Genetics Block 3
Card Set Information
Genetics Block 3
Genetics Block 3
What are the normal plasma levels of phenylalanine?
What are the levels in phenylketonuria?
Tetrahydrobiopterin is used by what enzymes?
Denovo synthesis of BH4 occurs from what molecule?
Classic PKU is caused by what mutation?
Smoking oxidizes what a.a in the active site of alpha 1 antitrypsin?
Why would a pt with PKU present with albinism?
BH4 is needed for tyrosine hydroxylase
Tyrosine is a precursor to melanin
What risk could high levels of phenylalanine pose to a fetus?
it could act as a teratogen
Alkaptonuria is caused by what deficiency?
Homogenistic acid oxidase deficiency
What happens in Alkaptonuria?
Dark connective tissue
What two conditions present with a cherry red macula?
Macrophages with crinkled paper tissue appearance result in what disease?
Prostoglandins, leukotrienes and thromboxanes are all derived from what fatty acid?
cyntathionine beta synthase (Vit B6--pyridoxal phosphate)
methionine synthase( folate, Vit B 12)
Which condition's symptoms resemble that of Marfan's?
Supplementation of vitamins in Homocystonuria is done for what purpose?
To prevent thrombogenicity
Whats deficient if Maple syrup disease?
branched chain alpha keto acid dehydrogenase
What a.a are not broken down in Maple Syrup Disease?
Leucine, Isoleucine, Valine
Which condition is "thiamine responsive"?
Maple Syrup Disease
Lesch-Nyhan syndrome is caused by a deficiency of what enzyme?
What is produced in excess in Lesch-Nyhan Syndrome?
Uric acid causing self mutilation, aggression,
Alpha 1 antitrypsin belongs to what family of protease inhibitors?
A deficiency of Alpha 1 antitrypsin causes what?
Whats an example of an ecogenetic disorder?
Alpha 1 antitrypsin
Alpha 1 antitrypsin causes damage in what two organs?
Liver and Lungs
Nicotine oxidizes what a.a in the alpha 1 antitrypsin?
methionine at 358
Acute intermittent porphyria is caused by a deficiency of what enzyme?
Why would events that induce cytochrome p 450 precipitate symptoms of acute inter
cholesterol in skin
cholesterol in arteries
What is the cause of Hyperlipoproteinemia Type IIa?
Deficient LDL receptor
Beta lipoprotein is what?
Alpha lipoprotein is ?
What makes up LDL?
cholesterol and cholesteroyl esters
What is the function of VLDL?
transport of TAG's from liver to tissues
B-100 is present on what FA molecule?
B-48 is a marker on what ?
Causes of HyperLipoproteinemia?
1. LDL receptor
2. B-100 apolipoprotein
3. ARH adapter protein
4. PCSK9 protease
Hypercholesterolemia results from what?
decreased or no LDL receptor
Type I Hyperchylomicronemia results from what?
deficient lipoprotein lipase or Apo C-II
TAG and Cholesterols
Type IV hypertriglyceridemia results from what?
Hepatic overproduction of VLDL
Abeta lipoproteinemia results in what?
Absent Apo-B100/ Apo-B48
Gene mutations that cause Hyperlipoproteinemia?
ARH adaptor protein
What is the function of ARH protein?
Anchors LDL receptor in the pit
What is a cofactor for lipoprotein lipase?
What enzyme catalyzes the esterification of cholesterol in HDL?
What enzyme degrades TAG's in Chylomicrons an VLDL?
LDL is also called?
A gain of mutation in the PCSK9 protease Gene results in what?
lower LDL receptor amounts
VLDL obtains Apo-c -II and Apo-E from what lipoprotein?
Transposition is responsible for what cholesterol disorder?
Pre beta lipoprotein is what?
Apo-B48 is needed for what?
To leave the intestinal cell
Chylomicrons acquire what from HDL?
Apo-C II and Apo-E
Carbon,1 ,2 and 3 carry what kinds of FA?
3--sat or unsat
What happens to glycerol after lipoprotein lipase creates in from the Chylomicron?
It goes to liver where it could
What happens to chylomicron remnant?
It is absorbed by the liver
What lipoproteins are translated in intestinal cells and liver?
Persistent chylomicrons in the blood suggest what?
deficient lipoprotein lipase
or Apo-C II
HTGL removes what?
remaining TAG from Chylomicrons
What is the problem in Niemann-Pick C?
lysosomes cant hydrolyze cholesterol esters
What does HDL do?
picks up cholesterol from tissues
What enzyme is used to trap cholesterol as cholesterol esters?
HDL uses what receptor on the liver?
scavenger B1 receptor
HDL carries what cofactor that activates LCAT?
What is exchanged between HDL and VLDL
cholesterol for TAG and Phosphatidylcholine
A1 does what in HDL
Cholesterol + macrophages make up what?
HMG coA reductase transforms HMG coA to what?
What is the purpose of NO in BV?
prevents platelet sticking to endothelium
Alu transposition may be responsible for what genetic diseases?
What type of collagen is defective in Osteogenesis imperfecta?
What is the mutation in Osteogenesis Imperfecta?
Glycine is substituted by a bulky amino acid
Type I of Osteogenesis Imperfecta is caused by what?
Decrease in Type I colagen
Prenatal diagnosis of Osteogenesis Imperfecta is accomplished how?
Whats responsible for Trinucleotide repeat expansions?
Slipped mispairing during DNA replication
unequal crossing over
Hypermutation of 5' UTR and promoter is responsible for which Trinucleotide repeat expansion disease?
Fragile X syndrome
In what disease is the trinucleotide repeat predisposes the individual for earlier onset of disease?
What complexes in the ETC need iron?
Severity and age of onset correlated with repeat number is characteristic of what Group of diseases?
Trinucleotide repeat expansion diseases
Myotonic Dystrophy type 2 is caused by what?
tetranucleotide repeat expansion
Example of a pleitropy disease?
What organ prefers ketone bodies?
The carbon skeleton left after deamination is used for what?
Glucogenic a.a should contribute what?
pyruvate or any component of TCA cycle
What a.a are purely ketogenic?
What is a bidirectional shuttle?
Why is ammonia present in urine
to maintain acid -base homeostasis
What a.a form glutamate via deamination?
What makes up Glutathione
2 amino transporters in the blood?
2 amino groups in urea come from where?
What a.a is involved in the formation of glycosidic bond of glycoproteins?
If folic acid is deficient what may be excreted in urine?
Folic acid is involved in what?
one carbon methabolism
Histamine is formed from what a.a?
Decarboxylation uses what coenzyme?
What gives rise to NO?
Creatinine present in plasma may suggest what?
Glycine is used for what?
Detoxification of benzoic acid
What is caused by deficiency of glycine cleavage complex?
What is the endogenous source of oxalate in the body?
What are the 2 sulfur containing amino acids?
What is the only reaction where all Pi from ATP are liberated?
Homocytynuria is caused by what?
cystathionine beta synthase
low vitamin b12
deficiency of cystathionine-methyl transferase
What membrane phospholipid gives rise to arachidonic acid?
PAPS gets its sulfate from where?
How are small amounts of cyanide detoxified?
Classical homocystynuria symptoms?
Elevated homocysteine in pregnant women are correlated with risk of what?
Neural tube defect
What is used for one carbon transfer?
SAM and Folate
Deficiency in Maple syrup Disease?
branched chain alpha ketoacid dehydrogenase
Which disease is "thiamine responsive"
Maple Syrup Disease
Most hereditary enzymatic deficiencies are inherited in what fashion?
Musty odor is characteristic of what disorder?
Albinism is inherited how?
Multiple inheritance pattern
Alkaptonuria is caused by?
homogenistic acid oxidase
part of tyrosine degradation pathway
Proteins rich in what amino acids are degraded rapidly?
HCL activates what enzyme?
pepsinogen to pepsin
a.a enter cells via what transporter?
Endopeptidase activates what?
What creates a Na +gradient in the intestinal cell?
What are the only a.a that are not metabolized by liver?
branched chain amino acids
What are the 2 transporters in the kidney and intestine?
COAL--cysteine, ornithine, arginine, lysine
kidney stone bc of high cystein in urine
defective COAL transporter
kidney stones due to high cysteine in the urine
Hartnup disorder symptoms?
deficiency of tryptophan
Transfer of an amino group from an a.a to an alpha keto glutarate is called?
What are the only 2 a.a that do not go thru transamination?
All transaminases require what vitamin?
Vit B6 pyridoxal phosphate
What enzyme produces free ammonium?
What activates glutamate dehydrogenase?
How is ammonia transported to the liver?
ammonia + glutamate= glutamine---> liver
ammonia + pyruvate = alanine ---> liver
What is the precursor of N in the Urea cycle?
aspartate from glutamate
NH3 from glutamate
Ornithine transcarbomylase deficiency?
makes citrulline from carbamoyl phosphate and ornithine
HOw much mutant mtDNA need to be present to cause disease from deletions?
Mitchondrial mutations affect what systems?
GI, PNS, CNS, Cardiac, renal endocrine
What is the most common mtDNA mutation
A to G on tRNA
Leber's Hereditary Optic Neuropathy symptoms
sudden onset of blindness in young adults
Alzheimers disease onset is in what age group?
6th-9th decade of life
amyloid precursor protein
docking of molecules to receptors
What carries APO E?
VLDL, LDL, IDL, chylomicrons
Deposits of sticky peptides cause what disease?
Tau protein is implicated in what disease?
Tau protein in Alzeimers is in what state?
beta APP is cut wrong by what protease
Sticky APP are found in what condition which results in plaques?
Cystinuria and cause what?
Cystinuria is caused by malabsorption of what a.a?
Diamino basic a.a malabsorption cause what condition?
cysteine crystals in lysosomes
Which a.a gives rise directly to ketone body?
Maple syrup disease is caused by?
deficiency of branched chain alpha keto acid dehydrogenase
Symptom of Maple syrup disease?
Burned sugar smell of urine
5 factors of dehydrogenases?
coenzyme a -b5
What enzyme converts pheneylalanine to tyrosine
Deficiency of phenylalanine hydroxylase or tetrahydrobiopterin causes what disease?
All transaminases require what coenzyme?
vit b 6 pyridoxal phosphate
Rate determining enzyme is ketone body synthesis?
HMG coa Synthase
Vitamin C is needed for what?
hydroxylation of lysine and proline in collagen
dopamne beta hydroxylase
What cells are present in the adrenal medulla?
What enzyme present in maloncytes converts tyrosine to DOPA?
Pheomelanin is what color?
Phenylketonuria is caused by what?
Reduction of dihydrobiopterin to tetrahydrobiopterin needs what?
Presence of what product in urine causes phenylketonuria
Disorder of aromatic a.a metabolism causes what ?
musty odor of urine
Why does urine turn yellow?
urobilinogen is oxidized by oxygen and turns yellow
Tyrosinemia is caused by?
high levels of tyrosine
Albinism is caused by?
many inheritance pattern
Deficiency of what enzyme causes Albinism?
Transamination of alanine produces what?
Pyridoxine phosphate is needed for what product of tryptophan metablism?
Xanthurenic acid accumulates in what condition
problem metabolism of tyrosine
Decarboxylation of a.a uses what a.a?
pyridoxal phosphate--vit b 6
What keeps tetrahydrobiopterin in reduced state?
Argentaffinoma is a cancer of what?
what does it produce?
argentaffin cells of abdominal cavity
What product is made in Argentaffinoma?
5 Hydroxy indole acetic acid
What produces NE?
Transporter defect of neutral amino acid..tryptophan causes what disease?
How is codeine activated?
Thru what mechanism?
via cyt p450
blocks RNA polymerase
Deficiency of NADPH Oxidase causes what?
Heparin blocks the synthesis of what factors?
Protein C and Protein S
Heme is degraded by what system?
reticulo endothelial system
If biliverdin reductase is absent what accumulates?
How is bilirubin transported?
by binding to albumin
What accepts the bilirubin from albumin in the hepatocyte?
How do hepatocytes make bilirubin polar?
by adding glucuronic acid to it via UDP glucuronyl transferase
What bacterial enzyme cleaves bilirubin to urobilinogen?
Stercobilinogen is also known as?
Normal product of Heme catabolism?
Causes for prehepatic Jaundice?
Phospholipase A 2
What is increased in hemolytic jaundice?
Urinary Urobilinogen is increased or decreased in hemolytic jaundice?
What is the deficiency in Gilbert's syndrome?
ALA synthase is used for what?
UDP glucuronyl transferase is used for what?
ALA synthase--heme synthesis
UDP glucuronyl transferase---solubility of bilirubin
Appearance of disease at an earlier stage
Mechanism for Tandem repeats?
Slipped mispairing during Replication
All tandem repeat diseases are maternally repeated except?
WHich tandem repeat disease is caused by tetra repeat?
Myotonic dystrophy 2
Where is the tandem repeat in
Mutation in intron of 5' UTR causes what?
decreased transcription via hypermethylation
What is the hallmark of Huntington
Consaguinity plays a role in which disease?
Cystic Fibrosis is on what gene?
Mutation in Cystic Fibrosis?
deletion of phenylalanine at 508
Bilateral absence of vas deferens is seen in what disease?
Meconium Ileus is see in what disease?
The CFTR channel has how many domains?
The CFTR genotype is a good predictor of the exocrine function but not of pulmonary function
What disease is Semi dominant?
Type IIa hypercholesterolemia is caused by?
defective LDL receptor
defective LDL uptake
What are the 4 causes for Type IIA
ARH adapter protein
Hypercholesterolemia is located on what gene?
Gain of function of what produces Type II a Hypercholesterolemia?
What mutation in PCSK9 causes lower cholesterol levels?
Which scavenger receptor takes up oxidized LDL in macrophages?
Scavenger Type A
What enzyme is elevated in DMD?
Why would a female have DMD?
bc of random x inactivation
Osteogenesis imperfecta affects which collagen?
What is the repeating unit in collage?
What are the 2 types of Osteogenesis Imperfecta?
Type I--decreased amount of collagen
Type -2----a.a substitution
WhAT Are the 3 proteins in which a mutation may cause Alzeimers?
Amyloid precursor protein
What kind of plaques are seen in alzeimers?
amyloid presinile plaques
Which secratase produces a neurotoxic amyloid precursor protein?
People with what trisome are predisposed to Alzeimers disease?
What is the relationship betwee APO E and Alzeimers?
Phytanic acid accumulates in what disease?
Kayser Fleisher ring is seen in what disease?
What is Menkes disease?
Copper is not released from cells
Elfin like facies and great interpersonal skills are present in what disease?
A third copy of what in pt with downsyndrome predisposes them to Alzeihmers?
Amyloid Precursor protein
The FMR-1 gene is found in what condition?
What is added to cholic acid and chenodeoxycholic acids to make them salts?
glycine and taurine
What is the rate determining step in the formation of cholic acid?
cholesterol 7 alpha hydroxylase
What inhibits cholesterol 7 alpha hydroxylase?
What promotes its actions?
Ornithine transcarbamylase results in high levels of what?
When does it usually present?
within first few days of life
Squalene monooxygenase is involved in what?
conversion of squalene to lanosterol
Wolman disease is caused by?
deficiency of breaking down of cholesterol esters
Niemann-Pick C is caused by?
failure of transport of cholesterol from lysosome to
What protein is deficient in Limb Girdle Dystrophy?
What proteins are deficient in Congenital Muscular dystrophy?
What protein is deficient in Emery-Dreyfus muscular dystrophy?
What are the autosomal recessive muscular dystrophies?
What is heteroplasmy?
more than one copy of a genome is a cell or individual
What are the 3 types of mutations in mtDNA?
What kind of mutation causes Pearson and Kearns syndrome?
MELAS is caused by a mutation where?
Chronic progressive external Opthalmoplegia is caused by what type of mutation?