Biochem pathways Flashcards
ADA deficiency enzyme
adenosine deaminase - for degradation of adenosine and deoxyadenosine
- leads to build up of dATP
ADA deficiency clinical
- toxic to lymphocytes
- leads to SCID
Lesch-nyhan enzyme
- absent HGPRT (converts hypoxanthine to IMP and guanine to GMP)
- excess of uric acid and de novo purine synthesis
Lesch-Nyhan clinical
intellectual disability, self-mutilation, aggression, hyperuricemia, orange in diaper, gout, dystonia
Duchenne protein
deleted dystrophin (frameshift)
Duchenne clinical
weakness in pelvic girdle, pseudohypertrophy of calves, waddling gait, early onset, dilated cardiomyopathy
Becker protein
deleted dystrophin (non-frameshift)
Becker clinical
same as Duchenne but less severe
myotonic type 1 gene
CTG trinucleotide repeat of DMPK gene (myotonin protein kinase)
myotonic type 1 clinical
myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia
fragile X gene
FMR1 gene (hypermethylation and less expression of X)
fragile X clinical
intellectual disability, autism, macroorchidism pot puberty, long face with large jaw, large everted ears, mitral valve prolapse
Edwards gene
trisomy 18
Edwards clinical
prominent occiput, rocker bottom feet, intellectual disability, nondisjunction, clenched fists, low set ears, micrognathia, congenital heart disease
- low PAPP-A and HCG
Patau gene
trisomy 13
Patau clinical
intellectual disability, microphthalmia, microcephaly, cleft lip and palate, holoprosencephaly, polydactyly, cutis aplasia, heart disease
cri-du-chat gene
microdeletion of short arm of chromosome 5
cri-du-chat clinical
microcephaly, moderate to severe intellectual disability, high pitched crying, epicanthal folds VSD
Williams syndrome gene
microdeletion of long arm of chromosome 7
Williams clinical
elfin facies, intellectual disability, hypercalcemia, well developed verbal skills, extreme friendliness, cardiovascular problems
Hartnup problem
deficiency in tryptophan transporter (can’t form niacin)
Hartnup clinical
pellagra like symptoms, diarrhea, dementia and dermatitis
G6PD deficiency enzyme
glucose 6 phosphate dehydrogenase (converts glucose 6 phosphate to produce NAPDH and glutathione)
G6PD clinical
- X linked recessive
- Heinz bodies due to precipitated hemoglobin
- bite cells due to splenic removal of macrophages
essential fructosuria enzyme
defect in fructokinase (converts fructuose to fructose 1P)
essential fructosuria clinical
- fructose can not get trapped in cells
- benign condition
- fructose appears in blood and urine
fructose intolerance enzyme
aldolase B (converts fructose 1-P to DHAP and glyceraldehyde)
fructose intolerance clinical
- fructose 1P accumulates leading to less free phosphate
- occurs after eating fruit, juice or honey
- reducing sugar in urine
- hypoglycemia, jaundice, cirrhosis, vomiting
galactokinase deficiency enzyme
galactokinase (converts galactose to galactose 1P)
galactokinase clinical
- mild condition
- galactose appears in blood and urine
- infantile cataracts and no social smile
classic galactosemia enzyme
defect in galactose 1P uridyltransferase (build up of galactose 1P)
classic galactosemia clinical
- galactitol builds up in lens of eye
- failure to thrive, jaundice, hepatomegaly, infantile cataracts, intelletual disability, ecoli sepsis
lactase deficiency clinical
- stool is lower pH, and breath shows high hydrogen content with lactose hydrogen breath test
- bloating, cramps, flatulence, osmotic diarrea
hyperammonemia defect
- excess of NH3 depletes alpha-ketoglutarate, inhibits TCA cycle
hyperammonemia clinical
tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
ornithine transcarbamylase deficiency enzyme
- X linked recessive
- converts ornithine to citrulline
- build up of ammonia, carbamoyl phosphate and orotic acid
ornithine transcarbamylase deficiency clinical
- increase in orotic acid in blood and urine
- low BUN
- symptoms of hyperammonemia
- no megaloblastic anemia (seen in orotic aciduria)
arsenate enzyme
inhibits lipoic acid (blocking pyruvate dehydrogenase)
arsenate clinical
vomiting, rice-water stools, garlic breath, QT prolongation
pyruvate dehydrogenase deficiency enzyme
build up of pyruvate leads to increase in lactate and alanine
pyruvate dehydrogenase deficiency clinical
- neurologic defects, lactic acidosis, increase in alanine
- treat with lysine and leucine (ketogenic amino acids)
phenylketonuria enzyme
- due to lack of phenylalanine hydroxylase or lack of tetrahydrobiopterin (BH4)
- leads to build up of phenylalanine and phenyl ketones in urine
- requires tyrosine (later step)
phenylketonuria clinical
- intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor
- aromatic AA disorder leads to musty odor
- avoid aspartame
maple syrup urine disease enzyme
- blocked degradation of branched amino acids (isoleucine, leucine and valine)
- less branched chain alpha ketoacid dehydrogenase (B1)
- increased ketoacids in blood
maple syrup urine disease clinical
- vomiting, poor feeding, urine smells like maple syrup or burnt sugar
- severe CNS defects, intellectual disability
- treat with ILV restriction and thiamine supplementation
alkaptonuria enzyme
- deficiency of homogentisate oxidase
- used in tyrosine degradation pathway (homogentisic acid goes to fumarate to TCA)
- build of of homogentisic acid
alkaptonuria clinical
- blue/black connective tissue, ear cartilage and sclera, urine turns black in air, debilitating arthralgias
homocystinuria enzyme
- cystathionine synthase deficiency (treat with less methionine, more cystine, B6, B12 and folate
- less affinity for cystathionine synthase for B6 (treat with B6 and cysteine)
- methionine synthase deficiency (give methionine)
- bottom line is an excess in hmocysteine
homocystinuria clinical
- osteoporosis, marfanoid, ocular changes, CV effects, stroke/MI, kyphosis, intellectual disabilities
cystinuria enzyme
- defect in transporter in kidney and gut that prevent reabsorption of cystine, ornithine, lysine and arginine (COLA)
cystinuria clinical
- cystine crystals in kidney
- treat with urine alkalinization and chelating agents
Von Gierke disease enzyme
- type 1 defect in glucose-6-phosphatase (converts G6P to glucose)
- impaired gluconeogenesis and glycogenolysis
Von Gierke disease clinical
- increase in glycogen, high blood lactate, high triglycerides, high uric acid and hepatomegaly (glucose can’t be freed)
- avoid fructose and galactose, treat with glucose
Pompe disease
- type 2 defect in lysosomal acid alpha 1-4 glucosiadase with alpha 1-6 glucosidase activity (acid maltase)
- can’t free glucose from small pieces of glycogen
Pompe disease clinical
- pompe trashes the pump
- cardiomegaly, hypertrophic cardiomyopathy, hypotonia, exercise intolerance, early death
Cori disease enzyme
- debranching enzyme
- cant free branched glucose from glycogen
Cori disease clinical
- gluconeogenesis is intact
- mild form of Von Gierke’s (normal blood lactate)
McCardle disease enzyme
- skeletal muscle glycogen phosphorylase
- muscles can’t use glycogen
McCardle disease clinical
- high glycogen in muscle, painful muscle cramps, myoglobinuria with exercise, arrhythmia form electrolyte abnormalities
- blood glucose is unaffected (only muscles)
carnitine deficiency enzyme
- carnitine transport of LCFA into mitochondria
carnitine deficiency clinical
- weakness, hypotonia and hypoketotic hypoglycemia
medium chain acyl-CoA dehydrogenase enzyme
- can’t break down medium chain FAs
- accumulation of fatty acyl carnitines in blood with hypoketotic hypoglycemia
medium chain acyl-CoA dehydrogenase clincial
- vomiting, lethargy, seizures, coma, liver problems
- can lead to sudden death in infants
- avoid fasting
abetalipoproteinemia enzyme
- deficiency in ApoB48 and ApoB100
- lack of chylomicrons, VLDL and LDL
abetalipoproteinemia clincal
- severe fat malabsorption, steatorrhea, failure to thrive
- later retinitis pigmentosa, spinocerebellar degeneration due to vitamin E, progressive ataxia, acanthocytosis
type 1 hypercholesterolemia enzyme
- lipoprotein lipase of apolipoprotein C-II deficiency
- increase in chylomicrons, TG, cholesterol in blood
type 1 hypercholesterolemia clinical
- eruptive/pruritic xanthomas
- pancreatitis, hepatosplenomegaly
- no risk for atherosclerosis
- cream layer in supernatant
type 2 familial hypercholesterolemia enzyme
no LDL receptors
- build up of LDL and cholesterol
type 2 familial hypercholesterolemia clinical
- tendon xanthomas
- accelerated atherosclerosis and corneal arcus
type 3 dysbetalipoproteinemia enzyme
- defective ApoE
- increase in chylomicrons and VLDL
type 3 dysbetalipoproteinemia clinical
- tuberoeruptive xanthomas and xanthoma striatum palmare
- premature atherosclerosis
type 4 hypertriglyceridemia enzyme
- hepatic overproduction of VLDL
- increase in VLDL and TG in blood
type 4 hypertriglyceridemia clinical
- hypertriglyceridemia can cause acute pancreatitis
