Week 1 Flashcards
Five different properties of malignant cancer cells
1) Unresponsive to normal signals for proliferation control
2) De-differentiated (lack specialized structures/functions)
3) Invasive (outgrowth into normal neighbors)
4) Metastatic (shed and proliferate)
5) Clonal in origin (derived from single cell)
Cancer is the accumulation of ____________ over time. Cancer ________ can be inherited in a ______ or _______ pattern
many somatic genetic alterations and mutations
Susceptibility
Dominant or recessive
4 steps for carcinogenesis
1) Tumor initiation
2) Tumor promotion
3) Tumor conversion
4) Tumor progression
Carcinogenic mutations can occur in two types of genes, ________ and ______
Oncogenes
anti-oncogenes (Tumor Suppressors)
Oncogenes
Genes that normally stimulate cellular proliferation - are activated in carcinogenesis
= Gas Pedal
Tumor Suppressors (anti-oncogenes)
normally inhibit cellular proliferation - inactivated in carcinogenesis
= Brakes
Types of cytogenetic abnormalities associated with malignancy: (3)
1) Translocations and gene deletions
2) Loss of heterozygosity
3) aneuploidy
Events that can produce loss of heterozygosity (2)
1) Mitotic recombination
2) Loss of chromosome or translocation
The Retinoblastoma Gene is on chromosome ______ and acts as a ___________
chr13q14
tumor suppressor
Patients with “inherited” RB are ________ for the RB gene in their normal tissues and ________ for the RB gene in their tumor cells. Patients with inherited RB therefore typically have ________ retinoblastomas
heterozygous
homozygous
bilateral
Patients with no family history of RB must have ________ in order to get a retinoblastoma. Patients in this case thus typically have ______ retinoblastomas.
- two independent events occurring in retinal cells that cause both copies of RB gene to be non-functional.
- unilateral RBs
RB is hyperphosphorylated in _________ cells at ________ stage of the cell cycle
rapidly proliferating
at S or G2 of the cell cycle
__________ phosphorylates RB protein and causing it to be _________. _______ levels fluctuate while ______ levels are always the same.
CDKs + Cyc complexes
-inactivated
Cyc level fluctuates, CDK level always the same
When RB is phosphorylated in no longer is able to _______________
inhibit transition into S phase, allowing cell division cycle to begin
RB is hypophosphorylated in _________ cells at _______ stage of the cell cycle. When RB is not phosphorylated it _____________
non-proliferating cells
at G0 or G1 of the cell cycle
inhibits entry into S phase
RB is a target for many ______________. These drive a quiescent cell into S phase by producing __________
animal tumor viruses
viral proteins
_________ and ________ are examples of animal tumor viruses.
SV40 and HPV
HPV virus infects cells causing them to produce ________ and _______ proteins which inhibit _______ and ________ respectively
HPV E7 and E6 proteins
RB and p53 tumor suppressors
______, ________ and _______ are homologs that act as tumor suppressors. Their activity is _________.
RB, p107, p130
tissue specific
The APC gene is a ________ and when mutated, is involved in _________. APC gene is located on chromosome _____
Tumor suppressor gene
Familial Adenomatous Polyposis (FAP)
chr5q
Familial Adenomatous Polyposis is inherited in a _________ pattern, and requires loss of hederozygosity in adenomatous polyps of the colon to cause _____________
autosomal dominant
colon cancer by age 50
APC gene encodes a protein that regulates localization of ____________.
Beta-Catenin protein
B-Catenin protein is typically bound to _________ and kept sequestered in the _________. When B-Catenin is free in the cytoplasm, the _______ acts to break it down. Without this, B-catenin will _________
E-Cadherin, kept sequestered in plasma membrane
APC protein
enter the nucleus and activate transcription of oncogenes (c-myc)
BRCA1 and BRCA2 to function in ________.
DNA repair
Inherited BRCA1/2 cases result from __________. Acquired cases of _______ mutations in these genes have NOT been found in tumors (different from RB gene)
LOH –> mutant/non-functional BRCA1/2
Somatic mutations
If you are heterozygous for BRCA2 mutations = ___________
If you are homozygous BRCA2 mutations = ___________
This means that BRCA2 is ________ with __________
Heterozygous –> breast cancer due to LOH in mammary gland cells
Homozygous –> Fanconi’s anemia
BRCA2 is allelic with Fanconi’s anemia D1 gene FANCD1
p53 is a ________ gene that acts as ___________ by preventing ___________
tumor suppressor
“Guardian of the genome”
potentially deleterious mutation
Cellular functions of p53 (4)
1) Transcription Factor
2) Required for apoptosis
3) Mutation “hotspots”
4) Interfered with lifecycle of many human viruses
P53 acts as a transcription factor, and is important for ____________
preventing cells from replicating damaged or foreign DNA
p53 is required for apoptosis by __________
preventing cells with DNA damage beyond repair from replicating
Why was p53 originally thought to be an oncogene instead of a tumor suppressor?
“Dominant Negative” p53 mutations - heterozygous p53 mutation can produce mutant protein that binds the wild-type p53 protein and inactivates it
Oncogenes were first discovered in ________. Normal cells are ________ while cancer cells are ________
oncogenetic retroviruses (RNA viruses that infect cell and take over its replication machinery)
anchor dependent
NOT
Viral ongogne (V-onc) proteins allow viruses to _________
rapidly transform appropriate infected cells to malignant phenotype
pp60v-src is a ________ and ________ that acts to _____________
viral oncogene protein and membrane bound kinase
phosphorylate tyrosine residues of proteins causing changes in gene expression
v-erb-B is a ________ that codes for a protein similar in structure to _________, and acts as a tyorsine specific protein kinase that __________
viral oncogene protien
EGFR (epithelial growth factor cell surface receptor)
stimulates growth
v-abl is a ________ that acts as a protein kinase. v-abl is similar to ________
viral oncogene protein
human c-ABL gene (the one found in BCR-ABL translocation in CML) - Philadelphia Chromosome
Endogenous oncogenes are called _______. They are part of normal functioning human cells and must undergo _________ in order to become carcinogenic. Therapy therefore can only target _________
c-onc
mutation
c-onc over-expression (not all c-onc genes)
Oncogenes and tumor suppressor genes are being used as ________ in ________ and _______
“molecular markers”
cancer diagnosis and prognosis
“Heat Map” in personalized medicine
used to correlate many types of molecular data aka bioinformatics (gene copy number, gene expression, heat maps, mutations, etc.) with relevant clinical information (tumor grade, survival, age, tumor stage, etc.)
Breast cancer Xpress Chip
personalized medicine
info used for diagnosis, prognosis and therapy
-Measures expression of 123 genes known to be altered in breast cancers
-high erbB2 –> treat with Herceptin
High ER levels –> treat with tamoxifen
Criteria for classifying Li-Fraumeni Syndrome (3)
must have all 3
1) Proband with a sarcoma diagnosed before age 45
2) First degree relative with cancer under 45
3) A first or second-degree relative with any cancer under 45 years of age or a sarcoma at any age
Knudson Two Hit Hypothesis: Li-Fraumeni Syndrome
Hit 1 = premalignant
Hit 2 = Carcinoma
Multi-locus model - hits can be on two different genes (unlike RB)
Hit 1 LFS con occur via…(4)
1) Point mutation –> oncogene activation (RAS, myc) or tumor suppressor inactivation (p53, RB)
2) Amplifications/deletions
3) Epigenetic silencing by methylation
4) Insertion of retrovirus containing oncogenes
Hit 2 LFS
Amplification of HER2 oncogene
P53 response to UV exposure
1) p53 bound by mdm2
2) DNA damage, cell abnormalities or hypoxia –> p53 activated
3) Cell cycle arrest (DNA repair, cell cycle restart) or apoptosis/elimination of damaged cells
Von Hippel-Lindau clinical manifestions
Formation of cystic and highly vascularized tumors in many organs
- Cerebellar/Spinal cord hemangioblastomas (Major cause of death in VHL patients)
- Clear Cell Renal Cell Carcinoma (Major cause of death in VHL patients)
- Retinal Hemangioblastomas
-Must have 2 criteria: one VHL lesion + family history, or two VHL lesions
VHL inheritance is _______ with high _______ and ________
AD
penetrance and variability (severity/onset)
VHL is caused by a mutation in a ___________ gene located on __________. This gene codes a protein that is part of a complex that _____________ and ________. It is _______ dependent.
tumor suppressor
chr3p25-26
targets unwanted proteins for proteosomal degradation by ubiquination and Hypoxia Inducing Factor (HIF)
oxygen dependent
Under normal oxygen, HIF is __________. If VHL ubiquinates HIF, then ________
hydroxylated by proline and asparagine hydroxylase
proteosomal degredation
Under hypoxic conditions, HIF is ____________. HIF thus _______ and activates ________________.
not hydroxylated and not degraded
accumulates
activates transcription of genes involved in angiogenesis, metabolism, apoptosis, low O2 survival, and other cancer growth promotion processes
Cells with a mutated or lost VHL gene behave like ___________. This results in ______________
they are constantly hypoxic
HIF accumulation, aneuploidy, disruption of primary cilia maintenance → renal cysts and renal cell carcinoma formation
The VHL gene 4 actions:
1) Regulate HIF
2) Suppress anuploidy
3) Maintains primary cilia
4) Stabilizes microtubules
Clear Cell Renal Cell Carcinoma (ccRCC) follows the ________ theory because two copies of _________ are required
Two-hit
inactive VHL gene
The lipid bilayer is a ______ and _______ structure. The lipid molecules are constantly _______ - catalyzed by ________
dynamic and fluid
changing places with its neighbors in the bilayer
Flippase (ATP driven)
Membrane fluidity depends on ______ and ______. _______ decreases fluidity.
Composition and temperature
cholesterol
Phospholipid is a _______ molecule synthesized in the ________. It does not __________.
amphipathic
ER
spontaneously flip/flop
Most common Phospholipids include _________, ________, and ___________, and are all derived from __________
Phosphatidylethanolamine (PE)
Phosphatidylserine (PS)
Phosphatidylinositol (PI)
glycerol
Sphingolipid is a _______ molecule synthesized in the ________. _______ is an example, derived from ____________
amphipathic
ER
Sphingomyelin
Sphingosine
Cholesterol is a _______ molecule synthesized in the _______. It is made up of a ________, _________ and ________.
Amphipathic
ER
Polar hydroxyl group
Hydrocarbon tail
Rigid steroid ring (intercalates with hydrophobic tails)
Cholesterol is important in ________ and ______, therefore its abundance is carefully regulated.
Determining membrane fluidity and membrane thickness
less cholesterol = more fluid and thinner
The cell membrane is ________, which is established during __________.
Assymetrical, established in ER during synthesis
Negatively charged molecules (PS, PE, PI) are more abundant on _________, while PC, sphingomyelin, and glycolipids are more abundant on _______. _________ is equally distributed.
internal surface
external surface
Cholesterol
HMGCoA Reductase is the _________ in cholesterol synthesis and is a target for __________
first/rate limiting step
Statins (treat high cholesterol)
Sterol Regulatory Element Binding Protein (SREBP)
Transmembrane protein
- Binds transcription factor keeping it inactive
- when cholesterol is low –> TF cleaved from SREBP in golgi by proteases
Cholesterol Transcription Factor
- Basic helix-loop-helix DNA binding protein
- Bound by SREBP (inactive)
- Cleaved from SREBP in golgi when cholesterol is low (activated)
- Translocates to nucleus –> express genes to produce more LDLR and increases all enxymes involved in cellular synthesis of cholesterol
Cholesterol levels are detected by ___________
sensors in ER membrane (where cholesterol is lowest in the cell)
SCAP (SREBP Cleavage Activating Protein)
- Binds to SREBP and sterols (cholesterol)
- Cholesterol sensor
- Involved in cleaving TF off SREBP (recognizes, but doesn’t actually do the cleaving)
- Escorts SREBP to golgi via vesicular transport when cholesterol is low
Insig
SCAP binding protein
- Binds SCAP only when cholesterol is HIGH
- blocks signaling part of SCAP that typically binds COPII (vesicle transport protein)
-When cholesterol is low: insig no longer binds SCAP and ACAP/SREBP goes to golgi in vesicles
RIP (Regulated Intramembrane Proteolysis)
Cleaves TF from SREBP in a 2 step proteolysis (S1P / S2P)
-can sometimes cut in transmembrane domain
-Critical for notch signaling and development
________ acts to bring cholesterol into the cell
LDLR
Plasma volume is _____ L and consists of __________
3 liters
whole blood without the cells
Extracellular Fluid (ECF) volume is _______ L plus another ____ L for the “Third Space”. This consists of ______, _______, and _______
13 liters
5 liters
Plasma, Lymph, and interstitial fluid
Intracellular Fluid (ICF) volume is _____ L and consists of __________. It has a slight _____ charge
27 liters
mitochondrial, vesicular, nuclear, ER, and other sub-compartments
Negative
Na+ concentration
functionally impermeable
High concentration outside cell, low inside cell
K+ concentration
membrane permeable
Low concentration outside cell, high inside cell
Cl- Concentration
membrane permeable
High concentration outside cell, low inside cell
Protein concentration
membrane impermeable
Low concentration outside cell, high inside cell
H2O concentration
membrane permeable
Same concentration inside and out
Functional properties of membranes (2)
1) Impermeable to charge (lipids create/maintain electrical potential)
2) Selectively permeable (allows some charged/polar molecules cross - mediated by channels/transporter proteins inserted in membrane)
Routes to traverse a membrane (2)
1) Channels
2) Transporter
Membrane Channels are ____________. They have 2 properties:
passive pores/tunnels in the membrane
1) Selective for particular ions
2) Molecular gates (substance can pass only when gate is open)
Membrane Transporters
substances cross membranes by binding to proteins and being escorted (“carried”) across
- Work much slower than channels
- Primary and secondary active transporters
3 mechanisms cells have evolved to prevent from swelling and bursting:
1) Water impermeable membrane (not common, most are highly permeable to water)
2) Cell Wall - keep cell from swelling by brute force (hydrostatic force counters osmotic force)
3) Osmotic Balance in and out- Dilute water with solute outside of cell so it matches inside
In order to generate osmotic balance you must have ________ and _______, but _______ does not matter
equal osmolarity inside and out and solutes must be non-permeating
Chemistry doesn’t matter (solutes in/out can be different)
Diffusion
Random, thermally-agitated movement of molecules
Osmosis
Diffusion of water
-Net inward movement of water across a semi-permeable membrane
- Membrane permeable to solvent but NOT solute –> solute sucks water into cell
- Faster than simple diffusion
_______ is the only thing that can change the volume of a cell and this happens based on ____________
WATER movement
concentration of non-permeating solute
Osmolarity (osM)
Total concentration of solute particles
EX) 1M NaCl = 2 osM NaCl
Equivalents (mEq)
-number of combining weights per liter
First convert each ion to mosM
Second multiply by valence of the ion in question
Tonicity:
Hypertonic –>
Hypotonic –>
Isotonic –>
Hypertonic –> makes cell shrink
Hypotonic –> makes cell swell
Isotonic –> no net change in volume
Reflection coefficient (sigma)
How well a membrane reflects a substance
Between 0 and 1
0 = as permeable as water
1 = not permeable at all
How does treating Diabetic Keto Acidosis cause cerebral edema?
-High [glucose] in ECF because no insulin present for uptake into cells
• Treat in clinic by injecting insulin
- BUT if plasma osmolarity falls too quickly, glucose in brain will create osmotic gradient across brain capillaries
- Blood brain barrier is relatively impermeable
→ water sucked out of brain capillaries → cerebral edema
VAMP (vesicle association membrane protein) contains a ______ and _______ domain. It acts to __________
VAMP is on vesicle membranes
- Trans-membrane domain + H domain
- Fuses with SNAP-25 and Syntaxin present on cell membrane in zippering mechanism (H-domains)
SNAP-25 has _______ domains and a ___________. It is located in __________
- 2 SNARE domains + modified loop that buries in outer leaflet of membrane
- In cell membrane
Syntaxin has a _______ and ______ domain and is located in ____________
-Transmembrane domain (anchors into cells’ plasma membrane) + H domain
H domain (aka SNARE domain)
- amphipathic alpha helix
- Hydrophobic region and charged residue → can come together to form cold coil motifs
- Four parallel a-helixes come together
- Allows repulsive forces caused by hydration dipoles to be overcome
SNARE proteins involved in membrane fusion include _____, _______, _______. All contain H-domains, but only _______ and ________ contain transmembrane domains. These proteins all work to ______________
VAMP, SNAP-25, Syntaxin
VAMP
Syntaxin
Bring vesicle membrane and cell membrane into close proximity, allowing spontaneous fusion of membranes
NSF
- Regulates SNARE-based fusion
- breaks very stable zipper formation of SNARE complex
- ATPase, hexomer (6 together), barrel structure each with an ATP
- Hydrolyzes ATP to unwind SNARE complex that goes into hole of barrel
- Unwinding causes Syntaxin to be denatured
alpha-SNAP
aids NSF by recruiting it to the zippered complex for unwinding
N-sec 1
- Acts in regulation of SNARE-based fusion
- Activator: Folds Syntaxin 1 in active conformation, priming it for fusion
- Inhibitor: fusion not allowed while N-sec1 is still bound
- -> Must remove n-sec1 to allow VAMP to fuse
- -> Trigger mechanism, regulated by calcium
The many different SNAP, VAMP, and Syntaxins in our genome allows for ___________
regulation!
Only certain combinations of VAMP, SNAP, Syntaxin can fuse together –> specificity
Gp41 protein (HIV)
- sits on envelope outside capsid
- Transmembrane + 2 H domains (amphipathic a-helixes) + Fusogenic peptide domain (Highly hydrophobic AA, buries into lipid bilayer)
-2H domains form cold coil with 2 a-helixes, in anti-parallel formation
- Brings transmembrane domain and fusogenic peptide domain close together
- Allows fp to imbed into membrane an facilitate membrane fusion
Viral fusion is regulated at the level of ___________. This means that the virus must undergo a ____________
activation
conformational change: stable –> metastable conformation
Bulky solutions are always _______.
electrically neutral
If Vm = E (equilibrium potential) then…
the internal charge is sufficient to keep ion from diffusing out of cell, at equilibrium
If Vm does not equal E then there are 2 possibilities:
1) membrane is impermeable to ion
2) Membrane is permeable to ion and therefore ion must be pumped across the membrane because it is not distributed at equilibrium
Principle of electrical neutrality states that…
[anions]in = [cations]in and [anions]out = [cations]out
Osmotic balance states that…
number of particles in = number of particles out
Donnan rule states…
[K+]o [Cl-]o = [K+]i [Cl-]i
The Na/K pump pushes ____ out of cell and _______ into cell. It uses _____. The pump is also _______ and _______
3 Na+ out
2 K+ in
ATP
Saturatable and electrogenic (makes Vm more negative)
The primary short term determinant of membrane potential is NOT the Na/K pump, but _____________
Relative membrane permeabilities to the different ions
Steady state is different from equilibrium because in steady state…
[Na+] and [K+] don’t change over time, but we need a constant energy input → we are NOT at equilibrium
Relative permeability of K+ and Na+
the number of K+ vs. Na+ channels in a certain cell determines if membrane potential is closer to Ek or Ena
Driving force
the difference between membrane potential (Vm) and equilibrium potential (Eion)
More channels –> more current –> more driving force –> more current
Neurons and other excitable cells are much more sensitive to _____ rather than ______ because _________
[K+] out, [Na+] out
because its starting concentration outside the cell is much smaller than Na+, and thus is much more sensitive to small changes in concentration
Law of Mass Action
For any reaction A+ B ←→ (kf and kr) C + D
Forward rate, vf = kf [A][B] and reverse rate, vr = kr [C][D]
Equilibrium constant, Keq = kf/kr = [C][D] / [A][B]
pKa = ?
lower pKa means…
higher pKa means…
Range of pKas we deal with biologically is ___ - ____
-log (Ka) = -log ( [H+][A-] / [HA] )
lower pKa = stronger acid, stronger propensity to give proton
higher pKa = stronger base, stronger propensity to accept proton
Range of pKas we deal with biologically is 3-7
Henderson-Hasselbach equation for weak acid/base
HA ←→ H+ + A-
pH = pKa + log ([A-]/[HA])
proton acceptor / proton donor
When acid or base is 50% deprotonated and 50% protonated, then pH = pKa
H-H for bicarbonate buffer system:
pH = 6.1 + log [HCO3-]mM / .03PCO2 mmHg
Metabolic acidosis = ?
Respiratory acidosis = ?
Metabolic alkalosis = ?
Respiratory alkalosis = ?
Metabolic acidosis – bicarb (HCO3-) too low
Respiratory acidosis – pCO2 too high
Metabolic alkalosis – bicarb too high
Respiratory alkalosis – pCO2 too low, due to poor lung function
Normal ranges of:
pH =
[HCO3-] =
pCO2 =
pH = Arterial 7.34 - 7.44, Venous 7.28-7.42
[HCO3-] = 24mM pCO2 = 40 mmHg
Effective buffering range:
[A-]/[HA] = 0.1 to 10
Within one pH unit on either side of the pKa
There are _______ (#) of Americans with Crohns, with a peak onset at _______ years of age
1.4 million
15-30 years
Smoking increases risk for _________, while former smokers/nonsmokers increase risk for __________
Crohns
Ulcerative Colitis
Crohn’s vs. Ulcerative Colitis
Hematochesia (bloody stool/diarrhea)?
Crohn’s: Rarely
UC: Commonly
Crohn’s vs. Ulcerative Colitis
Location?
-Crohn’s: Ileum, upper GI tract, may affect entire GI tract
(Rectal involvement is uncommon)
-UC: Rectum, NOT in upper GI tract
Crohn’s vs. Ulcerative Colitis
Pattern?
- Crohn’s: Discontinuous (skip lesions)
- UC: continuous
Crohn’s vs. Ulcerative Colitis
**Fistulas?
- Crohn’s: Perianal disease is common
- UC: Perianal disease is rare
Crohn’s vs. Ulcerative Colitis
Inflammation?
- Crohn’s: Transmural
- UC: Mucosal
Extraintestinal manifestations are present in ____% of IBD patients, and can include…
25%
- Erythema nodosum, Arthritis, Pyoderma gangrenosum, tendinitis
- Pancreatitis, pleuritis, myocarditis, sensorineural hearing lossm iritis, uvitis, etc. (See slide)
Inflammatory Bowel Disease
inappropriate inflammatory response to intestinal microbes in a genetically susceptible host
Rising prevalence of IBD is thought to be because of… (4)
- Changes in diet
- Antibiotic use
- Altered intestinal colonization (eradication of certain parasites)
- Tobacco
DKA patients present with…
-Rapid, deep breathing (Kussmaul respirations), nausea, vomiting
- Thirsty, frequent urine output
- Polyuria (urinating a lot)
- Polydipsia (drinking a lot)
-Very thin (weight loss)
Some exam findings:
-Fruity odor to breath, increased cap refill time, cool hands and feet, diffuse abdominal tenderness
Major metabolic disturbances in in DKA include:
1) Elevated blood sugar
2) K+ Derrangements (Ketonemia/Ketonuria)
3) Metabolid Acidosis
4) Dehydration
Hyperglycemia is when glucose is >______(#) occurs in DKA because…
> 200mg/dL
-No insulin → can’t take up glucose, body keeps churning more glucose out
K+ Derrangements occur in DKA because…
Body tries to save water by increasing Na+ at the expense of K+
→ H+ pushed into cell and K+ pushed out of cells
-Need to give patients lots of K+, but CAREFULLY
Metabolic Acidosis occurs in DKA when pH is
ph
Dehydration occurs in DKA because…
-Excess glucose in filtrate, cannot be reabsorbed, pulls lots of water into urine
→ Weight loss, dehydration, electrolyte imbalances, large volumes of urine
_______ sense glucose and releasesinsulin
Beta cells of the pancreas
Type 1 diabetes
autoimmune destruction of B-cells, results in insulin deficiency
Insulin Release in Beta Cells:
1) Glucose enters cell through __________ → glycolysis → increase in ______________
2) → Closes __________, no ______ leaks out → __________ of membrane
3) → opens __________ → _____ influx
4) → Exocytosis of _______________
1) GLUT2 transporter
intracellular ATP to ADP ratio
2) ATP-sensitive potassium channel, K+
depolarization
3) voltage-gated calcium channel, Ca2+
4) insulin containing secretory granules
3 Targets of insulin
1) Liver
2) Muscle
3) Adipose
Insulin acts to _______. If you are insulin deficient, then…
STORE ENERGY (glycogen, protein, fat)
- Glucose cannot be taken into cells despite adequate supply → hyperglycemia
- Body must use another energy source: lipolysis, fatty acid oxidation (liver), ketoacids
In the liver insulin…
+ glucose uptake, glycogen synthesis
- glucogenesis
- ketogenesis
+ lipogenesis
In muscles, insulin…
+ glucose uptake, glycogen synthesis
+ protein synthesis
In Adipose, insulin…
+ glucose uptake
+ triglyceride uptake
+ lipid synthesis
Risk factors for Cerebral Edema when treating DKA
- Sicker or younger = higher risk
- Too many IV fluids, or too much insulin (quick osmolality changes)
Signs of Cerebral Edema (3)
hypertension, bradycardia, fixed/dilated pupils (late sign)
Primary Active Transport
3 Examples
Derive energy directly from splitting of ATP
EX) Na/K pump
EX) Intracellular H+ pump
EX) Intracellular Ca2+ pump
Intracellular H+ pump, pumps ________ into intracellular membrane bound oranelles
H+
Intracellular Ca2+ pump, pumps Ca2+ into _________ and out of the __________
into membrane bound compartments, and out of the cytoplasm
Secondary Active Transport
- most common pump
- Energy used to do direct work of pumping does NOT come from metabolism (ATP), comes from a secondary source
- Usually the downhill “leak” of Na+ into the cell
- ultimately relies on Na/K pump
Cotransport
Secondary active transporter
Move different solute species in the same direction
Electrogenic
one cycle produces a net charge transfer across the membrane
Na+/AA pump
cotransporter, electrogenic
Na+ leak in used to pump AA IN to cell
Na/K/Cl pump
cotransporter
Inward leak of Na+ used to pump Cl IN to cell
Exchange transport
secondary active transporter
Move solute in opposite directions
Na+/H+ pump
Exchange transport
- Na+ leak in, pump H+ out
- Any cell with a membrane potential
Na+/Ca2+ pump
Exchange transport
-Na+ leak in, Ca2+ out
-Ca2+ really wants to come in (electrical gradient and concentration gradient pulling it in)
- Can reverse direction in heart muscle cells every time the heart peats
- Diastole = Ca2+ pumped out
- Systole = Ca2+ leaks in
Digitalis
drug that blocks Na/K pump, allowing [Na+] inside cell to increase –> inhibits Na/Ca exchanger indirectly
H/K exchanger
Doesn’t exist!
Really is multiple transporters working in parallel
Two treatments for hyperkalemia
Encourage cells to take up potassium from the ECF
1) give glucose and insulin
2) give bicarbonate
