TBL12_ molecular cellular mechanism Flashcards
ECM, the plasma membrane, and protruding structures
A. The ECM is comprised of polysaccharide bound proteins and sphingolipids that keep cell hydrated and protected
B. Any protruding structures will connect cells together or serve special functions such as villi
C. Receptors, other proteins, and lipid rafts line the membrane
D. Below the ECM (if at the edge of the organ/tissue) is the basement layer
Endoplasmic reticulum
Rough ER- Ribosome “studded” on exterior
Functions:
1) Starts synthesis of exported proteins: Mucus
2) Proteins for other organelles: ie lysosome proteins
post translation modifications
Gene mRNA peptide
Smooth ER-
Ribosome in membrane..smooth and near plasma membrane
1) Stores G6P: sugar fate
2)Steroid hormone synthesis: estrogen
3) Detoxification: liver enzymes
4) plasma membrane maintenance
S(sugar) E(steroid synthesis) R
Golgi functions:
what proteins does glogi apparatus use?
Protein modification and sorting
Takes proteins from ER
* sorts proteins by destination
* Can add further chemical modifications
* O-glycan; start N-glycan
* Barcode
* Packages into vesicles for transport
* Membrane lipid maintenance
what are the different transport proteins?
COP II: ER to Golgi (Anterograde)
then Clathin later forms a viscle for export
COP I: resposible for retrograde transport Golgi to ER
How is exocytosis (anterograde) happening?
examples:
1) COPII + Clathrin initiate process at the eER
2) Two paths constitutive or regulated
Example:
Neuron neurotransmitter
Pancreas digestive enzymes
Endocytosis examples
immune cells (phagocytosis) –> response
Duodenum(transporter )—> lipid particle intake
mitochondria
– contain a small circular DNA
Functions:
1) ATP production- TCA, OxPhos, B-oxidation
2) cell fate: apoptosis
3) so many biochemical processes
lysosomes characteristics
Lysosome: cell digestion and recycling
-low pH to denature biomolecules
-has many hydrolase enzymes that function at low pH
-impermeable membrane
-made from Golgi apparatus sorting and break off
-can fuse with organelles or plasma membrane
membrane impermeable to enzymes has lysosomal specifiic proteins
lysosome functions
Functions:
1) Recycle biomolecules generating monomers or units
for export
2) AUTOPHAGY organelle recycling through fusion
3) Move lipids by between plasma membrane and
Golgi via fusion
4) Glucose-6-phosphate stored here
Peroxisome:
function
small body involved in oxidative digestion and from ER
Functions:
-contain oxidative enzymes
+ β-oxidation enzymes –very long chain fatty acids
+ α-oxidation enzymes – branched FATTY acid
+ oxidative synthesis of bile and cholesterol
+ have catalase to eliminate H2O2
glycolipids are made here( from ILS 3)
peroxisome associated diseases:
errors in formation of
peroxisomes with different severity due to PEX genes;
Zellweger spectrum disorders:
- zellweger syndrome: low peroxisome: cant make bile, steriods, cant digest ffatty acids
- Infant Refsum Disease:
accumulate very long chain fatty acids (faulty in B oxidation enzymes)
cranial abnormalities, seizures, vision/hearing loss
- zellweger syndrome:
low peroxisome: cant make bile, steriods, cant digest ffatty acids
Zell (lllllow peroxisome)
- Infant Refsum Disease:
accumulate very long chain fatty acids (faulty in B oxidation enzymes)
cranial abnormalities, seizures, vision/hearing loss
refSUM (sum of long fatty acids)
outter membrane of nuclus vs inner
outter memebrane is where the ER is bown to ribosime
inner is where chromain is
Large chromosome changes are seen in give percentages
- 0.5% of all live births
- 50% of first-trimester miscarriages
- 95% of tumor cells
Changes in length and gene locations can be detected
using _______
FISH technique
what are the steps in FISH
- denature our DNA and have probe ready
- hybridize together to bind probe
- analyze
what are the essential fatty acids to making many active lips
Linoleic acid (omega-6) ‘unhealthy’ and alpha-linolenic acid (omega-3) ‘healthy’ are essential fatty acids that make many active lipids essential in various systems.
Linoleic acid (omega-6) ‘
Omega-6 is “unhealthy” but essential and derived from animal
products.
alpha-linoleNic acid (omega-3)
Omega-3 is “healthy” and derived from fish and nuts.
what happens in the nervous system if lipids are not properly recycled?
where are they recycled?
Nervous
Brain gray and white matter contain high proportions of lipids. Without
proper lipid metabolism, especially recycling in the lysosome,
progressive dysfunction can occur. Importantly, visual pigments, and
signaling intermediates are lipids causing further nervous system stress
during lipid metabolic dysfunction.
what happens in the immune system if lipids are not properly recycled?
where are they recycled?
Active Lipids are integral to the immune system because they
determine INFLAMMATION STATE. Omega-6 anabolism leads (generally) to
is drives the immune system ON for pro-inflammation. Omega-3 has
the opposite effect (generally).
thats why they say animal meat is not as good for you!!!!
linoleic produces…..
arachidonic acid that makes 4 key
eicosanoids——> PET (L)
1) Endocannabinoids: an are G-inhibitory protein
signaling ligands that act mainly on CNS and PNS.
2) Thromboxanes: TXA2 is the opposite causing
vasocontraction and increases thrombosis
(coagulation). Thromboxane 2 = TXA2
3) Prostaglandins: PGI2 causes vasodilation and is
inhibits thrombosis (coagulation). Note PGI2 =
prostaglandin 2
4) Leukotriene and others will cover later
what are the 4
eicosanoids-
Protagladins (PGI2) vasodialtion inhibit thromboxin
Endocanabis , inhibits G inhibitory protein decrease cAMP
Thomboxanes (TXA2): vasoconstriction and increases thrombsis (coagulation)
Leukotriene
Sphingolipids
Sphingolipids are structural and active lipid molecules that all containing a
sphingosine backbone
Phosphatidylcholine are found in ______ and contain ____ and _____ in their polar head
plasmamembrane
Phosphate and choline
have glycerol base fatty acids
Sphingomyelin
Sphingomyelin is a major
component of myelin sheath in
nerve cells
have sphingosine base Fatty acids
how do we make sphingomyelin?
first you need palmitoyl-CaA and serine which will become ceramide (with sphingoside)
ceramide is where everything will branch from.
enzyme phospharylcholine will come in and add phophate and choline and diaglycerol will leave
final product: sphingomyelin
during catabolism sphigosine is going to leave the body
________is the first anabolic product and has an extra
fatty acid. It is therefore connected with lipid anabolism.
There is no R
ceramide
many products can be made from _____
ceramide
_____ has a polar head group at R (CHOLINE AND PHOSPHATE)
Sphingomyelin (sphingoPHOSpholipid)
A _______ is ceramide + a carbohydrate at R
cerebroside (MONOsaccharide-
sphingolipid)
A_________is ceramide plentiful in the CNS and has a complex (MANY) sugar attached at R
ganglioside (Polysaccharide-
sphingolipid)
how are gangliosides (sphigolipids with complex sugars) broken down?
they have a R =complex polysaccharide with NEGATIVE charged Sialic acid (Neu)
It is recycled by initial breakdown of the
carbohydrate units. A key enzyme is
b-hexosaminidase A: broken down between galactose and N-acetyl galactosamine
how are ganglionsides inmportant?
In ganglions (nerve cells junctions)
is a major lipid helping with signals and
insulation. It is also helps in a similar manner
within the CNS and eye
sugars in cerebrosides ( (Ceramide + 1 sugar)) and how are they broken down?
made from one galactose or one
glucose unit joined in β-glycosidic linkage to
ceramide. This is an unusual linkage that requires a
special enzyme.
glucocerebroside and need cofactor saporin
where are cerebrosides (glucosyl-ceramine) found?
Liver, speen and bone marrow
how is phingogomyelin broken down
present in membranes and nerves cells myelin
broken down by phingomyelinase which makes ceramide and a polar head group
when degraded, it is easily recycles and removed from the body by the spleen (immune cells) and liver .
where is sphingomyelin found?
eye, CNS, liver and spleen
what are lysosomal storage diseases?
- Absence of lysosomal enzyme
- Inability to breakdown complex molecules
- Accumulation → disease
- Most autosomal recessive
- Most of them have no treatment or cure
Lysosomes
- Membrane-bound organelles of cells
- Contain enzymes
- Breakdown numerous biological structures:
proteins, nucleic acids, carbohydrates and lipids.
Hexosaminidase and Tay-Sach’s
what is the problem? GM2 ganglioside (siliac acid) cant be recycled
GM2 ganglioside (siliac acid) cant be recycled due to b-hexosaminidase A is deficient (gene mutation of HEXA)]
GM2 ganglioside accumulates and cause the causes nearby NS cells to lose funtion
Tay-Sach’s clinical presentation
- Infants with this disorder typically appear normal until the age of 3 to 6 months, when their development slows, and
muscles used for movement weaken. Death is usually withing 2 years. - Caused by too much ganglioside buildup that leads to improper neuronal activity and cell death progressive
- Affected infants lose motor skills such as turning over, sitting, crawling and startle easily.
- As the disease progresses, children with Tay-Sachs disease experience seizures, vision and hearing loss, intellectual
disability, and paralysis. - An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this
disorder.
Gaucher’s disease
problem
- Epidemiology: Autosomal recessive disease with high
incidence in Eastern European Jewish population. Type 1 is
most common with symptoms starting (generally) early
childhood symptoms to adult on-set. - Glucocerebrosidase is defiecient, therefore accumulation of glucocerebroside
clinical presentation of gaucher
Thus effects on bone marrow is a key differential with either Pancytopenia (loss of red blood cells, white
blood cells, and platelets) or thrombocytopenia (low
platelets).
In addition effects on bone such as bone pain, osteoporosis, bone crises (femur), and pathological fractures
can be observed
Characteristic imaging are macrophages overloaded with
Glucocerebroside (Glucosyl-Ceramide) leading to a crumbled
paper appearance
Hepatosplenomegaly is seen
Niemann-Pick Disease
problem
NPD types A and B have prevalence is high in Eastern
European Jewish population with autosomal recessive
genetic features. It is caused by a mutation to acid
sphingomyelinase.
so accumulation of sphingomyelin is seen
Niemann-Pick Disease clinical presentation
NPD type A usually leads to an early death and
hepatosplenomegaly. It is common in the CNS and eye
leading to microcephaly (small head), a cherry red spot,
intellectual delay, and progressive neurodegeneration.
It has foam, lipid l
