Disorders of Metabolism Flashcards Preview

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Flashcards in Disorders of Metabolism Deck (42):
1

Pyruvate dehydrogenase complex (PDH) deficiency

X-linked; buildup of pyruvate shunted to lactate and alanine;
neurologic defects, lactic acidosis, increased serum alanine starting in infancy

2

Electron Transport Chain inhibitors (blocks ATP synthesis) & Uncoupling agents (produce heat)

Complex I: Rotenone
Complex III: Antimycin A
Complex IV: Cyanide, CO, Azide
ATP synthase (Complex V): Oligomycin
Uncoupling agents: 2,4-dinitrophenol, aspirin, thermogenin

3

G6PD deficiency

decreased NADPH in RBCs; most common human enzyme def.
hemolytic anemia, Heinz bodies (denatured Hb), Bite cells

4

Essential fructosuria

defect in fructokinase;
benign, fructose in blood and urine

5

Fructose intolerance

deficiency in aldolase B;
Fructose-1-P accumulates which inhibits gycogenolysis and gluconeogenesis;
hypoglycemia, jaundice, cirrhosis, vomiting

6

Galactokinase deficiency

deficiency in galactokinase, galactitol accumulates;
galactose in blood and urine, infantile cataracts, failure to track objects or develop social smile

7

Classic galactosemia

absence of galactose-1-P uridyltransferase;
failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability, can lead to E. coli sepsis in neonates

8

Lactase deficiency

stool has decreased pH and breath has increased Hydrogen w/ lactose tolerance test; normal mucosa in pts with hereditary lactose intolerance

9

essential glucogenic amino acids

Met, Val, His

10

essential glucogenic/ketogenic amino acids

Ile, Phe, Thr, Trp

11

essential ketogenic amino acids

Leu, Lys

12

acidic amino acids

neg charge;
Aspartate, Glutamate

13

basic amino acids

Arg, Lys, His

14

amino acids for growth

Arg, His

15

amino acids in histones

Arg, Lys

16

N-acetylgutamate deficiency

required cofactor for Carbamoyl phosphate synthetase I (Urea cycle);
leads to hyperammonemia;
in neonates: poorly regulated respiration and body temp, poor feeding, developmental delay, intellectual disability (identical presentation as in carbamoyl phosphate synthetase I def.)

17

Ornithine transcarbamylase deficiency (OTC)

most common urea cycle disorder (only X-linked urea cycle disorder, others are AR);
excess carbamoyl phosphate converted to orotic acid;
increased orotic acid in blood and urine, decreased BUN, sx of hyperammonemia, NO megaloblastic anemia (vs. orotic aciduria);
infant is lethargic, poorly feeding, poorly controlled breathing and body temp

18

PKU

disorder of aromatic amino acid metabolism leads to musty body odor;
screening occurs 2-3 days after birth (normal at birth b/c of maternal enzyme during fetal life)

19

Maple syrup urine disease

decreased alpha-ketoacid dehydrogenase (B1) causes incrased alpha ketoacids in blood, blocks degradation of Isoleucine, Leucine, Valine;
CNS defects, intellectual disability, death

20

Alkaptonuria (ochronosis)

deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate leading accumulation of homogentisic acid in tissue;
dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air, may have debilitating arthralgias

21

Homocystinuria

d/t: 1) Cystathionine synthase def. 2) decreased affinity of cystathionine synthase for pyridoxal phosphate (B6) 3) Homocysteine methyltransferase (methionine synthase) def.;
increased homocysteine in urine, intellectual disability, osteoporosis, MARFANOID HABITUS, kyphosis, len subluxation (downward and inward), thrombosis, atherosclerosis

22

Cystinuria

defect of renal PCT and intestinal amino acid transporter preventing reabsorption of Cysteine, Ornithine, Lysine, Arginine (COLA);
urinary cyanide-nitroprusside test is diagnostic

23

Von Gierke disease (Type I)

Glucose-6-phosphatase def.

24

Pompe disease (Type II)

Lysosomal alpha-1,4-glucosidase (acid maltase) def.

25

Cori disease (Type III)

Debranching enzyme (alpha-1,6-glucosidase) def.

26

McArdle disease (Type V)

skeletal muscle Glycogen phosphorylase (myophosphorylase) def.

27

Andersen's disease (Type IV)

Glycogen debranching enzyme def.

28

Hers disease (Type VI)

hepatic Glycogen phosphorylase def.

29

Fabry disease

alpha-galactosidase A def.;
Ceramide trihexoside accumulates

30

Gaucher disease

Glucocerebrosidase def.;
glucocerebroside accumulates

31

Niemann-Pick disease

sphingomyelinase def.;
sphingomyelin accumulates

32

Tay Sachs disease

Hexosaminidase A def.;
GM2 ganglioside accumulates

33

Krabbe disease

Galactocerebrosidase def.;
Galactocerebroside, psychosine accumulate

34

Metachromatic leukodystrophy

Arylsulfatase A def.;
Cerebroside sulfate accumulates

35

Hurler syndrome

alpha-L-iduronidase def.;
Heparan sulfate, dermatan sulfate accumulate

36

Hunter syndrome

Iduronate sulfatase def.;
Heparan sulfate, dermatan sulfate accumulate

37

Systemic Primary Carnitine deficiency

defect in tranport of LCFAs into mitochondria leads to toxic accumulation;
weakness, hypotonia, hypoketotic hypoglycemia

38

Medium chain acyl-CoA dehydrogenase deficiency

decreased break down of FAs into acetyl-CoA leads to accumulation of 8-10 carbon fatty acyl carnitines in blood and hypoketotic hypoglycemia;
may present in infancy or early childhood w/ vomiting, lethargy, seizures, coma, liver dysfunction

39

Hyperchylomicronemia (Type 1)

LPL def. or altered apolipoprotein C-II;
elevated Chylomicrons, TG, Cholesterol

40

Familial Hypercholesterolemia (Type IIa)

absent or defective LDL receptors;
elevated LDL, cholesterol

41

Hypertriglyceridemia (Type IV)

hepatic overproduction of VLDL;
elevated VLDL, TG

42

Abetalipoproteinemia

decreased synthesis of apolipoprotein B leads to inability to generate chylomicrons, decreased cholesterol and VLDL secretion into blood thus fat accumulates in enterocytes