Fall 2018 MCM Midterm Flashcards
Ether
Molality
moles solute / kg solvent
mol/kg
Molarity
Moles of solute/Liters solution
Facilitated diffusion
Facilitates down concentration gradient
Carrier mediated transporter
no energy needed
Facilitated diffusion rate of diffusion is _______
Limited
Vmax is limited, compared to passive diffusion
Primary active transport require…
ATP
Na+ K+ is an example of what kind of transporter
Active transporter
Na+K+ atpase moves sodium… where and potassium… where?
It moves 3 sodium out of the cell
It moves 2 potassium into the cell
Calcium concentration is greater _____ the cell?
outside
extracellularly
What kind of pump is the calcium transporter?
Active transporter
Secondary transport transports by
using energy but not ATP
concentration gradients or symport/antiport
Type I diabetes
no insulin produced
Type II diabetes
Sub obtimal response to insulin
Buffer consists of
weak base and conjugate base
Ligase
Forms bond between two by cleavage of ATP
apoenzyme
The protein part of a complex enzyme or of a holoenzyme
Holoenzyme
cofactor and apoenzyme
Lipid bilayer is composed of (3)
phospholipids
Sphingolipids
Cholesterol
Phospholipids are composed of
Philic head
Phobic tail
In general lipids can be 5 things
structural
antioxidant
substrates
resevoirs
hormones
Arachidonic acid
PRecursor to eicosanoids
Acid with fatty acid chain
SIGNALING (secondary messenger)
EPA name
Arachidonic Acid
Basic AA
Arginine (R)
Lysine (K)
Histidine (H)
Polar AA
Glutamine (Q)
Asparagine (N)
Serine (S)
Cysteine (C)
Threonine (T)
What’s significant about serine?
It has sulfur and can make disulfide bridges
Acidic AA
Aspartate (D)
Glutamate (E)
Aromatic AA
Tyrosine (Y)
Phenylalanine (F)
Tryptophan (W)
Nonpolar AA
Alanine (A)
Valine (V)
Isoleucine (I)
Leucine (L)
Methionine (M)
Proline (P)
Glycine (G)
What’s significant about methionine?
It has a Sulfur
Polar AA can bond what way?
Hydrogen bonds
What are the hydrophobic AA?
Nonpolar and aromatic
Ribozyme
RNA molecule acting as an enzyme
IU
internation unit
umol/min
High Km
Low affinity
Paracrine signals
Signals between two different cells at short distance.
Autocrine Signals
Siganls between two same cells nearby
Endocrine signals
Long distance signalling to target cells
Contact Signals
signalling through cell to cell contact
Skeletal has what kind of acetylcholine receptors
nicotininic
Cardiac M. has what kind of acetylcholine receptors?
muscarinic
Glut4 is found in
muscle and adipose
GLUT 2 is found in
hepatic cells
Glut 2 is ______ of insulin
independent
Glut 4 is ______ on insulin
dependent
Glut 1 and 3 is foudn in the
Brain
Glycogen storage found mostly in
liver and muscle
What is the final product of glycolysis
Pyruvate
or lactate
Hexokinase vs Glucokinase Km
Hexokinase Low Km
Glucokinase high Km
Phosphorylated Glucose
Can’t leave the cell
A phosphorylating enzyme step is…
irreversable
Caloric content of
Fat
Alcohol
Carbohydrate
Protein
9
7
4
4
Five secondary messangers
cAMP
cGMP
Ca2+
Diacylglycerol (DAG)
Inositol triphosphate (IP3)
Ester
Amide
D and L sugars
LSDRu??
L and S counterclockwise
Steroid precursor
Cholesterol
What is pyridoxine?
Vitamin B6
What is cardiolipin?
On inner layer of mitochondria, makes plasma less permeable. Phospholipids with 4 chains
Mitochondrial DNA described
Circular, double stranded
Mitochondrial genetic patterns
Does not follow mendelian genetics
Where are ribosome subunits synthesized?
Nucleuoli
Where are ribosomal proteins produced?
cytoplasm
Golgi apparatus - cis face
cis face is near the RER
Where does phosphorylation and glycosylation occur of recently synthesized proteins?
Golgi Apparatus
Phagosomes function
fuse with lysosomes, digest material
Pinocytotic vesicle steps
Clathrin coating
Fuse with early endosome
Early endosomes and late endosome locations
Start near cell membrane,
End near nucleus
How does cholesterol get into the cell?
LDL + Cholesterol travel to cell
Ingested by endosome
Cholesterol released to cell
IF you had vvv or disfuncitoning LDL receptors what which circulatory disease would you be predisposed to?
Atherosclerosis
Which enzymes assist inside of lysosome?
Acid Hydrolase
Intermediate filament function
Protect the cell structurally from shearing or stretching
Intermediate filament structure
Multiple stranded rope providing strength
Intermediate filament classes
Keratin
Desmin
Vimetin
Neurofilament
Nuclear Lamins
Two kinds of actin
F-actin (filamentous)
G-Actin (Globular)
Actin role in cell cortex?
^^^ amounts of actin in cell cortex, thin layer underlying cell membrane.
What filament binds to integrins and what do integrins do?
Actin
This allows binding to extracellular proteins
Myosin is compromised of?
actin
Actins role in wound healing?
Actin is used by fibroblasts to pull on wound to seal it
Intermediate filament structure
Circular 13 tubular proteins of either alpha or beta binding to counter alpha or beta part.
Which way do intermediate filaments grow?
from the centrosome “-“ site to the “+” direction
Microtubule stability?
Unstable
Half life of minutes
3 Microtubule functions
Stability
Intracellular movement
Seperate chromosomes (mitosis)
What does the MAP kinesin do?
the microtuble associated protein will walk to the + end or cell outside
What do MAP dyneins do?
Walk toward - end or center of cell
Common polar heads for phospholipids
choline
serine
ethanolamine
inositol
glycerol
Name
Phosphatidylcholine
Name
Sphingomyelin
Name
Ethanolamine
Name
Serine
Name
inositol
Name
Glycerol
Lecithin (a phosphatidylcholine) is used for?
Diagnosing fetal diagnostics (lung maturity)
Rhizomelic Chondroysplasia punctata
Problem
Symptoms
Mutation preventing plasmalogens in peroxisomes
Skeletal abnormalities
Distinctive facial features
respiratory problems
intellectual disability
PIP2 is an example of what? Function?
An inositol
Signaling
Phosphatidylserine role
Apoptosis
It will flip in membrane and signal apoptosis
What is glycerols role in fetuses?
Plays a role in surfactant, used to measure surfactant
Precursor to Cholesterol
Acetyl CoA
Spherocytosis
Physiological presentation
Symptoms
Rigid misshapen cells
Jaundice, gallstones, vvv RBC, enlarged spleen
GLUT-1 Deficiency syndrome
vvv blood sugar in csf
^^^^ mental retardation and seizures
Selenocysteine is foudn in proteins with what kind of activity?
Antioxidant
Which amino acid helps stabilize proteins?
Cysteine through disulfide bridges
What is the difference between cystine and cysteine?
Cystine is two cysteines connected by a disfulide bridge
How do hydrophobic AA interact with one another?
Through van der waals interactions
How are secondary structures held together?
Hydrogen bonds
What are the secondary protein structures?
alpha helice
beta sheet
beta turn
random coils
(beta turn and random coils are not consistent, but sporadic)
What is the g protein coupled receptor made up of?
7 transmembrane alpha helices
Ligand domain
Cytoplasmic domain (attaches to G proteins)
3 examples of quaternary proteins?
hemoglobin
heterotrimeric G-proteins (alpha beta gamma)
Type II collagen
What does Hsp70 do?
Heatshock protein 70 binds to the end of a protein to prevent premature folding
What does Hsp60 do?
Heat shock protein 60 folds protein using ATP
alpha 1 - antitrypsin deficiency
MUTATION causes the protease inhibitor to build up in liver (cirrhosis and dysfunction), and doesn’t reach lungs, causing lung problems
Creutzfeld-Jacob Disease
comes from MUTATION (5-10%), sporadic (85%), and acquired (mad cow)
^^^ # of denatured prions in brain
^^^^ # of B sheets
Amyloidosis
Cause
Aggregation of misfolded proteins as a result of PROTEOLYTIC CLEAVAGE and fragmentation of proteins.
AA Amyloidosis
Cause:
Leads to:
Precipitation of amyloid A fragments
Rheumatoid Arthritis
AL Amyloidosis
Causes
LEads to:
Precipitation of Light chain antibody.
Multiple Myeloma (cancer of antibody producing cells)
Alzheimers Disease (AB amyloidosis)
Precipitation of B-Amyloid (amyloid precursor protein)
Brain degeneration
Glucose 6 P Dehydrogenase Disease
Proteins in RBC are damaged by O2 free radicals, protein fragments preceiptate in RBC (heinz bodies)
OXIDATIVE DAMAGE
Non competitive enzyme inhibitor
Lower Vmax
Same Km
Competitive Enzyme inhibitor
Same Vmax
Lower Km
Uncompetitive enzyme inhibitor
Lower Vmax
Lower Km
Adenylyl Cyclase
ATP into cAMP
Protein Kinase A (PKA) is turned on by
cAMP
What does hexokinase and glucokinase do?
Converts Glucose into Glucose 6-phosphate
What do dehydrogenases do?
Remove H+ (oxidation/reduction reactions)
Whats a kinase?
Enzyme transferring phosphate from ATP
Aldolase function?
Reversible
F1,6BP > G3P + DHAP
Osmolality of ECF and ICF
290 mOsm
ECF is __% of the body water
33%
Simple diffusion types
Passive diffusion
Channels
Pore
Proteosome function?
A protein complex that breaks down proteins that have been tagged by ubiquitin
Lipids with serine plasma membrane role?
Apoptosis
AMP relationship with energy
High AMP = low energy
What does pyranose and furanose look like?
‘forms of glucose pyranose is more common form
What are the super secondary structures?
Two of them are the leucine zipper and the zinc finger.
They are binding domains in transcription
Mucchopolysacharidoses
Inability to degrade glucosaminglycans
spingolipidoses
Inability to degrade plasma sphingolipids
Pompe Disease
Inability to degrade glycogen
Mucolipidoses II(I-cell)
Inability to deliver acid hydrolases into the lysosome
Angelman’s syndrome
INablity to degrade proteins in the cerebellum/hippocampus
Really happy and laughy
VHL syndrome
prevents degradation of hypoxia inducible factor subunits
HIF’s will be high > blood vessel formation > tumor/cancer
Acid extruders
What they do and examples
Get’s H+ out of the cell
Na-H exchanger
Sodium driven Cl-HCO3 exchanger
H/moncarboxylate cotransporter
Na/HCO3 co transporter
Acid loaders
Transports H+ into the cell
Cl- channels for HCo3 to leave
Proton channel
Cl-HCO3 Exchanger
Na/HCO3 cotransporter
List the functional groups involved in enzymatic catalysis.
Covalent Intermediates
Cysteine, serine, lysine, histidine
List the functional groups involved in enzymatic catalysis.
Acid base catalysis
Histidine, aspartate
List the functional groups involved in enzymatic catalysis.
Anion Stabilization
Arginine, serine, peptide backbone
List the functional groups involved in enzymatic catalysis.
Cation stabilization
Aspartate
Organophosphorus toxins (nerve gas, VX, Sarin) do what to body?
Covalently bind to achetylcholinase, which leads to acetyl coa build up in body
Phophorylation mostly targets which AA?
S, T, Y
They all have oh groups
What is feed forward regulation
increase of substrate
What is the main way to control long term cell volume change?
By making osmolytes
Sorbitol, inositol
Two examples of contact signaling
Gap junctions
Antibody presentation
Nicotinic ACh receptor action?
Na+/K+ channel
Muscarinic ACh receptor action?
G-protein linked receptor
regulates K+ channel
What steroids attach to type I nuclear receptors
Cortisone
Aldosterone
Progesterone
Testeosterone
What steroids attach to nuclear receptors type III
Estradiol
Type I and III nuclear receptors location, action?
located in cytosol
Bind to hormone in cytosol and dimerize, enter nucleus and effect dna transcription.
Type II nuclear receptor, what hormones use this route?
Thyroid Hormone
Vitamin D3
Retinoic acid
Fatty Acids
Type II nuclear receptor mechanism
Hormone binds to dimer in nucleus > Corepressor is released and coactivator is added > Transcription
Nitric oxide activates….
Guanylate cyclase
Nitric oxide passes freely past cell membrane, and activate guanylate cyclase, which does what?
guanylate cyclase activate cGMP which causes cascade and in this case results in vasodilation
What kind of receptor is adrenergic and what do they do?
G-protein linked protein
HR
Smooth M. constriction
Metabolism
What drugs work on adrenergic receptors?
Beta blockers. Antagonists of Beta adrenergic receptors.
Can treat arrythmia’s
What kind of receptor are glucagon receptors?
G-protein linked
What kind of receptor is there for muscarinic ACh?
In the heart, G-linked protein receptors
No secondary messengers though
What kind of receptor is there for rhodopsin?
G-protein linked receptor.
Senses light
What kind of receptors does dopamine act on?
G-protein linked receptors
Drugs that act on dopamine receptors are related to what illnesses?
Schizophrenia, Parkinsons disease, ADHD
Insulin has what kind of receptor?
Enzyme linked receptor
Activates cascade
What does protein kinase A do?
Phosphorylates, which either activates or deactivates enzyme
What does Gs subunit do?
Stimulates adenylate cyclase
increase cAMP
What does Gi subunit do?
Inhibits adenylyl cyclase
decreases cAMP
What does Gq subunit do?
activates phospholipase C
Increase DAG IP3 and Ca2+
What does Gt subunit do?
Increases phosphodiesterase
increases cGMP
Which hormones activate Gs subunit?
Glucagon
Epinephrine
ACHT
Which hormones activate Gi subunit?
Adenosine
PGE1
alpha 1 adrenergic cells are located where? mediate what mechanism?
muscle
vasodilation through use of phospholipase C, activating DAG, IP3 and Ca2+
Adenosine acts on which subunit?
Effect on cAMP and HR
Gi subunit,
decreases cAMP
decreases HR
Caffeine mechanism
Antagonist of adenosine receptors, therefore increases HR
JAK STAT receptors
Kind?
Which molecule uses this?
JAK does?
STAT does?
Enzyme linked receptor
Cytokines
JAKs are tyrosine kinases
STAT’s are signal transducers
Serine Threonine kinase receptors
Kind?
Used by?
Signal transducer that binds to receptor?
Enzyme linked receptor
transforming growth factor B family
R-SMAD
Tyrosine-Kinase Receptor
Type?
Used by?
Signaling pathways it can activate?
Enzyme linked receptor
Insulin
MAP-Kinase, Phospholipase C, PI-3 Kinase
What does MAP-Kinase do?
Activates transcription of genes involved in glucose metabolism
What does PI-3Kinase do?
Shuttles GLUT-4 to membrane for insulin
What does PLC do? (phospholipase Kinase C)
Starts lipid and glycogen synthesis
Precursors of Eicosanoids
AA, Linoleic Acid, EPA, DHA
Eicosanoids act through which receptor?
GPCR’s
omega6:omega3
difference?
Ratio?
Omega 6 is more inflammatory and more stable
Healthy ratio is 1:1 - 4:1
Four major classes of eicosanoids?
Prostaglandins, leukotrienes, thomboxanes, Lipoxins
Phosphorylase versus phosphatase?
Phosphorylase adds phophate
Phosphatase removes phosphate
Kinase role
add phosphate from atp
Synthase mechanism
Adds two molecules without ATP
Phosphodiesterase interaction with cAMP
Converts cAMP into AMP
Epinephrine acts through what two receptors, and what do those receptors do?
Beta 2 adrengergic receptor (activates adenylyl cyclase)
Alpha 1 adrenergic receptor (activates PLC-2 > ca+ >glycogen degradation)
Glucagon’s relationship with muscle glycogen metabolism
It has not effect
Calciums relationship with glycogen metabolism
Ca++ release from excercise stimulates glycogen degradation
Ca2+ Calmodulin purpose
Stimulate glycogenolysis in muscle
High AMP means what?
low energy
Deficiency of omega-3’s affects…?
affects learning, memory, olfactory and auditory responses.
Leads to depression and aggression
PLA2 is inhibited by..?
Glucocorticoids (steroids)
Cox1 Job
costitutively expressed to maintain normal physiology
Cox2 job
Inducible in response to stress signals, proinflammatory
Lipoxygenases are ?
Leukotrienes and Lipoxins
COX 1 and 2 pathway make what eicosanoids?
Prostaglandins, Prostacyclin, Thromboxanes
The one inhibitory eucosanoid
PGE2
(causes pain/inflammation in neurons)
Common precursor for prostaglandins
PGH2
When a prostaglandin or thromboxine releases Ca2+ as a secondary messanger, what is the effect?
Constriction
When a prostaglandin releases cAMP as a secondary messanger what happens?
Relaxation, dilation
TXA2 is what?
And what is it’s role?
Where is it produced?
TXA2 is a thromboxane, it causes aggregation of blood clotting factors and vasoconstriction
Platelets
NSAIDs do what to Cyclooxygenase
Inhibit
What are resolvins?
Produced from?
When especially produced?
Resolvins inhibit proinflammatory factors
Produced from EPA and DHA cox2
Especially produced in presence of aspirin
Lipoxins are what?
anti-inflammatory factors and stop carcinogenesis
Leukotrienes are what?
Where produced
Proinflammatory
5-lypoxygenase pathway
PGE2/PGF2 can do what?
induce labor
PGE1 is used to treat
ulcers
PGI2 is used to treat
pulmonary hypertension
PGF2a is used in treatment of
glaucoma
Endocannibinoids: Anandamine
produced by
effectan
Produced by transacylase
analgesic
Isoprostaines
Produced by:
Released by:
Used for:
Peroxidation of AA
PLA2
Measures oxidate stress.
PGD2 major site of synthesis
Mast cells
When will proteolysis occur for HMG-CoA?
High cholesterol, bile salts and sterols
Glucagon’s relationship with cholesterol synthesis
Inverse
When glucagon is high, cholesterol synthesis is low.
What is insulin’s relationship with cholesterol synthesis?
When insulin is high cholesterol synthesis is high.
Linear
What happens when HMG Coa Reductase is dephosphorylated?
It is active and cholesterol synthesis occurs
High sterols effect cholesterol synthesis how?
By inhibiting transcription of HMG CoA reductase
What do statins do?
competitively inhibit HMG CoA reductase, lowering cholesterol synthesis
alpha-ketoglutarate dehydrogenase AND PDC complex
activators
Lipoic Acid
FAD
NAD+
Thiamine Pyrophosphate
CoA
UCP involved in
UCP (thermogenin) is involved in heat production through brown fat cells, it causes a leak and disperses heat by uncoupling ETC
Carbon monoxide and cyanide inhibit
Complex IV
IF there was a genetic defect of Oxidative phosphorylation, which DNA would most likely have cause the error?
mtDNA
Less control and checks
Dinitrophenol
What does it do?
Its an uncoupler
It facilities diffusion of proton gradient across inner mt membrane
3 ketone bodies
acetoacetate
acetate
beta-hydroxybutarate
Alcohol effects on metabolism
increase in NADH
Stops TCA
Acetyl CoA turns to ketones
Main difference in peroxisomal beta oxidation compared to mitochondrial beta oxidation?
FADH2 is produced
MCAD deficiency:?
What levels are high?
Treatment
Hypoketotic and hypoglycemic at fasting
High C6-C10 acylcarnitine in plasma AND urine
High C6-C10 dicarboxylic acids in urine (due to omega-oxidation)
High carbohydrates and glucose
Who needs carnitine for transport into mitochondria? who doesn’t?
Long chain fatty acids > C12 need carnitine
Medium chain fatty acids do not need carnitine for transport
Defiencies of Carnitine metabolism consequences
Liquid droplet accumulation in the liver heart and skeletal muscle.
Primary Carnitine Deficiency
Plasma C(16-18) acyl carnitine levels?
Plasma free carnitine levels?
Urine free carnitine levels?
Carnitine not transported into the cell
LOW
LOW
ELEVATED in urine (it has no where to go)
CPTI (liver)
Plasma C(16-18) acyl carnitine levels?
Plasma free carnitine levels?
Urine free carnitine levels?
CPTI enzyme not able to combine the long chain fatty acyl coa to the carnitine and therefore the long chain can’t enter the matrix.
LOW (not made)
HIGH (doesn’t ever attach)
NORMAL
CAT deficiency
Plasma C(16-18) acyl carnitine levels?
Plasma free carnitine levels?
Urine free carnitine levels?
CAT is unable to bring in the fatty acylcoa-carnitine, AND recycle the carnitine
HIGH (can’t enter matrix, goes to plasma)
LOW (Carnitine gets placed on acycoa but never recycled)
NORMAL
CPT II deficiency
Plasma C(16-18) acyl carnitine levels?
Plasma free carnitine levels?
Urine free carnitine levels?
Unable to split fatty acyl carnitine, therefore it stays in that form. No Beta oxidation
HIGH (looks like CAT will still transport it out)
LOW
NORMAL
What does acyl coa dehydrogenase do?
It’s the first step it Beta oxidation
How to go from pyruvate to oxaloacetate (and eventually to phosphoenolpyruvate for gluconeogenesis)?
Pyruvate carboxylase
What will activate the PDC and alpha keto dehydrogenase?
NAD+
FAD
LIPOIC acid
thiamine pyrophosphate
CoA
What will inhibit the PDC complex?
Acetyl Coa
NADH
What phosphyrlation state should the PDC be in to be active?
What will active end product be?
It needs to be dephosphorylated
Acetyl CoA
What will Ca2+ do to the PDC?
And which way will the reaction go? (like what is the end product)
It will activate the phosphatase, which will dephosphorylate the PDC and ACTIVATE it leading to acetyl coa
Glucose 6 phosphatase role?
In gluconeogenesis convert G6P to Glucose
F1,6BPase Role?
Inhibited by?
Convert F16P to F6P
F26BP
Achetyl choline does what to the heart?
binds to muscarininc
which activates Gi subunit
VVV cAMP and HR
Also it opens K+ channels
chylomicrons, vldl, hdl, ldl differences
Chylomicrons and vldl transport TAG, chylo’s from small intestines, vldl from liver
HDL takes cholesterol away from cell to excrete
LDL moves cholesterol to cell
When is albumin used?
When fatty acids are being transported from the adipocyte to the liver
