Block 5 Flashcards
the endoplasmic reticulum is continuous with what structure
nuclear membrane
where is the site of protein and lipid synthesis
endoplasmic reticulum
what do ribosomes synthesize
proteins
what is the difference between what free and membrane bound ribosomes produce
free produce proteins mostly used by the cell
membrane bound produce proteins for secretion (ex: hormones, digestive enzymes)
where is the site of initiation of posttranslational modification of newly synthesized proteins
rough ER
where does lipid and steroid synthesis occur
smooth ER
where does cholesterol and lipoprotein synthesis occur
smooth ER
where does detoxification of drugs and toxins occur
smooth ER
what is the sarcoplasmic reticulum
smooth ER of muscle cells
what is the function of the sarcoplasmic reticulum
store calcium for muscle contraction
where is the location of glucose 6-phosphatase
smooth ER
what 3 enzymes of steroid synthesis are present in the mitochondria
cholesterol desmolase
17 alpha
11 beta
what enzyme of steroid synthesis is present in the smooth ER
21 beta
what is the rough ER of neurons called
nissl body
what is the function of nissl bodies
synthesize neurotransmitters
what is the main organelle involved in posttranslational modification
golgi
vesicles come in from the __ and leave from the __ golgi
(cis or trans)
enter through cis
leave through trans
what are 3 examples of posttranslational modification
glycosylation
hydroxylation (ex: collagen)
carboxylation (ex: vit K)
what are the 3 main functions of golgi modification
protect proteins from degradation
direct proteins to their target locations
allow protein recognition by receptors
do golgi modifications add N or O oligosaccharides
O
(“O” in the gOlgi)
where does mannose 6-phosphate get added to lysosomal proteins
golgi
N linked oligosaccharides are often attached to what amino acid
asparagine
where are N linked oligosaccharides synthesized
eNdoplasmic reticulum
where are O lined oligosaccharides synthesized
gOlgi
O linked oligosaccharides are often attached to what amino acid
serine or threonine
what is an example of O linked oligosaccharide
mucins
respiratory infection can cause mucin buildup. what can we say about the posttranslational modification which has occurred to produce the mucin
O linked glycosylation in the golgi
is mannose 6 phosphate added to N or O linked oligosaccharides
N
mannose 6 phosphate triggers packaging in trans golgi –> __
lysosomes
defective mannose 6 phosphate addition in the lysosomes can lead to what disease
I cell
what type of inheritance pattern is I cell disease
autosomeal recessive
what enzyme is deficient in I cell disease
N-acetylglucosaminyl-1-phosphotransferase
in I cell disease, since enzymes are not destined properly to the lysosomes, where do they end up
outside the cell
what is missing from the golgi as a result of I cell disease
hydrolases
for enzymes destined to the lysosomes, mannose is added in what organelle
phosphotransferase adds phosphate to the 6th position in what organelle
mannose= ER
6P= golgi
what is the defective enzyme of pompe’s disease
lysosomal alpha 1,4 glucosidase (acid maltase)
what are the symptoms of pompe’s disease
infant cardiomegaly and hypotonia
what type of inheritance is hurler syndrome
autosomal recessive
what type of inheritance is hunter syndrome
X linked
what type of inheritance are sanfilippo and sly syndrome
autosomal recessive
what enzyme is deficient in hunter syndrome
iduronate sulfatase
how can you differentiate hunter syndrome from hurler syndrome
hunter- no corneal clouding
hurler- corneal clouding
what enzyme is deficient in hurler syndrome
alpha L iduronidase
what is the enzyme missing in tay sachs
hexaminidase A
what buildsup in tay sachs
GM2
what are the 2 main symptoms of tay sachs
cherry red spot in macula
startle reflex
what enzyme is missing in gaucher disease
glucocerebrosidase
what builds up as a result of gaucher disease
glucocerebroside
what are the 2 main symptoms of gaucher disease
crumpled paper inclusions
erosion of bones/fractures
what enzyme is missing in niemann pick diease
sphingomyelinase
what builds up as a result of niemann pick disease
sphingomyelin
what are the 2 main symptoms of niemann pick disease
hepatosplenomegaly
foamy macrophages
what builds up in fabry disease
ceramide trihexoside
what enzyme is missing in fabrys disease
alpha galactosidase A
what inheritance pattern is fabrys disease
X linked recessive
what is the main symptom of fabrys disease
peripheral neuropathy
what enzyme is deficient in von gierkes
glucose 6 phosphatase
what enzyme is deficient in cori disease
alpha 1,6 glucosidase (glycogen debranching enzyme)
what enzyme is deficient in mcardles disease
glycogen phosphorylase
von gierkes is evident at what age
6-9m with spaced out feeding
what is the main symptom of cori disease
accumulation of branched glycogen (limit dextrans)
what are the main symptoms of mcardles
decreased plasma lactate
muscle aches and cramping
myoglobinuria after exercise
increased creatinine and aldolase
what are 2 examples of receptor mediated endocytosis
LDL
transferrin
where does transcription occur
where does translation occur
transcription- nucleus
translation- cytosol
a signal sequence directs proteins from __ to __
ribosomes
ER
where in the protein is the signal sequence found
N terminal
signal recognition particles move proteins from __ to __
cytosol to ER
what type of molecules are signal sequences
ribonucleoproteins
CFTR biosynthesis starts with it’s co-translational insertion into the membrane of what organelle
ER
efficacy of CFTR trafficking is controlled by what organelle
ER
where is the site of misfolded CFTR degradation
ER
how are misfolded CFTR proteins degraded
ubiquitination
where is the site of CFTR glycosylation
golgi
the CFTR is what type of channel
chloride ligand gated
what process regulates the CFTR channel
phosphorylation
when there is impaired chloride secretion in those with cystic fibrosis, this leads to what symptom
think mucous
how can you test for cystic fibrosis
sweat test
what chromosome is the CFTR gene found on
7
coated vesicles are important for what type of pathways
secretory
what type of vesicles are used for receptor mediated endocytosis
clathrin coated
what are 3 examples of receptors found in clathrin coated pits
LDL
growth factor
transferrin
COP I is used for __
COP II is used for __
I= retrograde (golgi to ER)
II= anterograde (ER to golgi)
what 4 processes occur in the mitochondria
beta oxidation
TCA cycle
ETC
ketogenesis
what 4 processes occur in the cytosol
fatty acid synthesis
glycolysis
pentose phosphate pathway
glycogenesis
what 3 processes take place in both the cytosol and mitochondria
heme synthesis
urea synthesis
gluconeogenesis
the urea cycle occurs in what part of the mitochondria
mitochondrial matrix
what 3 processes occur in the nucleus
DNA replication
transcription
ribosome assembly
where is the site of rRNA transcription and processing of ribosome assembly
nucleolus
what is the function of proteosomes
destroy misshaped and misfolded proteins
proteasomes have a role in what neurological diseases
parkinsons
what organelle contains oxidative enzymes such as catalase
peroxisomes
what are the 2 main functions of catalase
oxidize H2O2
metabolize ethanol
what fatty acids undergo alpha oxidation
long chain
very long chain
branched chain
what causes refsum disease
defect in peroxisomal alpha oxidation
what causes zellweger syndrome
defective peroxisome synthesis
what causes X linked adrenoleukodystrophy
mutation in the ATP binding cassette leading to defective transport of very long chain fatty acids into peroxisomes
what does type I collagen make up
bone
what does type II collagen make up
vitreous body
what does type III collagen make up
blood vessels
what does type IV collagen make up
basement membrane
what is the most abundant protein in the body
collagen
what amino acids make up collagen
proline, lysine, arginine
why is proline important in collagen
induces bond breaking
why is glycine important in collagen
it’s the smallest AA
what condition is associated with a decrease in type I collagen
osteogenesis imperfecta
what type of inheritance is osteogenesis imperfecta
autosomal dominant
what are the mutations seen in osteogenesis imperfecta
COL1A1
COL1A2
the genes defective in osteogenesis imperfecta, COL1A1 and COL1A2, encode for what
alpha chain for type I collagen
what form of osteogenesis imperfecta is the most severe
II
what are the 4 main symptoms of osteogenesis imperfecta
recurrent fractures
blue sclera
hearing loss
dentinogenesis imperfecta
osteogenesis imperfecta showing multiple organ involvement is an example of what
pleiotropy
what causes good pasture’s syndrome
anti-glomerular basement membrane antibodies (type IV collagen)
what condition results from a genetic defect in type IV collagen
alport syndrome
what 2 genetic conditions are X linked dominant
fragile X
alport syndrome
does collagen synthesis undergo posttranscriptional or posttranslational modification
post translational
where are the alpha chains of collagen synthesized
rough ER
pre-procollagen is present in what organelle
procollagen is present in what organelle
pre-procollagen- nucleus/ribosomes
procollagen- ER
prolines or lysines of collagen may undergo what type of posttranslational modification
hydroxylation
what cofactor is required for proline/lysine hydroxylation
vit C
deficiency in vitamin C may lead to __
scurvy
what component of collagen may be glycosylated
hydroxylysines
what is component of collagen is deficient as a result of vit C deficiency leading to scurvy
pro-alpha chain
what is the function of vitamin C with iron
reduce Fe3+ to an absorbable Fe2+ form
collagen propeptides have what structure
extra AA at N and C ends
disulfide bonds
what is the structure of procollagen
2 pro-alpha chains
how is procollagen secreted
exocytosis
propeptide removal and crosslinking of collagen occurs where
extracellular space
collagen fibrils are strengthened by what
lysine crosslinking
lysyl oxidase used in collagen crosslinking uses what as a cofactor
copper
in collagen synthesis
lysyl hydroxylase requires __ as a cofactor
lysyl oxidase requires __ as a cofactor
hydroxylase- vit C
oxidase- copper
what inheritance pattern is menkes disease
x linked recessive
what causes menkes disease
mutation of ATP7A
what is the result of ATP7A deficiency seen in mekes disease
impared copper absorption–>copper deficiency–> decreased lysyl oxidase–>no crosslinking
what are the symptoms of menkes disease
steely, kinky, minkey hair
osteoporosis/fracture
what are the copper lab results seen with menkes disease
low ceruloplasmin
low serum copper
what causes wilsons disease
mutation in ATP7B
what is the effect of ATP7B deficiency as seen in wilsons disease
impaired incorporation of copper into ceruloplasmin–> buildup of intracellular copper
what is the main symptom of wilsons disease
kayser fleischer rings (copper rings around eyes)
what is the urine lab finding for wilsons disease
high urine copper
low ceruloplasmin
high free copper
the hydroxylation of dopamine to norepinephrine by dopamine hydroxylase requires what as a cofactor
copper
vitamin C
what amino acid produces melanin
tyrosine
what amino acid produces serotonin
tryptophan
what amino acid produces melatonin
tryptophan
in classic ehler danlos syndrome, what collagen type is defective
V
in vascular ehler danlos syndrome, what collagen type is defective
III
a mutation in what enzyme can cause ehler danlos syndrome
lysyl hydroxylase
what are the main symptoms of ehler danlos syndrome
joint hypermobility
hyperextensible joints
where is the body is the main site of elastin
lungs
elastin is composed mainly of what type of amino acids
(polar or non polar)
nonpolar
what 3 amino acids make up elastin
glycine
lysine
proline
does collagen or elastin contain more hydroxyproline
less
elastin is made of what type of crosslinks
lysine (desmosine)
what is the function of alpha 1 anti-trypsin
inhibit neutrophil elastase to prevent alveolar wall degradation
what is the effect of alpha 1 antitrypsin deficiency
alveolar elastin degradation–>emphysema
almond breath is caused by __
cyanide poisoning
microdeletions are detected with __
FISH
what are 5 examples of microdeletion syndrome
williams
prader willi
digeorge
wilms
angelman
williams syndrome affects what chromosome
7
the deletion on chromosome 7 that leads to williams syndrome is a gene for what
elastin
what is the main symptom of williams syndrome
elfin faces
what are 2 examples of large segment mutation diseases
cru di chat
alpha thalasemmia
what 2 types of mutations can lead to beta thalasemmia
splice site
point mutation at promoter region
fibrillin is a major component of what
microfilaments
defective fibrillin leads to what autosomal dominant disorder
marfan
a mutation in what gene causes marfan syndrome
what does it code for
FBN1
fibrillin-1
what chromosome number is affected by marfan syndrome
15
what are the 4 main symptoms of marfan syndrome
tall
disproportionate long arms/legs
pectus excavatum
arachnodactyly
how does the lens subluxation differ between marfans and homocysteinuria
marfan= up and out
homocysteinuria= down
what receptor does cholera toxin bind to
GM1
where is the GM1 receptor that cholera toxin binds to located
intestinal epithelial cells
does cholera toxin perform anterograde or retrograde transport
retrograde
the dislocation of the A and B subunit of cholera toxin occurs where
ER
how does the A1 chain of cholera toxin induce disease
ADP ribosylation and activating adenylyl cyclase
another name for retrograde transport is ___
lipid based sorting pathway
cholera acts on G_
pertussis acts on G_
cholera= Gs
pertussis= Gi
do cholera and pertussis act reversibly or irreversibly
irreversibly
what ion channels are increased as a result of cholera toxin
sodium
chloride
what process is elongation factor a component of
transcription
pseudomonas and diptheria toxin interfere with ADP ribosylation by altering what
elongation factor 2
shiga and shiga like toxin stop what process
protein synthesis
what GLUT is an example of facilitated diffusion
GLUT5 for fructose
where is GLUT2 located
small intestine
liver
pancreas
where is GLUT4 located
skeletal muscle
adipose tissue
what receptor so skeletal muscle and adipose have that allows it to be under the effect of insulin
tyrosine kinase
where is GLUT5 located
small intestines
what is an example of secondary active transport
galactose and glucose SGLT
is the mitochondria inner or outer membrane permeable
outer
what is the function of the inner mitochondrial membrane
establish a protein gradient
what organelle contains its own circular genome
mitochondria
what is the main symptom of MERRF mitochondrial inherited disease
central vision blindness
what amino acid is essential for tumor cells
asparagine
erythropoietin is produced in the __
thrombopoietin is produced in the __
erythro- kidney
thrombo- liver
thrombopoietin and erythropoietin use what receptor
JAKSTAT
platelets lack __ but have __
lack nucleus
have mitochondria
platelets get most of their energy from metabolizing what energy source
glucose
how do platelets generate ATP
beta oxidation of fatty acids
the huntington gene is located on what chromsome
4
huntingtons occurs due to a mutation in __
fibroblast growth factor
the fibroblast growth factor mutation as seen in huntingtons is associated with what
achondroplasia
what causes scleroderma
fibroblast activation with excess collagen deposition
actin and microvilli make up what type of cytoskeleton structure
microfilaments
cilia and flagella make up what type of cytoskeleton structure
microtubules
microvilli are made up of what
actin
the z disc of muscle fibers contain what 2 proteins
vimentin
desmin
what is seen in rheumatoid arthritis
arginine residues in vimentin are converted to citrulline
antibodies to __ are specific for systemic lupus
dsDNA
microtubules are made up of what protein
tubulin
do microtubules contain ATP, ADP, GTP, or GDP
GTP
what 2 proteins are used for transport to the opposite end of the microtubule
dynein
kinesin
clostridium tetani toxin, herpes simplex virus, poliovirus, and rabies virus use __ for __ transport to neuronal cell bodies
dynein
retrograde
cilia are built from __ and __
microtubules
dynein
what is another name for primary ciliary dyskinesia
kartagener syndrome
what causes primary ciliary dyskinesia (kartagener syndrome)
dynein arm of microtubule defect –>immotile cilia
what causes hereditary spherocytosis
mutation in the RBC spectrin cytoskeletal protein
what is the effect of spectrin deficiency as seen in hereditary spherocytosis
RBC become spherical instead of concave
this causes anemia and splenomegaly
what 3 conditions cause hemolytic anemia
GDPD deficiency
sickle cell anemia
pyruvate kinase deficiency
burkitts lymphoma is caused by a reciprocal translocation of __
8, 14
mantle cell lymphoma is caused by a reciprocal translocation of __
11, 14
follicular lymphoma is caused by a reciprocal translocation of __
14, 18
what translocation and cancer causes Bcl-2 activation
14, 18
follicular
CML (philadelphia chromosome) is caused by a reciprocal translocation of __
9, 22
what translocation and cancer causes c-myl activation
8, 14
burkitts
what activates Ras
guanine exchange GDP->GTP
methotrexate and 5-flurouricil target what process
thymidine synthesis
etoposides and teniposide target what enzyme
topoisomerase II
what enzyme converts dUMP to TMP
thymidylate synthase
after how long of a fast does the brain begin to use ketone bodies
2-3 days
when ketone bodies are being used, is BUN high or low
low
ketone body production spares protein so no proteins are being broken down. this means BUM will be low
what enzyme does the liver lack that prevents it from using ketone bodies as a fuel source
SCOT (thiophorase)
what are the 4 major sources of phosphate
oxidative phosphorylation
phosphoglycerate kinase (glycolysis)
pyruvate kinase (glycolysis)
succinate thiokinase (TCA)
barbiturates (amytal) inhibit what complex of the ETC
I
rotenone (fish poison/insecticide) acts on what complex of the ETC
I
malonate inhibits what complex of the ETC
II
antimycin A and dimercaprol (BAL) inhibit what complex of the ETC
III
H2S, CO, and cyanide inhibit what complex of the ETC
IV
cyanide binds Fe__
CO binds Fe__
cyanide binds Fe3+
CO binds Fe2+
what is the presentation of cyanide poisoning
bitter almond smell
soot in nose/mouth
smoke
what is the main inhibitor of PFK1 of glycolysis
citrate
what activates acetyl CoA carboxylase of FA synthesis, while inhibiting PFK1 of glycolysis
citrate
what vitamin is the precursor for FMN and FAD
B2 (riboflavin)
FAD acts in what complex of the ETC
what enzyme does it act as an electron acceptor for
II
succinate dehydrogenase
what is the only enzyme of the TCA cycle that is embedded in the inner mitochondrial membrane
succinate dehydrogenase
