (high fat content or increased lysine and leucine)
Lysine and leucine - the only purely ketogenic amino acids
Deficiency of Key Gluconeogenic Enzymes
Causes hypoglycemia
These enzymes include PC, PEPCK, F16BP, and G6P
Glucose-6-Phosphate Dehydrogenase Deficiency
Rate limiting enzyme in HMP shunt (which yields NADPH) - necessary to keep glutathione reduced
Glutathione detoxifies free radicals and peroxides, so decreased NADPH in RBC's causes hemolytic anemia due to poor RBC defense against oxidizing agents (fava beans, sulfonamides, primaquine) and anti-TB drugs
More prevalent among blacks
Creates Heinz bodies - altered hemoglobin precipitates w/in RBCs
Bite cells result from the phagocytic removal of Heinz bodies from macs
X linked recessive disorder; increases malarial resistance
Fructose Intolerance
Hereditary deficiency of aldolase B (recessive)
F1P accumulates, decreasing available phosphate and inhibiting glycogenolysis and GNG
Symptoms include hypoglycemia, jaundice, cirrhosis and vomiting
Treated with decreased intake of fructose and sucrose (fructose + glucose)
Essential Fructosuria
Involves a defect in fructokinase - benign and asymptomatic condition (since fructose doesn't enter cells)
Fructose appears in blood and urine
Galactosemia
Absence of galactose-1 phosphate uridyltransferase - autosomal recessive
Damage caused by accumulation of toxic substances (including galactitol) rather than absence of an essential compound
Cataracts, hepatosplenomegaly, mental retardation
Treated by excluding galactose and lactose (galactose + glucose) from the diet
Galactokinase Deficiency
Causes galactosemia and galactosuria, galactitol accumulation if galactose is present in the diet
Lactase Deficiency
Age dependent or hereditary intolerance (blacks, Asians) - due to loss of brush border enzyme
Causes bloating, cramps, and osmotic diarrhea - is treated by avoiding milk or using lactase pills in the diet
Hyperammonemia
Acquired (liver disease) or hereditary (ornithine transcarbamoylase deficiency)
Excess NH4+ depletes α-ketoglutarate, leading to inhibition of the TCA cycle - treated with benzoate or phenylbutyrate to lower serum ammonia levels
Ammonia intoxication leads to tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
Phenylketonuria
Decreased phenylalanine hydroxylase or tetrahydrobiopterin cofactor
Tyrosine becomes essential and phenylalanine builds up (since the essential a.a. phenylalanine is converted to tyrosine), leading to exkcess phenylketones in the urine
Causes mental retardation, growth retardation, fair skin, eczema and a musty body odor (b/c it's a disease of aromatic amino acid metabolism)
Treated by decreasing phenylalanine (in aspartame- nutrasweet), and increasing tyrosine in the diet
Alkaptonuria (onchronosis)
Congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine
Resulting alkapton bodies cause urine to turn black on standing; also the CT is dark - it is benign but may cause debilitating arthralgias
Albinism
Congenital deficiency of either tyrosinase (inability to synthesize melanin from tyrosine) - autosomal recessive; or, defective tyrosine transporters (decreased amounts of tyrosine and therefore melanin)
Can result from a lack of migration of neural crest cells
Lack of melanin increases the risk of skin cancer
Variable inheritance due to locus heterogeneity
Homocystinuria
3 forms all autosomal recessive - all result in excess homocysteine (so cysteine becomes essential) - can cause mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), and atherosclerosis (stroke and MI)
1. Cystathionine synthase deficiency - treatment: decrease Met and increase Cys and B12 in the diet
2. Decreased affinity of cystathionine synthase for pyridoxal phosphate (treated by greatly increasing B6 in the diet)
3. Homocysteine methyltransferase deficiency
Cystinuria
Common inherited defect of renal tubular amino acid transporter for cysteine, ornithine, lysine and arginine in the PCT of the kidneys; Excess cysteine in urine can lead to the precipitation of cysteine kidney stones (staghorn calculi); Treated w/acetazolamide to alkalinize the urine; Cysteine is made by 2 cysteines linked by a disulfide bond
Maple syrup urine disease
Blocked degredation of branched amino acids (Isoleucine, Leucine and valine) due to decreased α-ketoacid dehydrogenase
Causes increased α-ketoacids in the blood (especially leu)
Causes severe CNS defects, mental retardation and death
Adenosine Deaminase deficiency
Can cause SCID - severe combined (T and B) immunodeficiency disease - usually in kids (boy in the bubble)
Excess ATP and dATP imbalances the nucleotide pool via feedback inhibition of ribonucleotide reductase which prevents DNA synthesis and decreases lymphocyte count - it is the 1st disease to be treated by experimental human gene therapy
Lesch-Nyhan Syndrome
Purine salvage problem due to absence of HGPRT (converts hypoxanthine to IMP and guanine to GMP)
X-linked recessive leads to excess uric acid production
Findings include retardation, self mutilation, aggression, hyperuricemia, gout and choreoathetosis
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