Flashcards in MCM Test 1 Deck (147):
What makes up a nucleotide?
Phosphate group, nitrogenous base, sugar
Which nucleotides are purines?
Which nucleotides are pyrimidines?
Thymine, Cytosine, Uracil
Between which molecules are phosphodiester bonds created?
Between a sugar (deoxyribose or ribose) and phosphate of the next nucleotide.
What is mRNA?
Messenger RNA. Transcribed from DNA and will be translated to a protein. Carries genetic code for protein.
What is rRNA?
Ribosomal RNA. Structural and functional components of the ribosome.
Which carbon contains or lacks a -OH group that characterizes the sugar as a ribose or deoxyribose?
2' carbon. Deoxyribose has -H while ribose has -OH at 2' spot.
What is tRNA?
Transfer RNA. Helps incorporate amino acids into polypeptide chain.
Where is pre-modified RNA found in a eukaryote?
Where is a N-glycosidic bond formed?
Between nitrogenous base and sugar.
What is RNAse H?
Machinery in DNA replication.
Replaces RNA primer with DNA
When a cell is tagged to no longer duplicate
Related to telomeres degrading into coding DNA
contains 8 histones wrapped by DNA.
Heterochromatic v Euchromatin
Heterochromatin- condensed, silenced genes
usually on periphery of nucleus
Euchromatin- accessible to transcription/replication
Histones have tails that can be modified to change chromatin structure
Modifications passed down
proteins maintain histone changes.
How is RNA polymerase different from DNA polymerase
can start without primer
has intrinsic helices function
is more error prone
Types of RNA Polymerase
RNA Polymerase 1= rRNA
RNA Polymerase 2= All protein coding genes
RNA Polymerase 3= tRNA
remember 123 RAT= rRNA, All, tRNA
TFIID- recruiter first and contains TATA binding protein (TBP), activates RNA poly II --> TFIIB, TFIIF, TFIIE, TFIIH
TFIIH- phosphorylates SER 5 on RNA Pol tail which initiates it.
other factors fall off and RNA Pol is released from promoter.
Methylated guanine cap added to 5' end
RNA pol carries proteins that are transferred at specific time.
Capping protein- binds to tail when SER 5 is
Phosphotase- removes Pi from 5' end
Guanine transferase- adds GMP
Methyl transferase- adds methyl
specific A in intron attacks 5' end and covalently bonds
3' exon end will attack 5' of other part
GU and AG are coming beginning/end of intron
protein and RNA molecules
Assists with splicing.
Poly A tail
RNA poly II recognizes poly A and cleavage signals
cstF and CpsF travel with RNA poly and get transferred to 3' end
CstF= Cleavage stimulating factor
CpsF= cleavage and polyadenylating factor
additional poly A bind proteins attach add length and shape
What does a mRNA need to be transported out of nucleus?
Nuclear export receptor
Bind to specific DNA upstream of promoter
DNA binding domain- binds specific DNA sequence
Activation domain- interacts with transcription factors
to initiate transcription
What are 3 ways to regulate transcription?
activators- bind to certain sequence to induce transcr.
repressors- bind to certain sequence to repress gene
Chromatin remodeling- change chromatin condensation
ex. HAT and HDAC
Histone acetyltransferase- coactivator adds acetyl group to histones to regulate transcription, accessible chromatin
Histone deaceytlase- corepressor, remove acetyl, condense chromatin
CG base pairs with methylated cytosine= condensed DNA
part of DNA methylation
dsRNA cleaved, finds complimentary strand and silence it
3 periods of embryonic development
Early period- 0-2 weeks, low sensitivity, high mortality rate
Embryonic period- 3-8, high sensitivity, organs being made
Fetal period 9-38 weeks, decreasing sensitivity, functional growth
What kind of cells are created from meiosis 2?
when does cross over take place
prophase 1 of meiosis 1
Origin of gamete forming cells?
Primordial germ cell arise from epiblast (week 2)
Migrate to yolk sac (week 3)
Migrate to posterior abdominal wall to the genital ridge (week 4-6)
primordial germ --> spermatogonium --> primary spermatocyte (meiosis I) --> secondary sperm. (meiosis II) --> spermatid > mature spermatozoa
primordial germ > oogonium > primary oocyte STOP IN Prophase I
primary oocyte > secondary oocyte STOP in metaphase 2
if fertilized, meiosis 2 completes and becomes ovum.
primordial follicle, squamous cells thicken to granolas
primary follicle (once zona pell. forms)
Secondary follicle when antrum appears
Follicle matures midway through female cycle (day 14)
Graafin Follicle- when antrum grows and granolas
cells form cumulus oorphourus
Follicle bursts-- secondary oocyte goes to pelvic cavity
and picked up by timbre of tubes
Follicle becomes corpus luteum
When and Why does the antrum appear in follicular development?
Appears when it's a secondary follicle.
Because theca interna is secreting fluid.
name the Gonadotropins during female reproductive cycle and what they effect.
FSH- works on growing follicle, ovulation
LH- maturation of follicle, ovulation, corpus luteum
Where are certain GLUT transporters found?
GLUT 1- most cells (RBC, nervous)
GLUT 2- liver, B pancreas
GLUT 3- most cells
GLUT 4- skeletal, adipose--- insulin regulated
Normal blood glucose levels
range: 4-6 mM (72-110 mg/dL)
Absolute 5mM (90 mg/dL)
glucose --> glucose-6 phosphate
inhibited by G6P
In liver with hexokinase (does same thing)
Inhibited by G6P, but insulin can override that
Phosphofruktokinase-- rate limiting enzyme for glycolysis
Fruktose 6P > fruktose 1, 6 bisP
high levels AMP, lets process happen
High levels of ATP or Citrate will inhibit enzyme
In liver, if PFK-I is inhibited it can turn it on
Insulin turns PFK II on, fructose 6P > fructose 2,6 P
fruc 2,6P turns PFKI on.
Glucagon inhibits PFK II
PEP > Pyruvate, creates ATP (substrate level phosphorylation)
Most common deficiency in glycolytic pathway
Why do we need two pathways in red blood cell
Glycolysis- provide ATP, Cation transfer, membrane impaired
HMS- Provides NADP, picks up electrons (now NADPH) so metHb > Hb and can bind oxygen
Role of 2,3 BPG in erythrocytes
increases oxygen release because it lowers Hb binding affinity for O2.
enhance oxygen delivery in
Two steps to charge tRNA?
what is the enzyme?
1. ATP hydrolysis to add AMP to amino acid
2. amino-acyltrnatrnasynthetase adds AA to tRNA
Antibiotics that bind to SMALL subunit of ribosome?
Antibiotics that bind to LARGE subunit of ribosome?
Initiation of translation?
met tRNA and small subunit find concuss sequence, initator factors
slide to find AUG
Large subunit joins
Termination of translation?
Reach stop codon, release factor binds to A site, Water added and breaks chain, machinery dissociates
Chaperone (heat shock) proteins
HSP70- fold cotranslationally, binds to hydrophobic and assits folding, has a backup system, uses ATP
HSP60- capsule like, post translational, has hydrophilic inside to help place hydrophobic in middle. uses ATP
Calmexin- chemical modification, uses glucose, if improperly folded adds glucose and does it again
19-S cap contains unfoldases
cylinder chops it up
How to mark protein for destruction?
1. Activate enzyme to add ubiquitin
2. use degradation signal-- phosphorylation, unmasking
Unfolded protein response
Creates cascade that turns genes on for specific chaperone
what happens in cell during G1/S phase
Mitogen > G1/S cyclin > binds to G1/S Cdk > phosphorylates Rb > releases EIIF (transcription factor)> turns on genes.
What happens during S phase of cell cycle
S cyclin produced > activates S Cdk > Phosphorylates ORC > Releases Cdc6 > origin site open for replication machinery
1. M Cdk Phosphorylates- lamin, cohesin, condensin
2. MCdk turns on proteins to trigger microtubule arrangement. centromeres duplicate, polarize, attach to chromosomes
3. Chromosomes line up at metaphase with different microtubules
4. MCdk phosphorylates APC > degrades securin > releases seperase > cleaves cohesin
5. Telophase: RhoA > ROCK and formin> actin and myosin> contractile ring assembled.
What are the 3 types of protein transports?
Gated- cytosol to/from nucleus
Transmembrane- cytosol to anything except nucleus
Vesicular transport- between organelles
Describe Gated transport (import)
Through nuclear pore complexes, uses Ran GTP. Protein needs nuclear localizing signal
Import- protein attaches to receptor, brought into cell. Ran-GTP attaches to receptor and displaces protein. Receptor moves outside and hydrolysis happens on cytosol face. Receptor now ready for new protein.
Describe transport out of nucleus.
Through nuclear pore complex. Uses Ran-GTP. Protein needs nuclear export signal.
protein binds with receptor with Ran-GTP. Moves through nuclear pore. Hydrolysis of GTP happens at cytosol face. Protein is unloaded and receptor goes back.
Describe import of proteins into the mitochondria.
TOM- outer membrane complex (has receptor attached). TIM 23- Inner membrane
TOM recognizes protein signal and binds to it. brings into intermembrane space, and also through TIM 23. Translocation to matrix.
Signal peptidase cuts signal off.
What is Signal Peptidase?
enzyme that cleaves signals on proteins once they are transported
Role of Pex19?
Help arrange peroxisome
Describe peroxisome import
Proteins have signal sequence, importin (enzyme on membrane) binds to sequence and imports protein
2 varieties of transport to ER.
Cotranslational- translated on rough ER put directly into ER
post translational-transcribed in cytosol, then moved to ER.
How does cotranslational transport happen
ribosome translating protein, SRP recognizes this sequence and binds. SRP receptor binds SRP/protein and feeds it to a translocation channel. two particles come off. protein moved inside and signal cleaved.
SRP- signal recogntition particle
SRP receptor- in ER membrane
How to get protein to ER membrane?
Protein has internal signal sequence. side (N or C terminus) closer to the + charged side will stick in cytosol.
Coated vesicle proteins and where they go.
Clathrin- from plasma membrane and between endosomal and golgi compartments. Receptors shoot inward and bind protein/adaptor. Bud off. membrane proteins surrounding vesicle may fall off.
COPI- early in secretory pathway. From Golgi
COPII- early in secretory pathway. From ER
How do vesicles bind to target?
Need: Rab GTP, Rab effector, V-snare, and tsnare.
1. Tethering. Rab GTP (on vesicle) interacts with Rab effector
2. docking. v snare (on vessicle) winds with t snare (target)
Rab directs to right spot on membrane. snares help with fusion
KDEL receptors-- help return proteins to ER. There are some in ER but more in Golgi
Proteins have higher affinity for KDEL in golgi than ER. Allows for retrieval to ER.
Describe retrieval of proteins to ER.
proteins need a KDEL sequence signal and bind to KDEL.
KDELs are in membrane of golgi and ER. Once bound it goes with vesicle, coated appropriately for transport.
How does the Golgi modify proteins for transport
Different processing happens in different compartments
Usually adds oligosaccharide to protein (covalent modification)
Transporting protein to lysosome
protein in golgi
1. Add Manose 6 phosphate
2. M6P receptor (on golgi membrane) binds it.
3. form vesicle (clathrin coat), goes to endosome> lysosome
LDL transport example
LDL receptors bud off and go back to plasma membrane before reach lysosome.
Specialized endosome recycling
GLUT 4 receptors example. Specialized recycling requires receptor on membrane
Insulin binds to receptor which stimulates GLUTS to bud from endosomes and go to plasma membrane.
Types of exocytosis
Constitutive- not regulated, always happening. Ex. replenish plasma membrane cells.
Regulated- something is packaged but needs hormone stimulation before it will be released. ex. neurotransmitters
1. signal mediated diversion to lysosomes
2. signal mediated diversion to secretory vessicles.
Protein folding road map
Folding > Maintenance > Aggregation > clearance by degradation
2 Quality Control Systems
1. Ubiquitin proteosome system: targets single proteins soon after ribosomal release
2. Autophogy(sp?) degrade proteins that are longer lived, targets aggregates..
2 major ways misfolding can cause dysfunction in cells.
1. Misfolded protein loses function> downstream effects cause symptoms.
2. Misfolded protein gains new function, forms aggregates. Leads to toxicity and loss of function
2,3- BPG what does it do?
binds to B subunit of Hb to help unload it.
PDH- takes Pyruvate (3C) to acetyl CoA(2C) by redox
also produced: NADH and CO2
AcetylCoA inhibits Pyruvate Dehydrogenase
Who needs these
PDH, and a ketoglutarate dehydrogenase
What inhibits PDH?
What inhibits the glycolysis enzymes?
PFK-I- ATP and citrate
pyruvate kinase- inhibited by ATP
What enzymes do I need to know from TCA?
a- ketoglutarate dehydrogenase
isocitrate > a ketoglutarate
makes NADH + CO2
Inhibited by ATP and NADH
Very important because it is regulated by ATP, NADH
a-ketoglutarate > succinyl coA
makes CO2 + NADH
lactase. Lactose > galactose
Lactase found in brush border of intestine
Galactose > galactose-1-P
Galactose-1-P + UDP-Glucose > Glucose1P
Fructose from Sucrose disacc. (table sugar, honey...)
Fructokinase= Fructose> fuctose 1P, use ATP
Brush border enzyme
Aldolase B= Fructose1P > Glyceraldehyde + DHAP
then on to glycolysis...
alcohol > acetalaldehyde
acetaldehyde > acetic acid
Both enzymes produce NADH
Acetaldehyde build up: nausea, vommiting, flushing, hypotension, headache (hangover smptoms)
Chronic alchohol consumption accummulates NADH, effecting major pathways. and major cause for alcohol related problems
Three ways Glucose 6P can go?
Pentose phosphate pathway (HMP shunt)
Where is glycogen stored?
Glc > glucose6P > glc1P > UDP Glu > glycogen
enzymes glucose 1P uridyl transferase
glucose 6P>UDP glucose
UDP Glucose > glycogen
forms a 1,4 linkage
Activated by insulin
Adds a1,6 linkage to branch
Branched version more water soluble , more accessible ends
Glycogen > G1P > G6P > Glucose (liver) or Pyruvate (muscle)
Glycogen phosphorylase-- breaks a1,4 bonds
glycogen debranching Enzyme: breaks a1,6
Phosphofructomutase: g1P > g6P
Glucose6phosphotase- (liver, turn g6P to glucose)
Roel of Transcription factors
TFIID- recognized TATA box, with TATA binding protein
TFIIF- (stabilizes) polymerase
TFIIH- Unwinds DNA
What activates/promotes glycogen phosphorylase and deb ranching?
Glucagon (acts in liver and adipose)
AMP muscle (low ATP)
Where does the Carbon come from to form glucose during gluconeogenesis?
1. Pyruvate or Lactate
2. Alanin (amino acid)
3. Glycerol (TG breakdown)
Where does pyruvate go in order to start gluconeogenesis?
Pyruvate > oxoloacetate > PEP
Pyruvate carboxylase (mitochondria)- Pyruvate to OAA
Activated by AcetylCoA
PEP carboxykinase (cytoplasm)- OAA to PEP
Activated by glucagon and cortisol
Fructose6-bisphosphatase (cytoplasm)- F1,6bisp > F6P
activated by ATP, inhibited by F2,6bisP
What does Pyruvate carboxylase need?
ATP (beta oxidation usually provides this)
Muscle: Glucose > Pyruvate > lactate
lactate moves to liver
Liver: lactate > AcetylCoA > pyruvate > glucose
G6P needs NADH from the reaction that makes acetylCoA
Glucose Alanine cycle
Muscle: Glucose > pyruvate > alanine
Liver: Alanine > pyruvate > Glucose
What is Hexose Monophosphate Shunts job?
Ribose sugar for nucleotides (Ribose-5-P)
NADPH (reducing molecule)
What are the enzymes in HMP shunt?
G6P > NADPH + 6 phosphoglucanate
ribose 5P > glyceraldehyde 3P
gives electrons to make water from superoxide?
needs electrons from NADPH to keep working
Why do heinz bodies form?
H2O2 (hydrogen peroxide) accumulates and denatures hb = heinz bodies.
How does G6PD deficiency relate to hemolytic anemia?
NADPH not there to donate electrons to make water from superoxides.
hydrogen peroxide builds up and denatures membrane
Episodic G6PD deficiency
only 50% of the enzyme G6PD is active. When body is stressed it will have episodic hemolytic anemia.
Start of gastrulation
Epiblasts migrate through groove to differentiate into three germ tissues
Primitive (Hensen's) node
form at cranial end of primitive streak
Organizer- helps form longitudinal axis.
Forms the tissues that form notochord, epiblasts pass through the node.
to form three germ layers
1. endoderm(deep)- epiblasts pass through spreak and displace hypoblasts
2. mesoderm(middle)- epiblasts invaginate.
3. ectoderm(superficial)- remaining epiblast cells
Primitive node gives rise to prechordal mesoderm
Invaginates node and gives rise to prechordal plate mesoderm
Some prechordal mesoderm mix with hypoblast to form a solid notochord
notochord is inducing structure for axial skeleton
Notochord will be next to ECTOderm, and induces thickening of ectoderm to form the neural plate, or neuroectoderm
The neuroectoderm give rise to the central and peripheral nervous system and neural crest cells.
What does the neural chord persist as in an adult?
Nucleus pulpous of the intervertebral disc.
Lateral fold: (day 21 start)
Cephalocaudal fold: (day 17is)
epidermis, hair, nails
Glands: sweat, sebaceous and lactiferous
Sensory epithelium of ears, nose, tongue, lens of eye, membranous labyrinth ear
Neural tube (neurulation)
Neural crest; PNS, retina
Somites; bone (vert column); ribs; skeletal muscle;
dermis; tendons and ligaments; cartilage
Urinary and reproductive tissue
Connective tissue, muscle, body wall, some viscera
*Mesoderm: vertebral column formation and all of our bones
Lining of GI tract
Inner epithelium of the respiratory tract, bladder, urethra
Week 9-12: Growth of head begins to slow, site of blood formation shifts from liver to spleen, week 12: external genitalia can be distinguished,
Weeks 13-16: rapid growth, hair on scalp, eye and eye movements
Week 17-20: limbs reach proportion and there are movements, skin covered in wax(protection), lanugo (hair covering), testes begin to descend, brown fat formed.
Week 21-25: weight gain, SURFACTANT beginning to be secreted, blink startle reflex, and fingernails form. EARLIEST FOR SURVIVAL
Week 26-29: Lungs capable of breathing, CNS can control breathing/temp, white fat formed, toenails develop, Week 28 blood production moves to bone marrow
Week 30-35: pupillary light reflex, fat accumulating 8% of weight is fat
Week 36-38: 16% body weight is fat, head large but closer to proportion, testes reached scrotum.
Maternal Serum Screening Test
Part of Assessing Fetal Status
AFP is secreted by fetal liver, leaks into blood stream. Mom blood samples taken to look at this level and combine it with other 2nd trimester markers (ex. hCG levels) to asses possible abnormalities.
AFP = Alphafetoprotein
Part of Assessing Fetal Status
Aspirate amniotic fluid to karyotype it, PCR and genotyping can be done to assess genetic abnormalities.
Performed after week 14 to prevent fetal harm, fetal loss risk 1/300-500.
Chorionic villus Sampling
Part of Assessing Fetal Status
Sample chorion frondosum (derived from embryo), fetal DNA can be harvested without harm to fetus
Slightly higher risk then amniocentesis
Guided by ultrasound.
What tells the primary oocyte to go through meiosis 1?
LH. Until this point primary oocyte is suspended in prophase 1.
Capacitation, enzymes in uterine secretions remove glycoprotein coat
Find each other: Sperm tail, uterine tube cillia and signal released from oocyte and surrounding corona help sperm find egg. .
1. Penetrate corona radiata
2. acrosome reaction (acrosome fuse with zone pep. make tunnel)
3. Penetrate Zona Pellucida
4. Fusion of oocyte and sperm cell membranes
5. Sperm enters cytoplasm, ZONA REACTION (no more sperm in cells)
6. Resumption of meiosis 2
7. Female pronucleus
8. metabolic activation of egg
9. male pronucleus
10. Nuclei merge
11. Cleavage begins.
16 cell (blastomere cells) inside zone pellucida
Zona pellucida stays same size while cells get smaller on division
Day 4. Fluid filled space forms between morula cells
Trophoblasts- cells that form outer ring of blastocyst
Embryoblasts- small mass of cells, will form embryo eventually
Before implantation Zona Pell degenerates so blastocyte can implant on wall
What are events in first week of fertilization?
4. Morula formation
5. Blastocyte formation
6. implantation (around day 6)
Trophoblast differentiation Day 8-9
Trophoblasts differentiate into:
Cytotrophoblasts: mono nucleated cells that divide, migrate into syncytiotrophoblasts, lose cell membrane
Sencytiotrophoblasts:multinucleated cells. PRODUCE hCG and eyes and enzymes that break down extra cell matrix between endometrial cells. (so embryo can go deeper).
Embryoblast differentiation Day 10-12
Embryoblast differentiaties to epiblast and hypoblast
form bilaminar disc
Hypoblast migrate to cytotrophoblast cells and form primitive yolk sac.
Amniotic cavity, above epiblasts
Holes that form in syncytium at the same time blood vessels are getting closer and closer.
syncytiotrophoblasts will dissolve endothelium of vessels, blood will fill trophoblastic lacunae
What forms the connecting stalk?
Formed by extra embryonic mesoderm
Eventually forms umbilical cord.
estrogen and/or progestin prevent release of FSH/LH from pituitary, preventing ovulation.
Contraceptive pills- inhibit follicular development
Medroxyprogesterone acetate (Depo-Provera): Decreae GnRH
from hypothalums= no FSH/LH release
IUD's- kill sperm, create fatal environment
Levonorgestrel (Plan B)- inhibit ovulation, make sperm not go
Low sperm count: <15 mil/mL (normal: 15-300 mill/mL)
Poor sperm motility (<40%)
Occluded uterine tubes
Lack or loss of implantation
Ectopic implantation, Pouch of Douglas, tube, intestine
Decidulization (corpus luteum secreting progesterone to build up wall) will happen as long as syncytiotrophoblasts secrete hCG.
Function of placenta
exchange metabolic and gas products
Nomenclature of placental development Mom v Baby
villi in embryology
fingerlike projections that extend towards blood supply
fetal part of placenta
Mother part of placenta
accreta= through stratum baseless
increta= into myometrium
percreta= all the way through
alphabetical for increasing severity
Placental circulation (vein v artery) ??
maybe google this, youtube?
Primordial germ cells migrate from here.
Blood cell devo. from weeks 3-6.
Provide nutrients during establishment of uteroplacental circulation.