Biochemistry Block 3 Diseases
Terms in this set (99)
Describe Hyaline Membrane Disease. What are other names for it?
Respiratory distress syndrome
Premature infants have low lung surfactant production, glucocorticoids that stimulate DPPC synthesis can be given to reduce the possibility of this in premature infants
What is the biochemical basis for hyaline membrane disease?
Decreased amounts of lung surfactant component dipalmitoyl-phosphatidylcholine (DPPC)
What causes paroxysmal nocturnal hemoglobinuria?
a deficiency in glycosyl phosphatidylinositol (GPI) in hematopoietic cells
What kind of disease is paroxysmal nocturnal hemoglobinuria? What is its biochemical basis?
Loss of protein anchoring allows RBC hemolysis by complement system
What is the deficiency that causes Niemann pick disease?
Describe the Type A form of Niemann Pick disease
-large accumulation of sphingomyelin and phosphatidylcholine in liver and spleen
-loss of function complete
-severe mental retardation (neurodegeneration) and death in early childhood from rupture of lysosomes and cell death as a result
Describe the Type B form of Niemann Pick disease
Later onset, less severe, still have some activity
What causes ganglioside GM2 accumulation?
tay sachs disease
What is the enzyme deficiency in tay sachs disease?
What is the primary organ involved in tay sachs disease?
What disorder causes glucocerebroside accumulation?
What is the enzyme deficiency in gaucher disease?
What is the organ involvement in gaucher disease?
brain, liver, spleen
What disease causes ceramic trihexoside accumulation?
fabry disease (x-linked)
What is the enzyme deficiency in fabry disease?
What is the organ involvement in fabry disease (x-linked)
What disease causes sphingomyelin accumulation?
niemann pick disease
What is the enzyme deficiency in niemann-pick disease?
What is the organ involvement in niemann-pick disease?
brain, liver, spleen
What disease causes ceramide accumulation?
What is the enzyme deficiency in farber disease
what is the organ involvement in farber disease?
joints, liver, spleen
What causes cholelithiasis (broad)?
secretion of excess cholesterol into the bile by the liver when not accompanied by sufficient phospholipid and bile salts. Cholesterol precipitates forming gallstones
What are the causes of cholelithiasis?
malabsorption of bile acids from the intestine, obstruction of biliary tract, liver dysfunction, excess feedback inhibition of bile acid synthesis
What is the treatment for cholelithiasis?
removal of gallbladder or treatment with chenodeoxycholic acid
What deficiency causes familial type III hyperlipoproteinemia or familial dysbetalipoproteinemia or broad beta disease? What does it cause?
deficiency in apo E
high blood level of chylomicron remnants and IDLs
high cholesterol and atherosclerosis
What deficiency causes type II hyperlipidemia or familial hypercholesterolemia?
deficiency in LDL receptors
What is the result of type II hyperlipidemia or familial hypercholesterolemia?
can't take up chylomicrons in liver, have heart attacks and cardiovascular problems
What is deficient in Tangier disease?
ATP-binding cassette A1 transport protein (ABCA1)
How does lipoprotein (a) cause heart disease?
similar to LDL
apo (a) is linked to APOB100
structurally similar to plasminogen, contributes to increased heart disease by competing with binding of plasminogen to fibrin
slows down dissolution of clots
What does 3-beta-hydroxysteroid dehydrogenase deficiency cause?
no steroid hormones are produced
marked salt excretion in urine
all have female genitalia
What does lipoid congenital adrenal hyperplasia cause? What enzymes can be deficient to cause this?
steroidogenic acute regulatory protein (Star) or desmolase
nearly complete loss of steroid production
What does 17-alpha-hydroxylase deficiency cause?
virtually no sex hormones or cortisol
sodium and fluid retention leading to hypertension
all have female genitalia
What does 21-alpha-hydroxylase deficiency cause biologically?
masculinization of external genitalia of females
early virilization in males
Hirsuitism, short stature, early bone fusion
What does 21-alpha-hydroxylase deficiency cause biochemically?
glucocorticoids and mineralocorticoids completely absent or deficient, androgens overproduced
21-alpha-hydroxylase deficiency is the most common form of ___?
congenital adrenal hyperplasia
What are the biochemical results of 11-beta-hydroxylase deficiency?
decreased cortisol, aldosterone, corticosterone, increased deoxycorticosterone
What are the biological results of 11-beta-hydroxylase deficiency?
masculinization of external genitalia in females
early virilization in males
What happens in Addison disease?
low steroid hormone production
What happens in cushing's disease?
elevated ACTH and steroid hormone production
What happens in primary intestinal enteropeptidase (enterokinase) deficiency?
-deficiency in pancreatic secretion
-digestion of fats and proteins is incomplete
-abnormal appearance of lipids (steatorrhea) and proteins in the feces
What is cystinuria?
-defects in a transport system of the proximal tubule of the kidney which decreases reabsorption of basic AA cysteine, ornithine, arginine, lysine (COAL)
-inability to reabsorb cysteine leads to accumulation and precipitation of stones of cysteine in the urinary tract
What can help to treat cystinuria?
methionine restricted in diet, can be converted to cysteine
What causes Hartnup disorder?
the transport of tryptophan
What are the two major types of hyperammonemia?
acquired hyperammonemia (liver disease, alcoholism, hepatitis)
hereditary hyperammonemia (genetic deficiency of any of the 5 enzymes of the urea cycle)
What happens in acquired hyperammonemia?
-liver is damaged and can't make urea so ammonia goes up!
-BUN (blood urea nitrogen) goes down
-high ammonia is toxic to CNS and causes neurological complications, coma, death
What happens in hereditary hyperammonemia?
genetic deficiencies of urea cycle enzymes lead to hyperammonemia
What does ornithine transcarbamoylase deficiency cause? (6)
low blood arginine
undetectable blood citrulline
elevated blood ammonia
elevated blood glutamine
elevated orotic acid
What is the error causing hyperinsulinism/hyperammonemia syndrome?
effect of mutation is gain of function on enzyme
What is the defective enzyme in hyperinsulinism/hyperammonemia syndrome?
glutamate dehydrogenase-higher activity = hyperammonemia
What happens in hyperinsulinism/hyperammonemia syndrome?
-higher activity of glutamate dehydrogenase causes more glutamate to be converted to alpha ketoglutarate to create more glucose = hyperinsulinism
-cellular glutamate concentration decreases, results in reduced formation of NAG, reduced urea synthesis = hyperammonemia
What are treatments for hyperammonemia? (4)
-N-carbamylglutamate: analog of N-acetylglutamate that can activate CPS1
-ammonia scavenging drugs-phenylbutyrate-conjucates to glutamine
-benzoate-binds to glycine
-arginine supplements-arginine becomes essential AA
What genetic deficiencies cause folate deficiency?
methylene THF reductase deficiency
THF methyltransferase deficiency
What causes histidinemia?
mutation in the gene coding for histidase
What is elevated in histidinemia?
histidine levels in the blood and urine
What are the effects of histidinemia?
typically causes no health problems
What is the deficiency that causes maple syrup disease?
deficiency in branched chain alpha keto dehydrogenase that decarboxylates leucine, valine, and isoleucine
What is the result of maple syrup disease?
results in accumulation of AA and their keto acids, this interferes with brain functions and is characterized by feeding problems, vomiting, dehydration, severe metabolic acidosis and characteristic maple syrup odor to the urine
What makes up the branched chain keto dehydrogenase enzyme complex?
a heterotetrameric branched chain alpha keto acid decarboxylase (E1)
a dihydrolipoyl transacylase (E2)
a dihydrolipoamide dehydrogenase (E3)
What deficiency causes CLASSICAL maple syrup disease specifically?
E3 component (dihydrolipoamide dehydrogenase), causes entire complex to stop working
What does methylmalonyl coA mutase deficiency result in?
elevated levels of methyl malonyl CoA in the blood
metabolic acidosis and developmental problems occur
How does homocysteine cause vascular disease?
promotes oxidative damage
endothelial dysfunction via inhibition of collagen, elastin, and proteoglycans
these are risk factors for occlusive vascular diseases
What is the enzyme deficiency in cystathioninuria?
What does cystathioninuria cause?
accumulation of cystathione and its metabolites
What is homocystinuria a deficiency in?
cystathionine beta synthase
What does homocystinuria cause?
accumulation of homocysteine in the urine
methionine/its metabolites are elevated in the blood
mental retardation, osteoporosis, myocardial infarction, dislocation of the lens
What is the enzyme deficiency in oxaluria type I?
liver peroxisomal enzyme alanine: glyoxylate-aminotransferase (AGT) which converts glyoxylate to glycine
What are the results of oxaluria type I?
kidney stones from calcium oxalate buildup
What is the enzyme deficiency in tyrosinemia II?
What does tyrosinemia II affect?
eyes, skin, mental development
What is the enzyme deficiency in alkaptonurea?
What are the symptoms of alkaptonurea?
black colored urine
can cause cartilage damage, arthritis, kidney stones
What is the enzyme deficiency in tyrosinemia I?
What does tyrosinemia I cause?
liver failure, jaundice, cabbage like odor
What is the enzyme deficiency in classical phenylketonuria?
What is the enzyme deficiency in non-classical phenylketonuria?
defects in BH4 synthesis
What results from phenylketonuria?
accumulation of phenylalanine and deficiency of tyrosine
Hyperphenylalaninemia can also be caused because of deficiency of any enzymes needed to synthesize BH4 or BH2
What are the symptoms of PKU?
mental retardation, failure to walk/talk, microcephaly
CNS symptoms due to elevated levels of metabolites that interfere with AA transport into the brain
What is Parkinson's disease caused by?
defective production of DOPA
What is the enzyme defect in albinism?
tyrosinase which is required for the production of melanin
What are the forms of albinism?
oculocutaneous and ocular albinism
What are the symptoms of albinism?
lack of pigmentation
nystagmus (involuntary eye movements)
strabismus (crossed eyes)
amblyopia (lazy eye)
What defects cause porphyrias?
defects in heme synthesis from enzyme defects leading to the accumulation of tetrapyrrole intermediates
What is the result of having porphyrias in general?
accumulation and increased excretion of porphyrins or porphyrin precursors, get purple color in urine
What are the two main kinds of porphyrias?
How can porphyrias lead to photosensitivity?
porphyrin mediated formation of superoxide radicals oxidatively damages membranes and causes the release of destructive enzymes from lysosomes-this destruction of cellular components can cause photosensitivity
What symptoms can result from porphyrias?
neurological symptoms from autonomic neuropathy
cutaneous symptoms from photosensitization
urinary symptoms-discolored urine under UV light
Increased ALA synthase activity is a common feature of ___ and is caused by decreased ___
decreased heme synthesis because you are increasing the production of intermediates and never getting to heme in the pathway
What is an example of an acquired porphyria?
What occurs in lead poisoning?
inhibition of ferrochelatase or ALA dehydrates displaces Zn2+ at the active site and causes mental symptoms/abdominal pain in adults
What is the enzyme deficiency in Crigler-Naiiar I/II and Gilbert Syndrome?
bilirubin glucuronyl transferase
What protein deficiency results in Dubin-Johnston syndrome?
multiple drug-resistance protein 2 that is responsible for the transport of conjugated bilirubin out of the liver
What causes jaundice?
-deposition of bilirubin secondary to increased bilirubin in the blood-symptom of underlying disorder!
-yellow color of skin, nail beds, and sclerae
What are the types of jaundice?
Describe hemolytic jaundice
-massive lysis of RBC caused as a result of sickle cell, pyruvate kinase or G6PDH deficiency can produce bilirubin faster than it can be conjugated
-more bilirubin excreted in bile, more enters enterohepatic circulation
-urinary urobilinogen increased
-unconjucated bilirubin is elevated in blood causing jaundice
Describe hepatocellular jaundice
-damage to liver cells can cause unconjugated bilirubin levels to increase in the blood as a result of decreased conjugation
-the bilirubin that IS conjugated isn't efficiently secreted into bile, but diffuses into the blood
-urobilinogen increased in urine because of decrease in enterohepatic circulation from the liver damage = more enters blood = filtered into urine
What are the symptoms of hepatocellular jaundice?
pale/clay colored stool
AST and ALT elevated in plasma
Describe obstructive jaundice
results from obstruction of the bile duct, preventing passage of bilirubin into the intestine
liver pours back conjugated bilirubin into the blood
Describe neonatal jaundice
decreased bilirubin glucuronyl transferases causes an increase in unconjugated bilirubin, treated with blue fluorescent light that converts bilirubin to more polar and more water soluble isomers that can be excreted without conjugation
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