B1 Test 1 Flashcards
(245 cards)
1
Q
Alveolar hyperventilation can cause what pH imbalance?
A
Respiratory alkalosis; concentration of C02 becomes too small and concentration of bicarbonate overwhelms it
2
Q
Be able to tell the difference between a strong acid and a weak acid. What roles does the Ka play in determining this?
A
Strong acid has a Ka value over 1. A weak acid has a Ka value less than 1.
3
Q
Define diabetic ketoacidosis. What are common symptoms of ketoacidosis.
A
_____________ is caused when the is insufficient insulin to usher glucose into the cells, so they start to starve. Since cells are starving the liver starts to metabolize fatty acids and produce ketone bodies. However none of these are able to be used as energy without insulin. Patients will often present as sluggish, comatose, rapid deep breathing, high glucose levels, ketone bodies present in urine and bloodstream.
4
Q
Define molality?
A
moles of solute/ 1 kg of solvent (moles/mass)
5
Q
Define molarity?
A
Moles of solute/ 1 liter of solution. (mass/volume)
6
Q
Define osmotic diuresis. What causes this condition?
A
____________ occurs when there is an extremely high osmolality of the glomerular filtrate (using due to the presence of glucose, ketone bodies, or other solutes in colllecting duct) that cause water to be brought across the concentration gradient and to be excreted in urine. This will lead to extreme dehydration.
7
Q
How do you calculate the pH of any solution?
A
pH= -log [H+]
8
Q
How does bicarbonate act as an effective buffer?
A
Bicarbonate acts as an effective buffer by providing a weak acid and its conjugate base to help stabilize the change in pH around the pKa of the weak acid. The pKa defines the pH where 50% conjugate base and 50% weak acid is present. Stabilization occurs as hydrogen ions can either be accepted by the conjugate base if pH drops to low or donated by the weak acid if pH climbs too high.
9
Q
How is the partial pressure of C02 related to the pH? What is the equation that explains this phenomenon?
A
The higher [CO2] the more acidic the pH will become. Increase in [CO2] lowers pH.
10
Q
How many liters of blood is contained within the normal human body?
A
5 liters
11
Q
In terms of pH stabilization, why is heavy breathing needed during exercise?
A
Heavy breathing is needed due to the accumulation of lactic acid and CO2. Heavy breathing exhales CO2 and lessens the concentration of H+ in solution, thus raising the pH back to normal levels.
12
Q
Water is a good type of solvent for what compounds?
A
ionic solvents, polar compounds
13
Q
What are 3 examples that can lead to a high anion gap? Why?Normal range of anion gap b/w 10-20mEq/L
A
1) Diabetic ketoacidosis 2) Heart Failure 3) Prolonged lack of oxygen (lactic acidosis)
14
Q
What are the major ways that the body regulates pH? List the main two respiratory mechanisms.
A
- Exhilation of CO2 will raise the pH as less free hydrogen ion are available. 2. Excretion of ammonium (NH4+)through pee raise the pH.
15
Q
What does is mean for a saline solution to be designated as D5?
A
5% Dextrose. Do not give to a diabetic patient.
16
Q
What enzyme is responsible for the conversion of CO2 + H20 to H2CO3 (Carbonic acid)?
A
carbonic anhydrase
17
Q
What is isotonic saline given to dehydrated patients instead of water?
A
To match the body fluid osmolality and not make cells explode from trying to match the concentration gradient.
18
Q
What is metabolic acidosis and what does it cause?
A
___________ is caused by a decrease in bicarbonate concentration and thus lowers the pH.
19
Q
What is respiratory acidosis and what can it be caused by?
A
_____________ is the accumulation of CO2 concentration in lungs/body which will decrease the pH. Can be caused by COPD, asthmapneumonia, and sleep apnea. (NOT BREATHING WELL)
20
Q
What is the equation for the anion gap? What is the normal range?
A
Anion gap= (Na + K) - (Cl- + HCO3-). Normal range is 10-20mEq/L or 8-16 when K is excluded. Potassium can often be excluded due to its small concentration.
21
Q
What is the Henderson-Hasselbach Equation and what is it used to find?
A
pH= pKa + log (base/acid)
22
Q
What is the major way that carbon dioxide is created in the body?
A
Major by-product of the Krebs cycle
23
Q
What is the name of rapid breathing caused by diabetic ketoacidosis?
A
Kussmaul respirations
24
Q
What is the normal pH reference range of blood? What is classified as acidosis/alkalosis?
A
The normal pH of blood is between 7.36-7.44
25
Why is carbon dioxide considered acidic? How does its concentration within the body contribute to pH restoration?
C02 is considered acidic because of the rxn C02 +H20 --\> H2CO3 --\> HCO3- + H+. Therefore due to equilibrium shift when more CO2 is concentrated inside the body it causes more hydrogen cation to be dissociated from carbonic acid, thus significantly lowering the pH. Breathing rapidly released CO2 from the body; thus lowering its concentration AND increasing the pH.
26
What is the protoplasm? What is it composed of?
The nucleus and cytoplasm, NO MEMBRANES. It is composed of 1) water (80-90%) 2)ions 3) proteins 4) lipids carbohydrates
27
What is the roles of chromosomes inside the nucleus?
They house the primary genetic material
28
What are two unique features of the nucleus membrane?
1) It is a 2-layer membrane that is a continuation of the rough endoplasmic reticulum 2) It is very holy, with lots of "protein based pores" that assist with communication.
29
1) What is Emery-Dreifuss Muscular Dystrophy? 2)What type of genetic inheritance does it display? 3)What mutation is responsible for the disease? 4) What are symptoms of those affected with this disease? 5) What is a common organ that is affected?
\_\_\_\_\_\_\_\_\_\_\_\_\_ is an X-linked dominant disease of the nuclear envelope that is caused by a mutation in the EMERIN (EMD) and the LAMININ (LMNA), which are both part of the nucleoskeleton membrane. These mutations disrupt the communication between the nucleus and the cytoplasm. This disease specifically affects STRIATED/INVOLUNTARY MUSCLES. Common symptoms are dilated cardiomyopathy, limb-girdle muscular dystrophy, stiff muscles, progressive muscle weakness and wasting. It also causes the walls of the heart to weaken and the chambers to enlarge; difficult to pump blood volume (leads to heart failure). Different from duchenne muscular dystrophy.
30
1) What is Progeria? 2)What mutation is responsible for the disease? 3) What are symptoms of those affected with this disease? 4) What is a common organ that is affected to cause death?
\_\_\_\_\_\_\_\_\_ is a nuclear envelope disease caused by a mutation in the laminin A,C gene. Specifically, this disease prevents the organization of chromatin during mitosis (growing stage). Symptoms of childhood onset of premature aging, growth inhibition, baldness, osteoporosis, arthritis. Eventually most patients die of cardiovascular complications in teenage years.
31
1) What is Restrictive Dermopathy? 2)What mutation is responsible for the disease? 3) What are symptoms of those affected with this disease?
\_\_\_\_\_\_\_\_\_\_ is a nuclear envelope disease caused by a mutation of laminin gene (A,C ZMPSTE24) which causes RIGED TRANSLUCENT SKIN, pulmonary hypoplasia (underdevelopment), impaired movements.
32
What is a unique feature of the nucleolus that is not shared by any other organelle?
It has no membrane.
33
What is the role of the nucleolus.
The _______ is responsible for transcription of the genes for rRNA. The small and large subunits of the ribosomes are also completely translated in the \_\_\_\_\_\_, and then transported to the cytoplasm.
34
An enlarged nucleolus is an indicator of what type of cell?
Malignant tumor cells (they produce large amounts of proteins/ribosomes)
35
What is the size of the human ribosome? What is the size of its component parts, large and small subunits?
This ribosome is 80s total; composed of 60s and 40S.
36
What is the first step of translation for every protein?
The association between MET-tRNA and the small 40S ribosome subunit. It attaches to the 5' end.
37
What enzyme mediates the formation of peptide bonds in translation?
peptidyl transferase (housed in 60S subunit)
38
What is the size of the bacteria ribosome? What is the size of its component parts, large and small subunits? Why is this advantageous for us in medicine?
Ribosome with 70S total; 50S and 30S. Can be targeted by a number of antibiotics.
39
What are ribosome-associated-particles (RAP) and where are their jobs?
\_\_\_\_\_\_\_\_\_\_\_\_ recognize labeling sequences of specific proteins and shuttle these proteins to specific docking sites on the RER. Docked proteins are then sent through the pores INSIDE the RER where further modifications take place including glycosylation.
40
Where are the majority of proteins produced?
In the ribosomes attached directly to the RER membrane.
41
What happens to proteins after they have been shuffled through RER by the help of ribosome associated proteins (RAP)?
Proteins will become glycosylated inside RER and are transported into the lumen of smooth ER (also known as transitional ER)
42
What happens to unlabeled proteins not recognized by RAP?
They stay on the outside of the RER and remain in the cytosol.
43
What happens to proteins after they are shuttled into the smooth ER? Do any other modifications of proteins take place?
Proteins bud off on the TRANS side of the smooth ER in TRANSPORT VESICLES and fuse with the CIS side of the Golgi apparatus. Modifications occur to the cis, trans, and medial cisternae oligosaccharide chains.
44
What happens to proteins after all modifications have been made inside the Golgi apparatus?
Processed glycoproteins then bud off the trans portion of the Golgi apparatus in SECRETORY VESICLES. These secretory vesicles will travel to predetermined sites.
45
Fragmented Golgi apparatus can be found in cells of what common disease?
Alzheimer disease patients demonstrate this type of modification inside their neurons. Pathological changes in this structure have also been identified in Huntington's and Parkinson's disease.
46
What are the main functions of the smooth ER? List 4.
1) Storage of calcium 2) Secrete proteins in transport vesicles to GA. 3) Involved in LIPID metabolism 4) Produce detoxifying enzymes
47
IP3 acts as a secondary messenger in the release of ______ from \_\_\_\_\_\_\_\_\_.
Calcium; smooth ER
48
What do Asp and Asn stand for?
Aspartate & asparagine respectively
49
What do Glu and Gln stand for?
Glutamate & Glutamine respectively.
50
What is Maple Syrup Urine Disease
This disease is caused an inability to catabolize branched-chain amino acids such as Leu, Ile, Val. (I Love Vermont) Since the enzyme ________ is missing to break down BCAAs, neurotoxicity buildup develops in bloodstream- untreated patient will suffer from mental retardation and high mortality rate. Treatment is to have diets that have low concentrations of BCAAs.
51
What is the missing/deficient enzyme in Maple Syrup Urine Disease?
[branched-chain alpha-keto acid dehydrogenase] is the missing enzyme in this disease
52
What is the missing enzyme in PKU or phenylketonuria?
this is a disease caused by a deficiency of phenylalanine hydroxylase
53
What is PKU or phenylketonuria?
\_\_\_\_ is a disease caused by the inability of phenylalanine to be converted to tyrosine. thus phenylalanine buildup causes neurotoxicity and will lead to mental retardation if left untreated. Treatment for this disease is a diet that avoids phenylalanine.
54
What amino acid serves as the precursor for serotonin?
tryptophan is the precursor for \_\_\_\_\_\_\_\_\_
55
What is SERCA pump?
It is the pump in the smooth ER that is responsible for pumping Ca2+ against it concentration into the sarcoplasmic reticulum (important for cardiac contraction)
56
What are clathrin coated pits?
involved in CME; multiple monomers of this substance congregate on the interior cellular membrane I response to a signal from receptor protein and help mediate entry into the cell (growth factors, receptors). Form basket around cargo. Depolymerization and formation of endosome occurs as acidification of vesicles occurs. pH continues to drop as one vesicle joins up with multiple other vesicles. Lysozymes are also added from Golgi vesicles but will only function at very low pH.
57
What is caveolae?
a multipass integral protein involved in transcytosis (for your neighbor)
58
What is the function of lysozymes and how do they do it?
\_\_\_\_ responsible for degredation of endycytosed material or phagotosized material. Contain of 40 different types of hydrolytic enzymes, hydrolase being the primary one. Hydrolases are originally produced in the RER then sent to the Golgi body which and a sugar, then send it to the lysosomes.
59
What is Tay-Sachs Disease? What enzyme is it missing? What are the symptoms?
\_\_\_\_\_\_ disease is caused by the congenital absence of the enzyme HEXOSAMINIDASE A (a lysosomal hydrolase). As a result way to much GM2 GANGLIOSIDE accumulates inside the lysosomes and causes symptoms such as 1) neurodegeneration 2) developmental delay 3) cherry red spot on macula 4) lysosomes with onion skin 5) DOES NOT EXHIBIT HEPATOSPLENOMEGALY(enlargement of liver and spleen)
60
What is Nieman-Pick Disease? What enzyme is it missing? What are the symptoms?
\_\_\_\_\_\_\_ is caused by the congenital absence of the enzyme SPHINGOMYELINASE (a type of lysosomal hydrolase). As a result sphingomyelin accumulates in lysosome. Can cause 1) Neurodegeneration 2)Foam cells (fat laden macrophages, indication of plaque buildup 3) Cherry-red spot on macula 4) hepatoslenoMEGALY
61
What is Gaucher Disease? What enzyme is it missing? What are the symptoms?
\_\_\_\_\_\_\_ is caused by the congenital absence of the enzyme GLUCOCEREBROSIDASE (a type of lysosomal hydrolase) which prevents the breakdown of glucocerebroside in lysosome. This can cause 1)Pancytopenia (reduction in RBC, WBC and platelets) 2) Necrosis of the femur 3) bone crisis 4) \_\_\_\_\_\_\_cells 5) Lipid-laden macrophages 6) heptosplenoMEGALY
62
What are the roles of peroxisomes? What is are their primary class of enzyme?
this organelle is involved with "cell cleaning". Its involved with 1) oxidation of cellular lipids 2) beta oxidation of fatty acids, 3)reduction of free radicals (hydrogen peroxide to water). This organelle contains CATALASES which convert hydrogen peroxide to water. 4)Also house enzymes involved in the pentose 5 pathway (energy metabolism) 5) important for the SYNTHESIS of phosolipd-plasmalogen (plasmalogen makes of 50% of hearts phospholipids and 85% of ethanolamine in myelin (brain tissue)
63
Zellweger Syndrome (Cerebrohepatorenal syndrome)
this is a peroxisomal disease caused by the absence of functional peroxisomes inside the cell. It is an autosomal recessive disorder that causes impaired neuronal migration and HYPOmyelination, which leads to progressive loss of hearing AND vision. Other symptoms include 1) cranial deformities 2)chondrodysplasia punctate 3) hypotonia (floppy baby syndrome) 4) seizures 5) apnea this disease usually causes death before 6 months old
64
ATP synthase
allows protons to come back into matrix form outer membrane, energy is captures to form ATP
65
What is Leber's Hereditary Optic Neuropathy
a syndrome that has point mutations on genes that encode for mitochondrial oxidation proteins. This disease effects young males primarily and causes degeneration of retinal ganglion cells (optic nerve atrophy) eventually leading to loss of vision in both eyes (8 weeks separated), Mother is the carrier of this gene (MITOCHONDRIA)
66
Myoclonic Epilepsy w/ Ragged Red Fibers
a syndrome that has point mutations on genes that encode for mitochondrial oxidation proteins. Symptoms include myoclonus (involuntary jerking of muscles), seizures, dementia, optic atrophy, neuropathy, arrhythmias. Usually multiple symptoms present at the same time. Mother is the carrier of this gene (MITOCHONDRIA)
67
How does cyanide kill you? What is an indirect way to get cyanide poisoning?
This toxin blocks all production of ATP by binding to cytochrome a3 subunit in oxidative phosphorylation of Krebs cycle. Causes death in about 6-8 minutes from cardiac arrest.
68
A patient presents with faintness flushing, perspirations, and hypernea (rapid breathing) and being involved in a house fire. What is a probable diagnosis and what is the treatment?
Mild cyanide poisoning. S.A.S Treatment includes: 1)sodium nitrite 2)amyl nitrite 3)sodium thiosulfate these drugs will convert cyanide into thiocyanate, which is significantly less toxic substance
69
osteogenesis imperfect
a disorder caused by the replacement of glycine by another more bulky amino acid in the formation of cartilage (and ultimately bone). Symptoms include blue (translucent) sclera, hearing loss due to funky middle ear bones, dental imperfections. -type I can often be mistaken for child abuse -type 2 cause prenatal death
70
What are the 2 (or 3) positively charge amino acids. List them.
1) Lysine (pka=10.5) 2) Arginine (pka=12.5) 3) sometime histidine (pka=6)
71
What are the 2 negatively charged amino acids?
1) Aspartic acid (aspartate) pka= 3.9 (ASP) 2) Glutamatic acid (glutamate) pka = 4.3 (GLU)
72
What are the 6 uncharged polar amino acids?
S.T.A.T.GC Serine Threonine Asparagine Tyrosine Glutamine Cysteine
73
These 3 amino acids can be used for N or O glycosidic linkages.
1) threonine 2) serine 3) asparagine glyosidic bond is helpful for the formation of glycoproteins, these are helpgul for Cell surface recognition etc.
74
\_\_\_\_\_\_ is a precursor for synthesis of catecholamines such as dopamine, epinephrine, and norepinephrine.
Tyrosine
75
What are the 4 main interactions involved with tertiary protein structure?
1) disulfide bonds (cysteine) 2) hydrophobic interactions 3) hydrogen bonds 4) ionic bonding (can only occur between two amino acids that are BOTH fully charged)
76
What is sickle cell anemia?
\_\_\_\_\_\_\_\_\_\_\_ is a blood disorder caused by a mutation on RBC that changes GLUTAMATE to VALINE. That changes to lifespan of the RBC from 120 days to ~20 days. Symptoms include episodes of pain (due to anoxia in capillaries) , chronic hemolytic anemia, and hyperbilirubinemia. Infected RBCs will also not travel as far on electrophoresis due to loss of negative charge from glutamate.
77
What are some common functions of glycolipids?
1) cell to cell interaction (cell receptor) 2) receptors for certain toxins 3) acts as antigens for different blood types
78
Transmembrane proteins usually have what type of secondary structure included in them?
Alpha helices
79
What are the two types of phospholipids found on the OUTER membrane?
1) phosphatidylcholine 2) sphingomyelin (Nieman-Picks Disease)
80
What are the three types of phospholipids found on the INNER membrane?
1) phosphatidylserine (memory!) 2) phosphatidyllethanolamine 3) phosphatidylinositol DRINK SUGARY PROTEINS, but they will kill you
81
What type of molecules need to be transported into cell using channel-mediated diffusion?
Small lipid insoluble substances
82
How does the Potassium (K+) channels work?
contain a tetrameric structure with a specific PORE LOOP that act as feelers to identify K+ specifically. Carbonyl oxygen then removes water from K+ and conformation change allows entrance into cell.
83
What effect does Fugu fish toxin (puffer fish) have on the cell and what symptoms does it cause?
this toxin blocks the voltage gated Na+ channels and prevents them from working. Without these voltage gated sodium channels, muscles contration is impossible, so it leads to paralysis. IT IS A SALT WATER FISH. IRONIC?
84
What are two of the unintended effects of the Na+/K+ pump?
1) It dries out cell b/c water follow sodium and positive charge to the outside of the cell. 2) it creates about 80% of the heat in your body
85
What is the job of topoisomerase I?
This enzyme relieves the supercoiling of DNA caused by helicase by making a nick on one strand. Involved in both the cutting and the reanealing of DNA.
86
What is familial hypercholesterolemia? What causes it? What are the symptoms? What is the difference between recieving a homozygous and heterozygous copy of the genetic disorder?
This disease is the result in the **mutation or absense of the LDL receptor** on the surface of the cell membrane. The LDL receptor is involved with the absorption and destuction of LDL. This mutation/absense causes excessive build of LDL which leads to **HIGH cholesterol levels**.
Symptoms include
* **xanthomas** (lipid deposits on skin)
* **heterozygous** inheritance will lead to MI in _adolescence_
* **homozygous** inheritance will lead to MI in _childhood_
87
What is a symport/cotransport? It it a passive or active transport? Give an example of a symport/co-transport.
A ______ is a type of mebrane protein that utilizes the concentration gradient formed by the Na+/K+ pump to serve it's purpose of sneaking a desired compound into the cell along with an ion flowing down it's concentration gradient. Both substances entering the cell require the **binding of a carrier protein**. For the reason a _________ it consider an example of **secondary active transport**. An example of this is **glucose/AA/Na+**
88
What is a antiport/counter transport? It it a passive or active transport? Give an example of a antiport/counter transport.
A ______ is a type of mebrane protein that utilizes the concentration gradient formed by the Na+/K+ pump to serve it's purpose of performing a **"classic switchero"**; and therefore is consider a type of **secondary active transport**. A carrier protein is required for this switchero. An example of this is **Na/H/Ca Counter transport. (dont need to know this example)**
89
What are the roles of selectively permeable channels? What bodily functions do they help perform? Give two example of selectively permeable channels.
There are two main types of \_\_\_\_\_\_\_\_.
1. **Voltage-gated channels**
2. **chemical/ligand gated channels**
Both of these _________ response to changes in the environment to let SPECIFIC types of molecules into/out of the cell. Two example are the Voltage-gated **Na+ channels** (think fugu/puffer fish) and **Ligand-gated K+ channels** (think tetrameric structure,pore loops (feel potatoes), dehydration), which are important for signaling between **neurons**, and activation of **muscles** cells
90
Finding this type of phospholipid on the OUTER layer of the cell membrane will trigger apoptosis.
phosphatidylserine
91
What is Wilson's Disease? What type of disease is it classified as? What causes it/gene affected? What are the symptoms? What is its genetic inheritance?
This disease follows a *autosomal recessive inheritance* (mutuation on ATP7B gene causes defect of _copper-dependent ATP-ase_) cells **can not secrete copper out of cells,** symptoms are caused by excessive buildup of copper (CNS, kidneys, eyes, liver). Classified as a cell membrane disease.
happens in active hepatitis, liver fibrosis, and cirrhosis
_Symptoms_
* tremors
* muscle stiffness
* personality changes
* anxiety
* hallucinations
hint: (volleyball cannot get copper out of it)
92
What is Cystic fibrosis? What type of disease is it classified as? What causes it/gene affected? What are the symptoms? What is its genetic inheritance?
\_\_\_\_\_\_\_\_\_ results in the drying out of many bodily organs/secretions. It results from the mutation of the **CFTR gene** and is **autosomal recessive**. A mutation in the CFTR gene leads to _defect in the Cl- membrane channel_ (CFTR protein.)
**Symptoms** include
* production of abnormally think secretions in the GI, pulmonary system
* salty-tasting skin
* difficulty breathing, coughing up mucus, pulmonary infections
* pancreative, liver, and renal insufficiency
* infertility in males
LOTS or ALL of these symptoms are caused because Cl- stays OUTSIDE of the cell due to broken membrane channel and pulls out its friend Na+. Water always follows (NaCl) and therefore you get many dehydrated products (alveoli, sprerm, etc)
93
What is one main structural difference between purines and pyrimidines?
Purines are DIcylic
Pyrimidines are cyclic
94
What is the difference between a nucleoside and a nucleotide?
Nucleo**SIDES** do not have any phosphates attached to the 5-carbon sugar. ONLY sugar and nitrogenous base.
Nucleotides include phosphate groups.
95
What type of bond joins nucleotides together in DNA?
phosphodiester bonds
96
What type of bond links 5-carbon sugars to their respective nitrogenous base?
Glycosidic bonds
97
What is the definition of Tm for DNA?
The temperature requires to melt 50% of the DNA in a sample (high GC content equal higher Tm)
98
What enzyme and class of enzyme are responsible for the supercoiling of prokaryotic and mitochondrial DNA. What class of antibiotic inhibit this process? Give two examples from this class of antibiotics.
DNA gyrase is responsible for supercoiling, and it is a type of topoisomerase II.
DNA gyrase and supercoiling can be inhibited by quinolones (quit coiling!). Quinolones end in "-floxacin"
Two examples of quinilones are
1. norfloxacin
2. ciprofloxacin
99
What is chromatin composed of?
DNA + histone +non-histone proteins
100
What are the names of the "small packing units" that make of chromatin?
nucleosomes
101
Which specific histones are used for the formation a the histone octamer? Which histone is used for linking histone octamers and formation of 30 nm fiber (nucleofilament)?
Octamer composed of **_2 COPIES_** OF H2A, H2B, H3, H4!
H1 is used in linkage between nucleosomes and formation of 30nm fiber (nucleofilament)
102
What are some notable differences between prokaryotic and eukaryotic mRNA?
eukaryotic mRNA has a 5' cap (m7G) and a 3' poly-A tail (50-200 adenine)
prokaryotic mRNA begins being translated as soon as it is transcribed
103
List 5 characteristics of tRNA.
1. The smallest of all RNA
2. becomes covalently linking to SPECIFIC amino acids based on.....
3. anticodon loop
4. CCA-3' terminus (site of AA attachment)
5. cloverleaf structure (some dsRNA, only RNA that contains a "T base" as a post-transcriptional modification)
104
What is the START codon?
What are the 3 STOP codons?
Start= AUG (think gun), codes for methionine
Stop= UGA, UAA, UAG
(U Go Away, U Are Away, U Are Gone)
105
What is the enzyme for attaching tRNA to the specific amino acid that it codes for? How does this enzyme work?
aminoacyl-tRNA-synthetases
works by forming covalent bond between tRNA 3' carboxyl terminal to 3' nucleotide hydroxyl group (ester bond)
pyrophosphate is cleaved from 3' CCA terminal yielding 2 high energy unit for CHARGING the tRNA.
106
What is the wobble hypothesis? What does this allow?
The 3rd nucleotide on the codon (or the 1st nucleotide on the anticodon) can sometime bind in non-traditional way
Allows one tRNA to recognize more than one codon
107
What are the 3 sites for translation on the ribosome?
**_A site_**: site for incoming charged tRNA
**_P site_**: site where tRNA carries current chain of amino acids
**_E site_**: exit site of tRNA
108
What are the energy requirements for translation?
2 ATP of used for CHARING tRNA
1 GTP is used for binding of charged tRNA to A site
1 GTP is used for translocation step
(4 high energy unit ***per AA*** + 1 for initiation + 1 for termination)
109
How is translation initiated in prokaryotic cells? What is recognized? What eukaryotic structure is this comparable to?
Prokaryotic translation is initiated by recognition of the SHINE-DALGARNO sequence. THIS IS NOT A PROMOTER SEQUENCE! Small ribosome subunit (30S) binds to this and 50S subunit waits for AUG to associate.
This structure is comparable to the 5' cap on eukaryotes
110
List 4 antibiotics that disrupt prokaryotic translation?
1) streptomycin (aminoglycoside)
2) erythromycin (macrolide)
3) tetracycline
4) chloramphenicol (can interfere with mitochondrial protein synthesis)
S.top C.losing E.very T.ranslation (site)
WE NEED PROTEIN!
111
What type of toxins are capable of disrupting translocation in translation? What is the name of the translocation factor they inhibit?
**_psuedomonas_** and **_diptheria_** can inhibit _________ by specifically inactivating **eEF-2 (eukaryotic elongation factor-2)**
Police Department prevent this.
112
Compare the origins of replication between eukaryotes and prokaryotes?
Prokaryotes= 1 origin of replication
Eukaryotes= multiple areas of replication
113
What protein is used in prokaryotes to establish an origin of replication?
20-50 monomers of DNaA protein
114
In prokaryotes, which enzyme is responsible for separation of dsDNA when it is time for replication? What time of proteins assist this enzyme?
DNA Helicase force strands apart and recieve help from ssbp (single stranding binding proteins) which keep DNA for reanealing and protect against nuclease activity.
115
Which class of enzymes are responsible for relieving tension on DNA caused by supercoiling? How do they act on the DNA to do this.
Topoisomerases are responsible for relieving supercoiling.
Topoisomerase I relieves tension but cutting nick on ONE DNA strand and religates it.
Topoisomeraes II relieves tension by cutting nicks on BOTH DNA strands and then religates them.
DNA gyrase is a type of topo II (causes supercoiling) which can be inhibited by quinolones (end it floxacin)
116
Why can't DNA polymerase begin DNA synthesis by itself. What enzyme does it need help from?
\_\_\_\_\_\_\_ is missing a free 3' hydroxyl group. RNA primase lends a hand and begins DNA synthesis by making the first ~10 nucleotides (cell will edit and replace these nucleotides later).
117
Briefly describe the action of DNA Polymerase?
DNA Polymerase uses the newly synthesized 3' hydroxyl to break bond on incoming nucleotide's 5' triphosphate to create pyrophosphate. Pyrophosphate is further cleaved to inorganic phosphate to prevent reverse reaction.
118
Which enzymes is responsible for elongating the leading and lagging strand in prokaryotic DNA? How much energy is required per nucleotide? How does it maintain accuracy? What is the response if a mistake is made in DNA synthesis?
DNA Polymerase III
Two high energy bonds are needed for each nucleotide that is added.
DNA Pol. III has proofreading ability, and if a mistake is made, 3'--\>5' exonuclease activity
119
Which enzyme is responsible for going back and removing all of the RNA primers that were used in the formation of Okazaki fragments?
DNA Polymerase I
It has exonuclease activity in BOTH directions. Replaces rNTP with dNTP. Still has not completely sealed DNA.
(DNA Pol. I holds up 1 finger annoyingly to remind there is work left to be done, bc RNA primers are still present in DNA)
120
Which enzyme fills in the nick in the DNA after RNA primer has been replaced by correct dNTP by DNA Pol. I?
DNA ligase
121
What is the role of DNA Telomerase?
What is it's role in cancer cells?
In linear DNA there will always be a 3' overhang after replication has been completed because there is not sufficient from for RNA Primase and DNA Pol III to bind to template strand and continue with synthesis. DNA Telomerase come along and adds addition nucleotide sequences to the template strand allowing for RNA Primase and DNA Pol III to continue work. Usually these sequenes are repeating and contain looks of AT pairs for easy access. Not all cells need/have DNA telomerase because it vastly extends the life of a cell. Cancer cells need telomerase so that they can replicate infinitely. Cancer even has way of ACTIVATING inactive DNA telomerase.
122
What is one of HIV's unique features?
It contains reverse transcriptase which allows virus to synthesize DNA from an RNA strand. Has very high rates of mutation because there is no proofreading ability. Telomerase also has some of this ability.
123
What is mismatch repair?
After DNA has been replicated certain proteins are able to scan the DNA for incorrect coding (mismatches in base pairing) and use endonuclease to nick the damaged strand and remove incorrect region.
124
What is Lynch Syndrome (hereditary nonpolyposis colorectal cancer, HNPCC)
a defect in mismatch repair does not allow for editing of newly synthesized DNA, which leads to an increase in mistakes. This causes cancer because replication can no longer be controlled.
-autosomal DOMINANT inheritance
Lynch= use colorectal to tie this :(
125
How can UV light affect DNA? How can this be fixed?
Can cause pyrimidine dimers (usually thymine dimers)
These are covalently links nitrogenous bases ON THE SAME DNA STRAND (one above and below) that make synthesis difficult for DNA Pol III.
Solution:
* excision endonuclease (UV-specific endonuclease) cuts DNA on both sides of pyrimidine dimer (thymine) and then it gets replaced by DNA Pol I.
126
What is xeroderma pigmentosum?
A genetic condition that in caused by a defect in excision endonuclease which leads to many skin tumors on areas of skin exposed to UV light.
127
What components make up the RNA Polymerase? What is the name of the completed RNA Polymerase?
1) **Core enzyme**- contains polymerase activy necessary for synthesizing DNA
* two alpha subunits
* one beta subunit
* one beta prime subunit
2) **Sigma factor**- responsible for finding and binding to promoter sequences. Sigma factor will dissociate from enzyme once transcription begins
together they form the **holoenzyme**
128
What are the two most famous PROMOTER sequences used for start of transcription?
1. TATA BOX (PRIBNOW BOX)
* -10 on coding strand before start of transcription at +1
* * -35 SEQUENCE
129
What is the energy requirement for adding each addition rNTP to the RNA strand?
2 high energy bonds cleaved, first pyrophosphate, then inorganic phosphate
130
What are the two way to that RNA transcription ends?
1) Rho-dependent termination- requires rho factor which displaces the DNA template strand allowing RNA Polymerase to dissociate
2) Rho-independent termination- require a G-C rich stem loop followed by a poly U stretch. G-C area will act as a lasso and pull off RNA polymerase
131
What is the action of Rifampin (rifamycin)? What disease does it treat?
\_\_\_\_\_\_\_\_ is a type of antibiotic that bind to RNA polymerase and prevent transcription initiation (probably by inhibiting action of sigma factor). It is know to treat tuberculosis.
RIPS off DNA. Think rope/lasso/tube (rho independent)
132
What is the difference between euchromatin and heterochromatin?
You USE euchromatin because it is more exposed. It is often more exposed due to acetylation of H1 histones, leads to beads-on-a-string model.
Heterochromation is more densly packed, and is HIGHLY methylated.
Methylation= turn off
acetylation=turn on
133
Which different RNA Polymerases are responsible for the creation of 1) rRNA 2) mRNA 3) tRNA?
RNA Polymerase I is responsible for the creation of rRNA
RNA Polymerase II is responsible for the creation of mRNA
RNA Polymerase III is responsible for the creation of tRNA
134
What is the equivalent to the TATA box in eukaryotes and what does it function as? What other sequence is important for initiation in EUKARYOTES?
1) Hogness box (-25), functions as promoter region
2) CAAT box (-70)
135
What post-transcription modifications are made to tRNA?
* splicing on intron loop
* trimming of 5' and 3' end
* switching U to T
* adding 3' CCA terminus (C is third letter)
136
Differences in transcription/RNA synthesis between prokaryotes and eukaryotes
1) prokaryotes begin translation during the process of transcription. Eukaryotes are seperated
2) post transcriptional modification occur in eukaryotes
3) 5' and 3' structures added to euk.
137
What is the purpose of 5' cap and how is it made?
What is the purpose of 3' tail and how is it made?
1) Euk 5' to 5' cap is made to signal recognition by ribosomes for translation.
Protects against nuclease degradation
Stabilizes molecule
2) poly-A tail serve as a signal for transport outside the nucleus, stabilizes mRNA
138
139
What is an intervening sequence? What is an intervening sequence called once it is removed?
Region of intron in immature RNA. Once it is removed from RNA it is called a lariat (looks like a lasso)
140
What is a spliceosome and what is it composed of? What do the different components do?
Spliceosomes are responsbile for cutting introns out of premature RNA. They are composed of snRNPs which IDENTIFY splice sits. The snRNAs are subunits of the snRNPs.
141
What is systemic lupus erythematosus and what is it caused by? What is one of the classic symptoms?
\_\_\_\_\_\_\_\_\_\_\_ is an autoimmune disease caused when antibodies recognize snRNPs and sometime dsDNA as foreign invaders. An antinuclear antibody panel is often used to test for \_\_\_\_\_\_\_.
Classic symptom is a butterfly rash pattern on face.
142
What type of genus accounts for 95% of mushroom fatalities? What is the mechanism? What do patients usually die of?
Genus **Amanita**
Amanita phalloides= death cap mushroom
Alpha amanitinbind to RNA Polymerase II which prevents mRNA synthesis! No proteins no life! Patients will die of liver failure.
143
\_\_\_\_\_\_\_\_\_\_\_\_ occurs when there is an extremely high osmolality of the glomerular filtrate (using due to the presence of glucose, ketone bodies, or other solutes in colllecting duct) that cause water to be brought across the concentration gradient and to be excreted in urine. This will lead to extreme dehydration.
osmotic diuresis
144
1) Diabetic ketoacidosis 2) Heart Failure 3) Prolonged lack of oxygen (lactic acidosis)
What are 3 examples that can lead to a high anion gap? Why?Normal range of anion gap b/w 10-20mEq/L
145
carbonic anhydrase
What enzyme is responsible for the conversion of CO2 + H20 to H2CO3 (Carbonic acid)?
146
\_\_\_\_\_\_\_\_\_\_\_ is caused by a decrease in bicarbonate concentration and thus lowers the pH.
What is metabolic acidosis and what does it cause?
147
\_\_\_\_\_\_\_\_\_\_\_\_\_ is the accumulation of CO2 concentration in lungs/body which will decrease the pH. Can be caused by COPD, asthmapneumonia, and sleep apnea. (NOT BREATHING WELL)
What is respiratory acidosis and what can it be caused by?
148
Kussmaul respirations
What is the name of rapid breathing caused by diabetic ketoacidosis?
149
\_\_\_\_\_\_\_\_\_\_\_\_\_ is an X-linked dominant disease of the nuclear envelope that is caused by a mutation in the EMERIN (EMD) and the LAMININ (LMNA), which are both part of the nucleoskeleton membrane. These mutations disrupt the communication between the nucleus and the cytoplasm. This disease specifically affects STRIATED/INVOLUNTARY MUSCLES. Common symptoms are dilated cardiomyopathy, limb-girdle muscular dystrophy, stiff muscles, progressive muscle weakness and wasting. It also causes the walls of the heart to weaken and the chambers to enlarge; difficult to pump blood volume (leads to heart failure). Different from duchenne muscular dystrophy.
1) What is Emery-Dreifuss Muscular Dystrophy? 2)What type of genetic inheritance does it display? 3)What mutation is responsible for the disease? 4) What are symptoms of those affected with this disease? 5) What is a common organ that is affected?
150
\_\_\_\_\_\_\_\_\_ is a nuclear envelope disease caused by a mutation in the laminin A,C gene. Specifically, this disease prevents the organization of chromatin during mitosis (growing stage). Symptoms of childhood onset of premature aging, growth inhibition, baldness, osteoporosis, arthritis. Eventually most patients die of cardiovascular complications in teenage years.
1) What is Progeria? 2)What mutation is responsible for the disease? 3) What are symptoms of those affected with this disease? 4) What is a common organ that is affected to cause death?
151
\_\_\_\_\_\_\_\_\_\_ is a nuclear envelope disease caused by a mutation of laminin gene (A,C ZMPSTE24) which causes RIGED TRANSLUCENT SKIN, pulmonary hypoplasia (underdevelopment), impaired movements.
1) What is Restrictive Dermopathy? 2)What mutation is responsible for the disease? 3) What are symptoms of those affected with this disease?
152
The _______ is responsible for transcription of the genes for rRNA. The small and large subunits of the ribosomes are also completely translated in the \_\_\_\_\_\_, and then transported to the cytoplasm.
What is the role of the nucleolus.
153
peptidyl transferase (housed in 60S subunit)
What enzyme mediates the formation of peptide bonds in translation?
154
\_\_\_\_\_\_\_\_\_\_\_\_ recognize labeling sequences of specific proteins and shuttle these proteins to specific docking sites on the RER. Docked proteins are then sent through the pores INSIDE the RER where further modifications take place including glycosylation.
What are ribosome-associated-particles (RAP) and where are their jobs?
155
Alzheimer disease patients demonstrate this type of modification inside their neurons. Pathological changes in this structure have also been identified in Huntington's and Parkinson's disease.
Fragmented Golgi apparatus can be found in cells of what common disease?
156
This disease is caused an inability to catabolize branched-chain amino acids such as Leu, Ile, Val. (I Love Vermont) Since the enzyme ________ is missing to break down BCAAs, neurotoxicity buildup develops in bloodstream- untreated patient will suffer from mental retardation and high mortality rate. Treatment is to have diets that have low concentrations of BCAAs.
What is Maple Syrup Urine Disease
157
[branched-chain alpha-keto acid dehydrogenase] is the missing enzyme in this disease
What is the missing/deficient enzyme in Maple Syrup Urine Disease?
158
\_\_\_\_ is a disease caused by the inability of phenylalanine to be converted to tyrosine. thus phenylalanine buildup causes neurotoxicity and will lead to mental retardation if left untreated. Treatment for this disease is a diet that avoids phenylalanine.
What is PKU or phenylketonuria?
159
a multipass integral protein involved in transcytosis (for your neighbor)
What is caveolae?
160
\_\_\_\_\_\_ disease is caused by the congenital absence of the enzyme HEXOSAMINIDASE A (a lysosomal hydrolase). As a result way to much GM2 GANGLIOSIDE accumulates inside the lysosomes and causes symptoms such as 1) neurodegeneration 2) developmental delay 3) cherry red spot on macula 4) lysosomes with onion skin 5) DOES NOT EXHIBIT HEPATOSPLENOMEGALY(enlargement of liver and spleen)
What is Tay-Sachs Disease? What enzyme is it missing? What are the symptoms?
161
\_\_\_\_\_\_\_ is caused by the congenital absence of the enzyme SPHINGOMYELINASE (a type of lysosomal hydrolase). As a result sphingomyelin accumulates in lysosome. Can cause 1) Neurodegeneration 2)Foam cells (fat laden macrophages, indication of plaque buildup 3) Cherry-red spot on macula 4) hepatoslenoMEGALY
What is Nieman-Pick Disease? What enzyme is it missing? What are the symptoms?
162
\_\_\_\_\_\_\_ is caused by the congenital absence of the enzyme GLUCOCEREBROSIDASE (a type of lysosomal hydrolase) which prevents the breakdown of glucocerebroside in lysosome. This can cause 1)Pancytopenia (reduction in RBC, WBC and platelets) 2) Necrosis of the femur 3) bone crisis 4) \_\_\_\_\_\_\_cells 5) Lipid-laden macrophages 6) heptosplenoMEGALY
What is Gaucher Disease? What enzyme is it missing? What are the symptoms?
163
this is a peroxisomal disease caused by the absence of functional peroxisomes inside the cell. It is an autosomal recessive disorder that causes impaired neuronal migration and HYPOmyelination, which leads to progressive loss of hearing AND vision. Other symptoms include 1) cranial deformities 2)chondrodysplasia punctate 3) hypotonia (floppy baby syndrome) 4) seizures 5) apnea this disease usually causes death before 6 months old
Zellweger Syndrome (Cerebrohepatorenal syndrome)
164
a syndrome that has point mutations on genes that encode for mitochondrial oxidation proteins. This disease effects young males primarily and causes degeneration of retinal ganglion cells (optic nerve atrophy) eventually leading to loss of vision in both eyes (8 weeks separated), Mother is the carrier of this gene (MITOCHONDRIA)
What is Leber's Hereditary Optic Neuropathy
165
a syndrome that has point mutations on genes that encode for mitochondrial oxidation proteins. Symptoms include myoclonus (involuntary jerking of muscles), seizures, dementia, optic atrophy, neuropathy, arrhythmias. Usually multiple symptoms present at the same time. Mother is the carrier of this gene (MITOCHONDRIA)
Myoclonic Epilepsy w/ Ragged Red Fibers
166
a disorder caused by the replacement of glycine by another more bulky amino acid in the formation of cartilage (and ultimately bone). Symptoms include blue (translucent) sclera, hearing loss due to funky middle ear bones, dental imperfections. -type I can often be mistaken for child abuse -type 2 cause prenatal death
osteogenesis imperfect
167
\_\_\_\_\_\_\_\_\_\_\_ is a blood disorder caused by a mutation on RBC that changes GLUTAMATE to VALINE. That changes to lifespan of the RBC from 120 days to ~20 days. Symptoms include episodes of pain (due to anoxia in capillaries) , chronic hemolytic anemia, and hyperbilirubinemia. Infected RBCs will also not travel as far on electrophoresis due to loss of negative charge from glutamate.
What is sickle cell anemia?
168
this toxin blocks the voltage gated Na+ channels and prevents them from working. Without these voltage gated sodium channels, muscles contration is impossible, so it leads to paralysis. IT IS A SALT WATER FISH. IRONIC?
What effect does Fugu fish toxin (puffer fish) have on the cell and what symptoms does it cause?
169
This enzyme relieves the supercoiling of DNA caused by helicase by making a nick on one strand. Involved in both the cutting and the reanealing of DNA.
What is the job of topoisomerase I?
170
This disease is the result in the **mutation or absense of the LDL receptor** on the surface of the cell membrane. The LDL receptor is involved with the absorption and destuction of LDL. This mutation/absense causes excessive build of LDL which leads to **HIGH cholesterol levels**.
Symptoms include
* **xanthomas** (lipid deposits on skin)
* **heterozygous** inheritance will lead to MI in _adolescence_
* **homozygous** inheritance will lead to MI in _childhood_
What is familial hypercholesterolemia? What causes it? What are the symptoms? What is the difference between recieving a homozygous and heterozygous copy of the genetic disorder?
171
A ______ is a type of mebrane protein that utilizes the concentration gradient formed by the Na+/K+ pump to serve it's purpose of sneaking a desired compound into the cell along with an ion flowing down it's concentration gradient. Both substances entering the cell require the **binding of a carrier protein**. For the reason a _________ it consider an example of **secondary active transport**. An example of this is **glucose/AA/Na+**
What is a symport/cotransport? It it a passive or active transport? Give an example of a symport/co-transport.
172
This disease follows a *autosomal recessive inheritance* (mutuation on ATP7B gene causes defect of _copper-dependent ATP-ase_) cells **can not secrete copper out of cells,** symptoms are caused by excessive buildup of copper (CNS, kidneys, eyes, liver). Classified as a cell membrane disease.
happens in active hepatitis, liver fibrosis, and cirrhosis
_Symptoms_
* tremors
* muscle stiffness
* personality changes
* anxiety
* hallucinations
hint: (volleyball cannot get copper out of it)
What is Wilson's Disease? What type of disease is it classified as? What causes it/gene affected? What are the symptoms? What is its genetic inheritance?
173
\_\_\_\_\_\_\_\_\_ results in the drying out of many bodily organs/secretions. It results from the mutation of the **CFTR gene** and is **autosomal recessive**. A mutation in the CFTR gene leads to _defect in the Cl- membrane channel_ (CFTR protein.)
**Symptoms** include
* production of abnormally think secretions in the GI, pulmonary system
* salty-tasting skin
* difficulty breathing, coughing up mucus, pulmonary infections
* pancreative, liver, and renal insufficiency
* infertility in males
LOTS or ALL of these symptoms are caused because Cl- stays OUTSIDE of the cell due to broken membrane channel and pulls out its friend Na+. Water always follows (NaCl) and therefore you get many dehydrated products (alveoli, sprerm, etc)
What is Cystic fibrosis? What type of disease is it classified as? What causes it/gene affected? What are the symptoms? What is its genetic inheritance?
174
DNA Polymerase III
Two high energy bonds are needed for each nucleotide that is added.
DNA Pol. III has proofreading ability, and if a mistake is made, 3'--\>5' exonuclease activity
Which enzymes is responsible for elongating the leading and lagging strand in prokaryotic DNA? How much energy is required per nucleotide? How does it maintain accuracy? What is the response if a mistake is made in DNA synthesis?
175
DNA Polymerase I
It has exonuclease activity in BOTH directions. Replaces rNTP with dNTP. Still has not completely sealed DNA.
(DNA Pol. I holds up 1 finger annoyingly to remind there is work left to be done, bc RNA primers are still present in DNA)
Which enzyme is responsible for going back and removing all of the RNA primers that were used in the formation of Okazaki fragments?
176
DNA ligase
Which enzyme fills in the nick in the DNA after RNA primer has been replaced by correct dNTP by DNA Pol. I?
177
After DNA has been replicated certain proteins are able to scan the DNA for incorrect coding (mismatches in base pairing) and use endonuclease to nick the damaged strand and remove incorrect region.
What is mismatch repair?
178
a defect in mismatch repair does not allow for editing of newly synthesized DNA, which leads to an increase in mistakes. This causes cancer because replication can no longer be controlled.
-autosomal DOMINANT inheritance
Lynch= use colorectal to tie this :(
What is Lynch Syndrome (hereditary nonpolyposis colorectal cancer, HNPCC)
179
1. TATA BOX (PRIBNOW BOX)
* -10 on coding strand before start of transcription at +1
* * -35 SEQUENCE
What are the two most famous PROMOTER sequences used for start of transcription?
180
\_\_\_\_\_\_\_\_ is a type of antibiotic that bind to RNA polymerase and prevent transcription initiation (probably by inhibiting action of sigma factor). It is know to treat tuberculosis.
RIPS off DNA. Think rope/lasso/tube (rho independent)
What is the action of Rifampin (rifamycin)? What disease does it treat?
181
\_\_\_\_\_\_\_\_\_\_\_ is an autoimmune disease caused when antibodies recognize snRNPs and sometime dsDNA as foreign invaders. An antinuclear antibody panel is often used to test for \_\_\_\_\_\_\_.
Classic symptom is a butterfly rash pattern on face.
What is systemic lupus erythematosus and what is it caused by? What is one of the classic symptoms?
182
Genus **Amanita**
Amanita phalloides= death cap mushroom
Alpha amanitinbind to RNA Polymerase II which prevents mRNA synthesis! No proteins no life! Patients will die of liver failure.
What type of genus accounts for 95% of mushroom fatalities? What is the mechanism? What do patients usually die of?
183
What are the two general classifications of genes in eukaryotic gene expressions?
1) Housekeeping genes- always expressed and not regulated. Needed for life on a daily basis
2) Regulated genes- required only under certain conditions (i.e. lactose metabolism)
184
What is the lac operon actively transcribed? What are the conditions?
The lac operon in e. coli is only actively transcribed when there is
1) a lack of glucose present
2) a presence of lactose
any other circumstances the lac operon will remain off
185
What is the name of the lac operon repressor gene that constitutively transcribed (a housekeeping gene)? What is it's role?
Lac I is the ______ gene the is constitutively expressed.
Lac I transcribed for a RNA strand that actively binds to the operator region and prevents transcription of lactose metabolism genes.
186
On a transcriptional mechanism level, what are the two requirements necessary in order for the transcription of lactose metabolism genes to take place?
1) ADDITION of cAMP/CAP structure to the CAP binding site (located directly upstream of the promoter region (TATA box, -35 etc). This serve to SHOVE THE RNA Polymerase forward
2) the REMOVAL of the LacI transcription from the operator.
187
What does CAP stand for in regards to the lac operon?
Catabolite gene Activator Protein
188
How does glucose's presence/absence mechanistically effect the activation of the lac operon? What additional enzymes are associated with this process?
If glucose is present in high concentration then the membrane bound enzyme ADENLYL CYCLASE will NOT use ATP to produce cAMP.
If glucose is not in high concentration then ADENYlY CYCLASE will use intracellular ATP to produce cAMP.
cAMP will join with CAP to bind to CAP binding site and attempt to shove RNA Polymerase forward.
189
In order for lac operon to function, how is the transcript of the repressor protein (LacI) removed from the operator?
When lactose is present in high concentration the a small amount of allolactose will be produced.
Allolactose will bind to LacI transcript causing a conformational change in structure, and will therefore remove in from the operator.
190
What is the default setting for eukaryotic gene expression?
Are eukaryotic repressor genes common?
Off, because DNA is highly condensed in chromatin which makes it very inaccesible.
eukaryotic repressor genes are NOT common
191
What are the functions of enhancers and what are some unique features?
Enhancers are regions of DNA upstream OR downstream of intended transcription site that promote transcription of the particular gene.
They are also called cis-acting regulatory elements
These DNA sequences are able to be brought close to gene through bending of the DNA molecule.
192
What are the two components of eukaryotic transcription factors?
1) DNA binding domain (rich with lys and arg)
2) Activation domain- binds with other TF and RNA Pol. II to stabilize molecule for transcription. They also can recruit chromatin modifying proteins (such as acetylases) which will help make the DNA more/less accessible.
193
What enzyme is the rate limiting step in gluconeogenesis? What two hormones regulate this enzyme?
PEPCK= phosphoenolpyruvate caboxykinase
regulated by
1) glucagon (hypoglycemia)
2) cortisol (stress, starvation)
194
What are some of the unique features of glucagon and how is it used to help regulate gluconeogenesis? Know how to draw this entire pathway.
Glucagon is a hydrophilic (water soluble) hormone. This means that is must use a membrane bound receptor.
1) Glucagon binds to adenlyl cylcase, which converts ATP--\> cAMP.
2) cAMP activation protein kinase A
3) protein kinase A phosphorylates and ACTIVES CREB. CREB is a transcription factor (cAMP Response Element Binding protein)
4) CREB then enters nucleus and binds to CRE (enhancer region, cAMP response Element)
5) CRE (enhancer region) induces transcription of genes that encode for PEPCK (phosphoenolpyruvate caboxykinase)
6) PEPCK is used to increase Gluconeogenesis.
195
What are some of the unique features of cortisol and how is it used to help regulate gluconeogenesis? Know how to draw this entire pathway.
Cortisol is a hydrophobic hormones (lipid soluble) that can actively cross cell membrane without receptor protein.
1) cortisol crosses cell membrane and binds to intracellular receptor
2) cortisol-receptor complex goes through the nuclues and binds to GRE (glucocorticoid response element) which is a enhancer region.
3) GRE induces production of PEPCK.
4) PEPCK increases gluconeogenesis
196
What type of cell are responsible for creating the PEPCK enzyme for gluconeogenesis?
heptocyte (liver cell)
197
What are some of the general techniques employeed by RNAi to prevent certain genes from being expressed?
Reduction of translated:
1) RNAi will be complemetary to the mRNA gene they are trying to limit. Formation of dsRNA occurs and ribosomes cannot read dsRNA.
2) RNAi will be complemetary to the mRNA gene they are trying to limit. Formation of dsRNA occurs and this SIGNALS CELL to destroy dsRNA, because often viruses use dsRNA.
198
What is a RISC? What does it do?
RNA Induced Silencing Complex. (a type of protein)
RISC combines with miRNA to target specific mRNA to silence or destroy.
199
What is siRNA?
a stands of RNA that is scientifically designed to block translation of specific genes.
mimicks intracellular miRNA
200
What are chylomicrons?
lipoprotein particles that consist of triglycerides, phospholipids, cholesterol, and proteins. They transport dietary lipids from the intestines to other locations in the body.
201
How does the Apo B gene undergo posttranscriptional modification?
Apo B-100 is a liver gene that is used to transcribe for VLDL
Apo B-48 is a segmented portion of the same gene that is used in the intestines to create chylomicrons.
Post transcriptions modification occurs to change CAA--\> UAA around the 48th AA. UAA is a stop codon.
202
What does methylation of DNA usually do? What do acetylation of DNA usually do?
methylation= deactivates DNA, make chromatin more dense
acetylation= activates DNA, make is less dense
203
In terms of respiration pathways, anemia and excessive bleeding can both cause \_\_\_\_\_\_\_\_\_\_\_\_\_\_; which will lead to feeling _______ and \_\_\_\_\_\_\_\_.
deficiency in O2; lethargy and fatigue
204
Describe the composition of a hemoglobin molecule.
Hemoglobin is composed of 4 subunits (each subunits contains 8 alpha-helices) and is considered to have a quaternary structure.
Hemoglobin has a total of 4 heme sites.
In adults; hemoglobin is composed of 2alpha subunits +2 beta subunits= 4 subunits
alpha and beta subunits are linked by STRONG hydrophobic interactions
205
Describe the composition of myoglobin.
Myoglobin is a SINGULAR protein (tertiary structure) that only has unit subunit (8 alpha helices).
Myoglobin has 1 heme site.
206
What is in the center of the porphyrin ring structure used in the heme group for both myoglobin and hemaglobin?
Fe2+.
Oxygen will NOT bind to Fe3+
207
What type of amino acids surround the heme group (both proximally and distally) to partially negative the negative charge of the binding oxygen?
A distal (His 64)and proximal (His 93) histidine
208
What is Kd?
Dissociation constant. A term that measures the substrate concentration at 50% binding/dissociation
209
Compare the affinities for oxygen between
1) fetal hemoglobin
2) myoglobin
3) adult hemoglobin
Myoglobin (Mb) has the STRONGEST affinity for O2.
Fetal hemoglobin (HbF) has a STRONG affinity for 02
Adult hemoglobin (HbA)has the WEAKEST affinity for O2
210
Hemoglobin undergoes this type of binding. How does structure and binding type of hemoglobin affect it Kd curve?
Hemoglobin udergoes cooperative binding. This means that the affinity for oxygen increases with each addition oxygen that is added to the molecule. 1st O2 is by far the hardest to add.
Cooperative binding leads to a sigmoidal hemoglobin Kd curve.
211
What is the shape of a myoglobin Kd curve?
Hyperbolic
212
Hemoglobin is in a _____ state when it is fully unstaturated of oxygens in the muscles(deoxyhemoglobin).
Hemoglobin is in a _______ state when it is fully saturated with oxygen in the lungs.
tense (T state)
relaxed (R state)
213
Describe the Bohr effect in term of hemoglobin affinity.
The bohr effective states that when the physiological pH is decreased then hemoglobins affinity for oxygen will also decease. This shifts Kd to the right.
low pH/High [H+] stabilizes the T (deoxy) form
High pH/Low [H+] favors the R (oxy) form
this is helpful for oxygen unloading bc pH is lower in the muscles! yay!
214
What 2,3 bisphosphoglycerate (2,3 BPG)? How is it relevent in terms of oxygen delivery? How does in change the Kd curve?
2,3 BPG is a substrate produce is glycolysis (anaerobic fermentation!) that is an **NEGATIVE allosteric regulator of Hb**. Increased concentration of 2,3 BPG makes oxygen easier to upload off of Hb (**decreases Hb affinity for O2**).
Many people go to high altitude to train for endurance sports because you will increase you concentration of 2,3 BPG so that oxygen unloading into muscle cells become even more efficient. (**pushes Kd curve to the right**)
215
What are three ways to increase the 2,3 BPG concentration in the RBC?
How can you decrease the 2,3 BPG concentration?
1) High altitudes
2) Chronic hypoxia (COPD)
3) Chronic anemia
decrease concentration from blood storage
216
What is methemoglobin? What are the symptoms?How do you get rid of it?
An oxidized form of hemoglobin that has Fe3+ at the center of the heme binding substrate. Won't bind to O2 but has a high affinity for cyanide. Can be caused by smoking etc.
Will turn skin and mucous membrane brownish blue, and blood a chocolate color
Can be reversed to form Fe2+ with antioxidants (vitamin C) and methylene blue.
217
How can carbon monoxide kill you? What is the name of the compound it forms when it kills you?
Carbon monoxide binds to heme group on hemoglobin 200x stronger than oxygen, therefore it outcompetes oxygen for binding site and you die from suffocation.
Carboxyhemoglobin
218
What is unique about HbF and what properties does it give the hemoglobin?
HbF has the beta subunits replaced with gamma subunits.
The gamma subunit of HbF do not bind as strongly with 2,3 BPG (competitive inhibitor), therefore it gives the HbF a STRONGER affinity for oxygen. This allows the baby to recieve oxygen from mother across the placenta.
Usually HbF is replaced for HbA1 or HbA2 with 6-9 months of birth. Persistent HbF can help protect against sickle cell anemia
219
What is HbA1C? What is it used for?
Heboglobin A1C is a glycosylation of the Hb that happens in a slow, non-enzymatic reaction. The extent of glycosylation is dependent on the concentration of glucose in the body.
A high HbA1C indicates uncontrolled diabetes.
220
What causes the change of shape for RBC with HbS?
Sickle Cell Anemia
glutamate (-) ---\> valine
at low concentration of o2 valine start to form hydrophobic interactions with AA on other side of RBC causing cell to sickle
221
What is alpha-thalassemia?
First of all you, have 4 alpha alleles that code for the TWO alpha subunits.
alpha-thalassemia causes gene deletions of alleles that code for alpha subunit.
Varying degree of mutations are caused by more allele deletions.
4 allele deletion: No α-globin. Excess γ-globin forms γ4 **_(Hb Barts)._** Incompatible with life (causes ***hydrops fetalis***).
3 allele deletion: inheritance of chromosome with cis deletion + a chromosome with 1 allele deleted HbH disease. Very little α-globin. Excess β-globin forms β4 (HbH).
2 allele deletion: less clinically severe anemia.
1 allele deletion: no anemia (clinically silent).
222
What is beta-thalassemia?
point mutations in splice sites and promoter sequences that downgrade hemoglobin beta subunit production.
heterozygote : beta-thalassemia minor- beta chain is underproduced but is usally is asymptomatic
homozygote: beta-thalassemia major- beta chain is ABSENT. ***Requires blood transfusions.*** Cause severe microcytic, anisopoikilcytosis (abnormally shaped RBC). Also can cause skeletal deformities.
223
What are the 4 classes of cytoskeleton protein?
Microtubules
Intermediate Filaments
Accessory Proteins
Actin filaments (microfilaments)
224
What is the definition of shapers? What are the polymer molecules made of proteins?
Shapes are protein filaments that support the shape of the cell; provide rigidity
1) Microtubules (25nm)
2) Intermediate Filaments (10 nm)
3) Actin Filaments (microfilaments) (8nm)
225
What are the Movers of the cell? List the three classes.
Movers are motor proteins that enable movement of cargo carrying vesicles, which are powered by the breakdown of ATP.
1) Kinesin
2) Dynein
3) Myosin
Kevin Middle-Name Durant
226
Describe the assembly of microtubules?
2 heterodimers (alpha and beta)
Come together in long chains to form protofilaments
Form tubule using many protofilaments
227
What is the function of microtubules?
enable chromosome movement during mitosis/meisosis
228
***_Folate_***
1) what is its function
2) symptoms of folate deficiency?
3) does excessive amounts cause toxicity?
4) MCC of deficiency? (2)
5) daily recommended doses
6) role of methotrexate (know briefly)
7) diseases caused by deficiency
Folate (THF) is used as a precursor in nucleotide and amino acid synthesis. It is one of the vitamins that has the most common deficiencies.
The major cause of folate deficiency is due to alcoholism (poor nutrition and absorption) and pregnant mothers, who must also provide EXTRA nucleotides for growing babies.
Symptoms of the folate deficiency include megoblastic anemia (macrocytic anemia) (RBC that are LARGE and incapable of completing final steps in cell division due to lack of nucleotides) and increased concentrations of homocystein (can bind with LDL to cause plaque buildup).
Methotrexate inhibits precursor enzyme to THF, which prevents ongiong synthesis of nucleotides.
It is recommended for the average adult to consume 0.1mg of folate/day. Childbearing women are recommended to consume 0.4mg of folate/day. High doses of THF have shown to significantly reduce the risk for neural tube defects (spinobifida or anencephaly)
Vitamin B12 plays are large role in determining whether folate is convert for N5 methylfolate to USABLE version (THF)
229
Vitamin B12 (cobalamin)
## Footnote
1) functions (2)
2) symptoms of deficiency
3) excess toxic?
4) MCC of deficiency
5) absorption mechanism?
Vitamin B12 only is involved in two critical pathways.
1) Used as an enzyme to **convert homocysteine to methionine** (gets help for N5methylTHF)
2) used in the **catabolism of proteins and fatty acids with an odd number of carbons**
Deficiency in B12 can lead to excessive buildup of homocystein and lack of function THF (bc THF is stuck in N5methylTHF form) Homocystein is known to cause **heart disease from plaque buildup.** This cooperative friendship of B12 and THF also causes a deficiency of B12 to **cause megoblastic anemia due to insufficient amounts of folate** (folate trap hypothesis)**.** Deficiency in B12 can also cause **neuropathy** because of excessive accumulation of odd number FA in neuron which inhibit signal propagation.
B12 is almost exclusively synthesized by microorganisms therefore hard to get excessive amounts.
Infants often don't have enough B12 due to lack of flora in gut. Can also get B12 through eating meat, fish
B12 has a complication absorption as it is ushered by multiple carrier proteins throughout the body
1) **R-protein** (a salivary glycoprotein)
2) **IF** (intrinsic factor- binds in gut and help B12 cross plasma membranes)
230
Vitamin C (ascorbic acid)
## Footnote
1) function
2) symptoms of deficiency
3) excess toxic?
4) MCC of deficiency
Vitamin C (ascorbic acid) is a water soluble vitamin and acts as a reducing agent (gives electrons) in many reactions.
Vitamin C deficiency is also interconnected with scurvy **(collagen disease)** because Vit C is needed for the hydroxylation of lysyl and prolyl, **Scurvy** cause easy bleeding, easy bruising, gum disease, poor wound healing.
Vitamin C deficiency is also cause of **MICROTIC ANEMIA.**
Vit. C concentration is also **_needed for iron absorption_** in the gut.
Not toxic is excessive amount (pee is out)
MCC is ascorbic acid deficiency is not eating enough fruits or vegetables.
231
VItamin B6 (pyrid--)
## Footnote
1) function
2) symptoms of deficiency
3) excess toxic?
4) MCC of deficiency (2)
NEED MEMORY CUE
In order to "fly like a B6" you must have power heme protein, and help with proteinsynthesis.
however whe you "fly so high" you can also FALL down, therfore B6 on water-soluble vitamin you can overdose on.
Vitamin B6 in involved in metabolism of amino acids, heme synthesis, and nitrogen metabolism.
Deficiency is RARE because found in many foods.However isoniazid therapy (for TB) can cause B6 deficiency.
Excessive amounts of B6 (only supplemental levels) can cause peripheral neuropathy, severe sensory neuropathy (can't walk straight after getting off plane) and sideroblastic anemia.
232
Thiamine (B1)
## Footnote
1) function
2) symptoms of deficiency
4) MCC of deficiency
5) What diseases are caused by a deficiency?
Thiamine (TPP= thiamine pyrophospate is active version) is a vitamin that is water soluble and is used in alot of **energy producing pathways** (used as a cosubstrate TWICE in krebs cylce)
1) pyruvate dehydrogenase
2) aphla ketoglutarate dehydrogenase
also used in 3)brainched chain alpha keto acid dehydrogenase (Maple Syrup Urine Disease)
4) transketolase (diagnostic test)
Diseases: **beriberi**- caused by not enough thiamine (B1) caused by eating only rice.
dry- peripheral neuropathy; wet-cardiac dysfunction with edema
**Wernicke-Korsakoff syndrome:** causes ataxia, confusion and can progress to memory loss, psychosis.
233
Niacin (B3)
## Footnote
1) function
2) symptoms of deficiency
3) excess toxic?
4) MCC of deficiency
Memory trick: Niacin(B3) Niacin taste in corn
Niacin (B3 is an enzyme that is used to make NAD+--\> NADP+.
**Corn is low in niacin and tryophan** so diets that include lots of corn can result in a deficiency.
Niacin flushing of face and **_pellegra (4D)_**.
-death, demensia, diarrhea, dermatitis
**_Hartnup disease_** (poor trytophan absorption) can mimic pellegra
234
Riboflavin (B2)
## Footnote
What is it used to make?
Riboflavin (b2) is used to make active coenzyme FAD
235
Biotin
## Footnote
1) function
2) symptoms of deficiency
Used for ketin strength (nail and hair). Flora has role in creation. Binds strongly with avidin.
236
Pantothenic Acid (B5)
## Footnote
1)function
component of conenzyme A (carries acyl compounds)
widley distributed in food,deficiency not common
237
•Compare and contrast the nutritional anemias in terms of classification, causes, and differentiation
**Microcytic anemia (MCV\<80):** caused by vitamin C deficiency, iron deficiency, B6 deficiency
**Macrocytic anemia (MCV\>100):** caused by deficiency in B12 and folate
238
•Identify the recommended dietary intake of folate for an average individual and a women of childbearing potential
It is recommended for the average adult to consume 0.1mg of folate/day. Childbearing women are recommended to consume 0.4mg of folate/day. High doses of THF have shown to significantly reduce the risk for neural tube defects (spinobifida or anencephaly)
239
•Describe the process for uptake of vitamin B12
B12 linked to R-protein (salivary glycoprotein) in mouth, stays attached through stomach,drops off in intestines
B12 picked up by IF- helps ushes B12 through cell membranes
240
•Explain what is meant by pernicious anemia and the underlying cause
Pernicious anemia is the severe lack of IF and therefore B12 cannot be shuttled into cells, which also prevents folate from being used in nucleotide synthesis
241
•Explain how a deficiency of vitamin C causes the symptoms of scurvy
vit c used from hydroxylation of prolyl and lysyl of collagen residues. collagen does not form correctly
242
•Describe how a thiamine deficiency can be diagnosed in terms of symptoms and diagnostic tests
symptoms: low energy
beriberi
wernicke (ataxia, confusion)-karsakoff (slurred speach, psychosis)
diagnostic test
low thiamine can be found out through diagnostic testing of enzyme transketolase (present in RBCs)
RBC also associated with energy
243
•Describe the relationship between niacin (B3)and tryptophan
both can be used for the conversion of NAD+ to NADP+
244
# Define (and contrast) the following terms:
• Strict vs. opportunistic pathogens
**_Strict_** pathogens are always pathogenic and are not native to the organism.
**_Opportunistic pathogens_** are usually part of your normal flora or encountered in your everyday life BUT, when they can opportunity to spread somewhere they usually dont habitate, they take it!
245
