Exam 1 Summary Flashcards
Describe the function of Golgi apparatus
Especially well developed in secretory cells
- plasma cells-antibodies
- pancreatic acinar cells- digestive enzymes
Transport between rER and Golgi
- Coatamer-coated vesicles
- COP-II: Anterograde
- COP-I: Retrograde
Vesicular trafficking
- Constitutive
- Regulated
- Lysosomal
Summarize exocytosis
- Regulated
- secretory
- stimulus-induced
- Ca2+ influx
- fusion of secretory vesicles - Constitutive
Summarize peroxisomes
- degrade ROS (hepatocytes)
- Converts water to oxygen and water
- fat metabolism
- peroxisomes proteins synthesized by free ribosome
What is Zellwegger syndrome?
Pathology: mutation in gene for peroxisome function or protein import
Affects: peroxisomes
Impact: dysfunctional peroxisome activity/ detoxification
Describe the lysosome
Targeting proteins for lysosomes
A) hydrolase precursors covalently modified by addition of mannose 6-phosphate (M6P)
B) Binding to M6P receptor C) Precursors transported to lysosome D) M6P receptor recycled -Protons pump help reduce pH
What is Tay-Sachs?
Pathology: mutation in HEXA gene for lysosome enzymes
Affects: lysosomes
Impact: death of neurons in brain and spinal cord
What is autophagy ?
- Double membrane vacuole
- essential role in starvation, cell differentiation, cell death and ageing
What are proteasomes?
- destroy proteins without involving lysosomes
- tagged with ubiquitin
Summarize lipids in the plasma membrane
-Amphipathic
-3 classes
A) Phospholipid
-most abundant
I. Phosphatidylcholine
II. Sphingomyelin
III. Phosphotidylserine
IV. Phosphatidylethanolamine
V. Phosphatidylinositol
B) Cholesterol- membranes inside the cell don’t contain cholesterol
C) glycolipids
Describe proteins of the plasma membrane
2 classes
A) integral
I. Transmembrane
a. Pumps/carriers/transporters
b. Channels
c. Receptors
d. Linkers
e. Enzymes
f. Structural proteins
II. Anchored
B) Peripheral
-Noncovalent association with integral membrane proteins
Summarize membrane biochemistry
- lipoprotein membrane allows transfer of non-polar lipids into blood
- fluidity is determined by fatty acids found in polar lipids
- shorter fatty acids and unsaturated fatty acids make membrane more fluid
- I.e. arachidonic acid and DHA
Describe the glycocalyx
Carbohydrate rich zones
A) glycolipids
B) glycoproteins
C) proteoglycans
- help establish micro environmental cell surface
- protection
- cell recognition
- cell-to-cell interactions(lectins)
What are lipid rafts?
- specialized cholesterol enriched micro domain
- signal transduction, virus infection and endocytosis
Summarize receptor-mediated endocytosis
- clathrin-dependent
- cargo-specific
-selective uptake Clathrin-coated pits A) Receptor recycled, ligand degraded B) Receptor and ligand recycled C) Receptor and ligand degraded D) Receptor and ligand trans-cytosis
Summarize vesicle targeting
I. Rab-GTPase interact with tethering protein
II. Docking complex
III. Accurate targeting via:
a. v-SNARE b. t-SNARE
What are the functions of an endosome?
-Endosomal processing
I. Early endosome
-sorts and r3cycles
II. Late endosome
- Receives protein for degradation - Receives new lysosomal enzymes - Matures to lysosome - Lysosome digestion
Summarize pinocytosis
- Clathrin-independent
- Non-specific
- Constitutive
- Fusion with lysosomes
Summarize phagocytosis
- Actin-dependent
- Cargo-specific
- Performed by macrophage/neutrophils
- Psuedopodia extension
- Fuse with lysosome
- Residual body of indigestible substances
Sumarrize the types of Actin
G actin- free actin
F actin- polymerized and ATP dependent
- polarized structure(+) (fast) and (-) (slow)
- bundle, network, single,
- cell function
- anchorage
- Core of microvilli and stereocilia
What is the type and function of the drug, phalloidin?
Type: Binds F-actin more tightly
Action: promotes excessive polymerization and inhibits de polymerization
What is the type and function of the drug Cytochalasins?
Type: blocks polymerization of actin
Action: inhibit cell movement, division, and induce programmed cell death
What is the function of Myosin ?
Myosin 2
Motor and skeletal contraction
- tail to tail interactions result in bipolar thick filaments
- each head binds
Stage 1: attachment
Stage 2: release
-ATP binding
Stage 3: Bending
-ATP hydrolysis
Stage 4: force generation
-Pi released followed by power stroke
Stage 5: reattachment
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What are the pathology and organelle affect by myoclonic epilepsy ragged red fibers?
Pathology: mutation in tRNA
Affected organelle: mitochondria
What is the pathology and organelle affected in Leber hereditary optic neuropathy?
Pathology: mutations in mitochondrial gene
Affected organelle: mitochondria
Summarize neutrophil migration
Extravasion
- Rolling
- Activation
- Adhesion
- Transemdothelial migration via diapedesis
- pass through basement membrane
What are the 6 classes of intermediate filaments?
1 & 2: keratin (epithelial)
3: vimentin & vimentin-like (meso-derived cells, muscle cells, glial & astrocytes)
4: neurofilaments (neurons)
5: lamins(nucleus): lamin A & B
6: beaded filaments: (eye-liens specific)
Describe intermediate filaments
- rope-like filaments
- non-polar and highly variable subunits
- functions
- structural
- stabilize cell structure
- maintain the position of nucleus and other organelles
- essential for integrity of cell-cell & cell-ECM junctions
What is the purpose of chemotaxis?
- seeks out inflammation
- N-formulated peptide attach to matrix
What is the pathology, affected organelle and impact of cystic fibrosis?
Pathology: mutation in gene coding for CFTR impairs proper transport of Cl- into and out of epithelial cells
Affected organelle: cystic fibrosis transmembrane conductance regular CFTR
Impact: salty tasting skin, poor growth, and poor weight gain despite normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath
What is the function of the inner membrane of the mitochondria?
3 major functions:
- oxidative reactions
- synthesize ATP
- regulate metabolite transport in and out of the matrix
What is the function of the matrix of the mitochondria?
- Oxidation of pyruvate and fatty acids
- Citric acid cycle
- matrix granule storage of Ca2+
What is the function of the outer membrane of the mitochondria?
-contains porins, Phospholipase, and Acetyl coenzyme A synthase
What is the function of the inter membrane space of the mitochondria?
Enzymes that use ATP
- creative kinase
- adenylate kinase
- cytochrome C
What are the 3 lipid classification?
- Simple lipids- triacylglycerol
- Derived lipids- fatty acids(saturated and unsaturated)
- Complex lipids-phospholipids and glycolipids
Describe the structure and function of cholesterol
Dietary lipids= troacylglecerol (TAG)
-27C atom
- amphipathic because of —OH
- present in membrane with—OH group towards the aqueous side
- both leaflets
- precursor to bile acid/bile salt synthesis
- precursor for Vit. D
State the structure, function of saturated fatty acids
- no. Double bond
- palmitic acid (18C) and stearic acid (18C) (most abundant in humans)
- saturated fatty acids bad for cardiovascular
Short(below 6 C) = mostly in milk
Medium= 6-10C
Long = 12-20 C (mostly in humans)
Give the structure, function of lipids in general
Dietary lipids= Triacylglycerol(TAG)
- 90%-95% of dietary lipids are TAGs
- provides 20%-30% of calories
- stored in adipose tissue
- structural components of: cell membrane, myelin
- cholesterol precursor to steroids and vit D
- prostaglandins (Eicosanoids) derived from fatty acids
- lipoprotein important for transfer of triacylglycerol and cholesterol esters
- ketone bodies derived from incomplete oxidation of the fatty acids in TAGs
Describe the structure of phospholipids
- base component is phosphatidic acid
- have non-lipid component
- all amphipathic
- presence of unsaturated fatty acid makes membrane susceptible to free radicals
Two types:
- phospholipids
- glycolipids
What are the 7 types of glycerophospholipids?
- Phosphatidylcholine(lecithin)- present on inner and outer leaflet
- Phosphatidylethanolamine
- Phosphatidylserine
4. Phosphatidylinositosol Derivatives include: -PIP2: Phosphatidylinositol biphosphate -IP3: inositol triphosphate -DAG: Diacylglycerol
- Cardiolipin
- most abundant in inner mitochondrial membrane - Plasmalogens and platelet activating factor( PAF)
- Dipalmitolphosphatidylcholine (dipalmitoyl lecithin) (DPPC)
- important component of surfactant
- high risk of RDS in premature neonates
- Lecithin-sphingomyelin ratio (L/S) measured to determine lung maturity- L/S> 2= mature
- L/S<1.5= immature
- Maternal steroid injections improve lung maturation
What are the types of glycolipids?
- Cerebroside = ceramide + monosaccharide
- Sulfatide= ceramide + monosaccharide+ sulfate
- Globoside= ceramide + oligosaccharide
- Ganglioside= ceramide+ oligosaccharide containing NANA
Summarize glycolipids basics glycosphingolipids
- ceramide+ carbohydrate
- found mainly on outer leaflet
- glycolipids + glycoprotein = glycocalyx
What are the categories of unsaturated fats?
Monounsaturated+ polyunsaturated
What are the essential polyunsaturated fats?
- Alpha linolenic acid (omega-3)
2. Linoleic acid (omega-6)
Where are trans fats found?
- margarine
- baked goods
- fried goods
What are the derivatives of alpha linolenic acid?what are their uses?
1st derivative- eicosapentaenoic acid(EPA) uses- anti-inflammatory, cardio protective
2nd derovative- decosahexaenoic acid (DHA)- neural brain development and vision
What are the derivatives of linoleic acid?what are their uses?
1st derivative- arachadonic acid uses: formation of eicosanojds
What are the types of eicosanoids and their uses?
- Prostaglandins
- PGE: mediators of inflammation
- thromboxane: platelet aggregation - Leukotrienes
- Mediator of allergic response that cause bronchoconstriction and itching
After what carbon in unsaturated fatty acids, can humans not add a bond?
After C 9
What does nutritional deficiency of fatty acids lead to?
Nutritional deficiency of essential fatty acids leads to scaly dermatitis, rough and dry skin, loss of hair
What are the high affinity Glucose transporters? What are the low affinity glucose transporters?
High affinity- glut 1, 3, 4
Low affinity- glut. 2 and 5
Where are GLUT 1 located?
Brain, RBC, kidneys
Where are GLUT 2 located?
Intestine, hepatocytes, renal tubules cells, B cell/pancreas,
Transports large amounts of glucose @high glucose concentration
- Intestines/mucosal cells: release of sugar
- Hepaatocytes: takes up glucose at high glucose levels
- Renal tubular cells: reuptake of glucose
- B-cells: transports large amounts and measures glucose levels
Where is GLUT 5 located? It’s function?
Intestines luminal side, seminal vesicles
- transports fructose (and glucose only when very high)
- release fructose —> glucose—> used for energy by sperm
Where are GLUT 3? What is the function?
Brain, neuron
-constant rate with normal and lower blood glucose concentrations
Where are GLUT 4 located? What is its function?
Fat cells, skeletal muscle, heart
- insulin dependent
- insulin mobilizes transport of GLUT-4 to membrane via endosome
- Insulin injection can lead to hypoglycemia due to rapid uptake
What are the major differences between GLUT and SGLT transporters?
GLUT- Na independent, facilitated diffusion
SGLT- Na-dependent, secondary active transport
Where are SGLT 1 used?
Intestinal mucosal cells
-symporters Na+ glucose/galactose against gradient
Where are SGLT 2. used?
Kidney
-symporter Na+ + glucose
What causes microencephaly?
Pathology: GLUT-1 deficiency
Affected organelle: GLUT-1 transporter
Impact:
- epilepsy like seizures
- ataxia
- delayed psychomotor response
- movement disorder
- impaired speech
What is the rate of diffusion determined by in carrier mediated diffusion?
- Saturation
- Number of transporters
- Conformational change
- Gradient
What does the flux depend on in simple diffusion?
- 🔼C
- Electrical gradient
- Temperature
- Surface area of membrane
- Molecule mass
- Membrane permeability
- Can be positive or negative
Net flux=0
Fick’s law= flux
How are hydrogen bonds broken in amino acids?
Heat, 5-10M urea, salt
How are ionic bonds broken in amino acids?
Strong acids and bases
How are hydrophobic interactions in amino acids?
1-2% detergent
How are disulfide bonds broken in amino acids ?
B-mercaptoethanol
2-mercaptoethanol
What are the liver function tests?
- ammonium
- albumin
- bilirubin
What are the indicators of decreased cellular integrity(for the liver)?
- ALT and AST used by not very specific
- Even though hepatocyte is damaged it can still function
- High ALT levels indicate liver damage (AST/ALT<2)
What is the cause of bile duct obstruction ?
Obstructed by gallstones or tumors
What are the indicators of bile duct obstruction?
- ALP-1
- GGT
- Conjugated bilirubin
- Increase in both ALP-1 and GGT can indicate bile duct issue (but not either alone)
What are the causes of pancreatitis?
- Acute: heavy alcohol intake , gallstones
- Chronic: CF, hypertriacylglycerolemia, ethanol abuse
What are the indicators of pancreatitis?
- Serum amylase (a-amylase)
- Lipase (pancreatic lipase)
What are the alcohol abuse and Cirrhosis indicators?
- AST/ALT >2 indicates cirrhosis or alcohol abuse
- High ALP levels can be due to cirrhosis due to fibrosis of intrahepatic bile ducts
- Lipase /Amylase >2 indicates damage due to alcohol
What is alanine aminotransferase (ALT)?
Enzyme needed for gluconeogenesis and urea cycle
-ALT higher concentration in hepatocytes
Where is Aspartate aminotransferase found?
High concentration in liver, heart
What is the Alkaline phosphates (ALP)?
Creates alkaline pH of bile
-hepatic bile canaculi cells and biliary duct cells have high concentration ALP
What are the two types of ALP?
- ALP 1: Indicator of bile duct obstruction
- ALP 2: indicator of bone disease (Padgett disease or bone tumor ) or found at high levels in growing children and pregnant women
What is y-glutamyl transferase (transpeptidase) (GGT) ? What does it do?
-transports AA into cell
- uses glutathione (GSH)
- glutathione has peptide bond located at y carbon and not a carbon
-can increase due to enzyme induction by ethanol
What is creative kinase and how is it formed?
- catalyzes reversible reaction
- At high ATP levels, creative phosphate (CrP) is formed
- At low ATP levels, ATP formed from CrP
Where is creative kinase found?
CK found in cytosol and mitichondria
-Isozymes of CK
- CK-BB(CK1) - found mostly in brain and intestines
- CK-MB(CK2)- found in heart (30%) and skeletal muscle (2%)
- CK-MM(CK3)- found in heart (70%) and (98%)
- elevated CK-MM indicative of rhabdomyolysis or muscular dystrophy
What is troponin?
Not an enzyme
-two types: cTnl and cTnT
What are the disease indicators of myocardial infarction?
- CK-MB >3% indicates that MI has occurred
- CK-MB/total CK indicates severity of MI
- LDH can be used if CK, CK-MB and cTnl/cTnT not available or many days have passed (half life of 5 days)
- “flipped” LDH-1/LDH-2 ratio (LDH-1>LDH-2)
If cellular injury leads to increased levels of specific enzymes in serum, how much would be mild, moderate, and marked?
Mild: 2-3 times
Moderate: 3-20 times
Marked: >20 times
What are the cons of stem cell tech?
- ESCs genetically different from patient
- Transplant may induce immune response
How is cloning done with stem cell tech?
Create cloned embryo with donor nucleus
What are the cons of using stem cells for cloning?
- inefficient
- deleterious effects and die early
- premature aging
- abnormal embryonic development
How can stem cell cloning be used for therapeutic reasons?
- generate organ
- correct genetic error
What are the cons for cloning for therapeutic reasons?
- inefficient
- large number of eggs needed
- excessive hormone therapy
- surgery to retrieve eggs
