MCB II Block 3

Disclaimer: Topics from Block 3 not covered on this page include: Hexose Monophosphate Pathway, Disaccharides, Fatty Acid Oxidation, Fatty Acid Synthesis, Ketones, Eicosanoids, Phospholipids and Glycolipids.

  1. GAGS & Glycoproteins
  2. Cholesterol Synthesis
  3. Steroid Hormones
  4. Biotechnology
  5. Birth Defects
  6. Blood Clotting


Q: What are GAGs
A: GAGs are repeated, unbranched dimers of acidic (Glucuronic or Iduronic acid) and amino sugars (Glucosamine)

Q: What explains GAGs’ lubricant qualities?
A: negative charges

Q: What is the only GAG not covalently connected to a core protein?
A: hyaluronic acid. It is connected to proteoglycan via ionic bond.

Q: How does the GAG connect to the core protein?
A: GAG connects to Linkage Region (Xylose/Galactose), which connects to Serine side chain, which connects with Core Protein.

Q: Hyaluronic acid connect to proteoglycan (unique in that connect via ionic bond). What are some examples of proteoglycans?
A: chondroitin sulfate, heparin dermatan sulfate, and keratan sulfate.

Q: How do you make the amino sugar (Glucosamine) in GAG?
A: Combine F6P and Glutamine to form Glucosamine-6-P and Glutamate. Glucosamine-6-P can then be used to make NANA, GlcNAc, and GalNAc ;

Q: How do you make the acidic sugar in GAG?
A:Glucose-1-P + UTP → UDP-Glucose → UDP-Glucuronic Acid via Uronic Pathway

Q: How do you make the full deal GAG?
A: UDP-Xylose + Core Protein via xylosyl-transferase → core protein-Xylose + UDP. Then add 2 galactose. Add amino and acidic sugars in alternating order. Finally, add SO4 from PAPS. Notice that Xylose is the first one to be added to the core protein.

Q: Remember PAPS transfers sulfate to end of GAG. How are PAPS made?
A: SO4 + ATP → adenosine-5’-phosphosulfate. Add another ATP to this and get PAPS. So as you can see, you spend 3 ATPs and it has an SO4.

Q: What will happen if you fail to sulfate your GAG by PAPS on the last step?
A: You develop chondrodystrophies aka “defects in skeletal development”

Q: How do you degrade GAG?
A: First phagocytize it then digest in lysosome.

Q: What group of diseases happen because GAG fail to degrade?
A: mucopolysaccharidoses – Hurler, Sanfilippo, Hunter, and Sly Syndromes.

Q: What is deficient in Hurler’s Syndrome?
A: a-L-iduronidase

Q: What is deficient in Hunter’s Syndrome?
A: Iduronate sulfatase

Q: What is deficient in Sly’s Syndrome?
A: β-glucuronidase – can’t degrade dermatan sulfate and heparan sulfate.

Q: What is deficient in Sanfilippo’s Syndrome?
A: 4 enzymes that remove N-sulfated or acetylated glucosamines from heparan sulfate.

Q: In Glycoproteins, how are proteins and oligosaccharides attached?
A: Covalently.

Q: What kind of molecule is all of our secreted globular proteins?
A: glycoproteins.

Q: In glycoproteins, the link between the D-hexose sugar and the protein can be N-linked or O-linked. What amino acid is used in each one?
A: N-linked connect via amino of Asparagine. O-linked connect via hydroxyl of Serine or Threonine.

Q: How are A and B antigens formed from O antigens in blood?
A: O + GalNAc = A. O + Gal = B. So A is the most complex one… has an extra galactose and an N-acetate.

Q: What is the only O-linked glycoproteins that does not connect via serine/threonine?
A: Collagen – connect via OH group of hydroxylysine. Need Vitamin C to form hydroxylysine.

Q: What are two classes of N-linked oligosaccharides of glycoproteins?
A: high mannose content and complex oligosaccharide. They both have a core pentasaccharide, but depart from there.

Q: Where are the Glycoproteins made?
A: in the Rough ER, even when it is a cytosolic protein

Q: How are oligosaccharides transferred to proteins in glycoproteins?
A: via dolichol in the ER lumen and Golgi.

Q: Where are the destinations of glycoproteins?
A: lysosome or cytoplasm

Q: What does the glycoprotein need in order to go to lysosome?
A: mannose-6-P residue (added in Golgi), which is recycled after it transfers the glycoprotein to lysosome.

Q: What inability causes I-cell disease?
A: Inability to phosphorylate mannose residues to tag glycoproteins to go to lysosome. Can’t become lysosomal hydrolases – can’t breakdown stuff.

Q: What are features of I-cell disease?
A: “course features,” Alveolar ridges, Gum hypertrophy, MR, death by 8 yrs.


Q: Describe structure of cholesterol.
A: 4 rings. 2 methyl groups, 1 OH group.

Q: What is cholesterol absorption dependent on?
A: Bile salts (converted from cholesterol) and dietary intake.

Q: Do bacteria and plants produce cholesterol?
A: No

Q: What is the raw material for cholesterol synthesis?
A: Acetyl CoA

Q: Where is cholesterol synthesized?
A: In the cytosol. BUT remember acetyl CoA is made in the mitochondria, so must be shuttled out via citrate!

Q: What is the first step in making cholesterol from 2 acetyl CoAs?
A: first, HMG-CoA synthase turns the two acetyl CoAs into HMG CoA

Q: What is the first commited step in cholesterol synthesis?
A: HMG CoA reductase turns HMG CoA into Mevalonic Acid. Requires 2 NADPH, releases CoA.

Q: Describe the five steps after Mevalonate.
A: Mevalonate (6 C’s) → isopentenyl PP (5 C’s) → dimethylallyl PP (5 C’s) → combine 6 of these to form Squalene (30 C’s) → cyclized to Lanosterol (30 C’s)

Q: What is the first sterol product during cholesterol synthesis?
A: Lanosterol.

Q: How many carbons are in cholesterol?
A: 27

Q: How does cholesterol do feedback inhibition on HMG CoA reductase?
A: at the transcriptional and post-transcriptional levels of HMG-CoA Reductase synthesis.

Q: Is phosphorylated HMG CoA reductase the active or inactive form?
A: inactive.

Q: Why does insulin stimulate HMG CoA reductase production?
A: because insulin has lipogenic effects, it provides enough energy to pay for the making of HMG-CoA reductase.

Q: How does Lovastatin, Simvastatin, and Mevastatin treat hypercholesterolemic patients?
A: by competing with normal HMG to bind to the active site of HMG-CoA reductase, thus inhibiting HMG-CoA reductase and cholesterol synthesis.

Q: Isopentenyl PP and dimethylallyl PP in our five-step cholesterol synthesis are the ingredients to make what?
A: isoprenoids, like ubiquinone, dolichol, farnesyl/geranyl groups (membrane-protein anchors)

Q: How is isopentenyl PP and dimethylallyl PP used to make Geranyl PP and Farnesyl PP?
A: combine the two to make geranyl. Add another Isopentenyl PP to make Farnesyl PP.

Q: What is the role of farnesyl PP?
A: Farnesyl anchors proteins into membranes. Farnesyl is transferred to protein via farnesyl transferase, taking off the PP.

Q: Why is farnesyl transferase a good target for cancer drugs?
A: because if you can’t make protein anchors, cancer cells can’t anchor to each other.

Q: Which vitamins are isoprenoids?
A: ADEK (all fat-soluble vitamins).

Q: What isoprenoid accumulates in patients with Refsum’s disease?
A: phytanic acid.

Q:Since you can’t degrade steroids/cholesterol, how do you get rid of them?
A: convert them into soluble bile acids, but costly, so retain them as long as possible. There’s a limit on how much cholesterol can be eliminated per day.

Q: What is the first step in turning cholesterol into bile salt?
A: Cholesterol → Cholic acid via Cholesterol-7-a-hydroxylase (so adds OH to 7 C in cholesterol)

Q: What are the feedback mechanisms of Cholesterol-7-a-hydroxylase?
A: Cholic acid inhibits it, cholesterol promotes it.

Q: What is special about the structure of bile salt?
A: It is ionized on one side, which allows it to form micelle with triglycerides, and associate with pancreatic lipase.

Q: Why is cholesterol important in our diet?
A: Because it is used to make bile salts, which is used to emulsify fats, to aid in its digestion.

Q: Name two major bile salts.
A: glycocholic acid (Glycine + Cholic Acid CoA). Taurochenodeoxycholic acid (Taurine + Chenodeoxycholic acid CoA)

Q: Taurine has a special charged group on it.. What is it?
A: SO4

Q: How does dietary cholesterol affect HMG-CoA Reductase and 7-a-hydroxylase?
A: It inhibits HMG-CoA reductase but induces 7-a-hydroxylase… make sures if you eat cholesterol, your body won’t be making it, and your body will be turning the cholesterol you ate into bile salts.

Q: How is taurine made from methionine and cysteine?
A: combine the SO4 from methionine with cysteine (3 C) via cysteine sulfinate decarboxylase, which also cleaves off a C.

Q: Most of the bile salts in your body are recycled. Between what two organs do they circulate?
A: liver and intestines. Enterohepatic circulation.

Q: What are gallstones made of?
A: cholesterol from bile salt/ micelles (never just cholesterol alone).

Q: What is Cholestasis?
A: When gall stones block the bile duct. It leads to jaundice.

Q: Why can’t gallstones be picked up by X-rays?
A: because they are not calcified.

Q: How do you treat cholelithiasis?
A: cut out gall bladder with cholecystectomy (remember just used for storage of bile, so bile will still be produced and released, but maybe at abnormal times.)


Q: What structure do all steroid hormones have in common?
A: OH group at C3

Q: What structure do all mineralocorticoids have in common?
A: aldehyde group at C18

Q: What structure do all estrogens have in common?
A: ring A is aromatic.

Q: What does desmolase do?
A: cleaves side chain of cholesterol to make pregnenolone, which is a precursor to many hormones, like progesterone.

Q: What are the steps in making Estrogen?
A: Cholesterol → Pregnenolone → Progesterone → 17-a-hydroxyprogesterone → testosterone → Estradiol (aromatize ring A)

Q: What are the steps in making Aldosterone?
A: Cholesterol → Pregnenolone → Progesterone → 11-Deoxycorticosterone → Corticosterone → Aldosterone.

Q: What are the steps in making Cortisol?
A: Cholesterol → Pregnenolone → Progesterone → 17-a-hydroxyprogesterone → 11-Deoxycortisol → Cortisol.

Q: What enzyme catalyzes Cholesterol → Pregnenolone?
A: Desmolase

Q: What enzyme catalyzes Pregnenolone → Progesterone?
A: 3-b-hydroxysteroid DeH

Q: What enzyme catalyzes Progesterone → 17-a-hydroxyprogesterone?
A: 17-a-hydroxylase

Q: What enzyme catalyses Progesterone → 11-Deoxycorticosterone, and 17-a-hydroxyprogesterone → 11-Deoxycortisol?
A: 21-a-hydroxylase

Q: What enzyme catalyses 11-deoxycorticosterone → Corticosterone, and 11-deoxycortisol → cortisol?
A: 11-b-hydroxylase

Q What else can you make with Progesterone?
A: aldosterone and cortisol.

Q: What is the active type of testosterone called?
A: Dihydrotestosterone (DHT)

Q: Where are estrogens produced in males?
A: adipose tissue, liver, skin, brain.

Q: What enzymes causes Ring A in testosterone to aromatize to form estrogen?
A: aromatase.

Q: Testosterone is precursor to what two steroid hormones?
A: estradiol (estrogen) and DHT (needed for external genitalia development in males)

Q: What enzyme converts testosterone to its active form DHT?
A: 5-a-reductase

Q: What are symptoms of 5-a-reductase deficiency?
A: a genetic male that appears female.

Q: What is the main source of estrogen production during pregnancy?
A: Placenta.

Q: Menopausal women produce estrogen as estrone. From what is estrone derived?
A: androstenedione

Q: What are the four Congenital Adrenal Hyperplasias (CAH) (defect in steroid hormone synthesis from cholesterol)?
A: 3-b-hydroxysteroid DeH, 17-a-hydroxylase, 21-a-hydroxylase, 11-b-hydroxylase deficiencies.

Q: What is the most common congenital adrenal hyperplasia (CAH)?
A: 21-a-hydroxylase deficiency

Q: Which two congenital adrenal hyperplasias (CAH) cause female-like genitalia?
A: 3-b-hydroxysteroid DeH and 17-a-hydroxylase deficiency, because these enzymes are needed before making testosterone.

Q: Which two congenital adrenal hyperplasias (CAH) cause overproduction of testosterone, and hence male-like genitalia?
A: 21-a hydroxylase and 11-b-hydroxylase deficiency, because these prevent aldsterone and cortisol from being made from progesterone and 17-a-hydroxyprogesterone, which cause them to keep making testosterone instead.

Q: How does deficiency in 21-a-hydroxylase and 11-b-hydroxylase cause adrenal hyperplasia?
The decrease in aldosterone and cortisol prevents negative feedback of ACTH → causes adrenal hyperplasia.

Q: A partial deficiency in 11b or 21-a-hydroxylase will cause virilization. How about complete deficiency?
A: hyponatremia and hyperkalemia. (very very dangerous)

Q: What syndrome is due to hypersecretion of ACTH, which cause overproduction of corticosteroids?
A: Cushing’s Syndrome… you get obesity and buffalo hump.

Q: What disease is caused by adrenocortical insuffiency?
A: Addison’s disease. It causes hypoglycemia, imbalance in Na and K, dehydration → hypotension.

Q: What are the two types of adrenocorticoids (same as corticosteroids)?
A: mineralocorticoids (i.e. aldosterone) and glucocorticoids (i.e. cortisol)

Q: where is the C=O of aldosterone derived from?
A: the oxidized OH group on C-3 during the 3-b-hydroxysteroid dehydrogenase step turning pregnenolone to progesterone.

Q: What enzyme deficiency causes mineralocorticoid production to be elevated?
A: 17-a-hydroxylase defiency… because it shunts all pregnenolone to become 11-deoxycorticosteroid. Too much aldosterone causes too much retention of sodium and fluids, leading to hypertension.

Q: What process does cortisol activate?
A: gluconeogenesis. It degrades body proteins to provide carbon for gluconeogenesis.

Q: Hydroxylations require ____ while Oxidations require ______.
A: Hydroxylations require NADPH while oxidations require NAD+

Q: What stimulates the production of aldosterone?
A: angiotensin, low Na/K ratio, low extracellular volume, low blood pressure.


Q: What is the difference between reproductive cloning and therapeutic cloning?
A: reproductive cloning is used to make completely new organisms, while therapeutic cloning is used to make cells for transplantation.

Q: Where are embryonic stem cells harvested from?
A: Inner cell mass (ICM) of blastocyst.

Q: What do you combine with what to perform therapeutic cloning?
A: Combine nucleus of patient with egg (minus nucleus) of donor → stimulate to develop blastocyst.

Q: How do you make a transgenic mouse?’
A: Follow these steps:

1. A: Isolate eggs after they’ve been fertilized
2. Inject foreign DNA with needle into large male pronucleus (remember egg has 2 pronucleus one from each parent). DNA doesn’t replace any gene. It just adds on… somewhere random.
3. Put egg in foster mother.
4. DNA tends to integrate only after 1-2 cell divisions occur, so resulting mouse only have part of its cells transgenic.
5. Imbreed to make fully transgenic mouse.

Q: How do you make knock-out mouse?
A: Follow these steps:

1. Take embryonic stem cells from a certain mouse.
2. Put a mutant gene into the stem cell. It will recombine and replace a target gene.
3. A chimeric mouse is born, with cells from both the replaced gene and original gene. Called a Chimeric Mouse.
4. If the gene contribute to germ line… collect transgenic eggs or sperm
6. Use that sperm or egg to make a heterozygous mutant mouse.
7. Imbreed the heterozygous mutant mouse to make a generation of purely transgenic mice (knockout mouse)

Q: what is the difference between transgenic mouse and knock-out mouse?
A: transgenic mouse just has an extra gene, not a replaced gene. Transgenic mice are made by injecting DNA into a fertilized egg. Knockout mice are made by putting mutant gene into stem cell, then transferred to an embryo.

Q: What do researchers add to the transgenic DNA to show that it has been inserted?
A: reporter gene

Q: What happens when you don’t have Lmx1b?
A: affects development of dorsal limb structures . LMX1B is a conserved non-coding sequence found across species – shows role in gene regulation.

Q: What are four ways for gene therapy?
A: Gene augmentation therapy, Gene mutation correction, Inhibition of gene expression, Direct killing of disease cells.

Q: What is the difference between gene augmentation and gene mutation correction?
A: gene augmentation simply adds a gene to a cell that didn’t have it before. Gene mutation correction adds the correct gene to a cell that had a bad gene to begin with… in hopes it will go through homologous recombination.

Q: What is inhibition of gene expression therapy?
A: if disease cell has harmful gene (like activated oncogenes), use antisense oligonucleotide to bind to the mRNA?

Q: How do you kill disease cells with gene therapy?
A: you can either add toxin gene to cell, causing them to express toxins that kill themselves. You can also add a prodrug gene, that makes them susceptible to a certain drug.

Q: What determines whether you should do an in vivo or ex vivo gene therapy?
A: accessibility of the target cell and the genetic defect.

Q: If you use a retroviral vector for gene therapy, what retroviral genes do you replace with therapeutic gene?
A: gag, pol, env.

Q: Why is it necessary to separate the Gag/pol and env constructs?
A: to avoid producing a virus (viral DNA). You will still have all the viral proteins that would help the new transgenic vector to bud off, but without the viral DNA.

Q: How can liposomes be used in gene therapy?
A: they can carry the vector, then fuse with the target cell.

Q: Adenovirus vectors are good in that they won’t integrate into the genome and they have a larger insert size. What is a disadvantage?
A: they must be given at large doses, which is an immunity concern.

Q: Why do many cases of retroviral cause leukemia in gene therapy?
A: because the gene you insert spreads in a virus-like fashion.

Q: How do you fight brain tumor with in vivo gene therapy?
A: implant the tumor with Vector Producer Cells (VPC). Cells produce a virus, which infects tumor cells but not normal cells. Then you treat the cells with Gancyclovir, which kills the viral-infected cells.

Q: What are the benefits of using gene chips?
A: by detecting which genes are activated, you can distinguish between similar diseases. You can also test to see whether or not a cancer will benefit from a certain treatment.

Q: What do gene chips track?
A: they track genetic variation.


Q: What is the difference between Malformation, Disruption, and Deformation (which are all structural defects)?
A: Malformations are caused by genetically abnormal development (i.e. cleft palate). Disruption are caused by disruption in developmental process (like amniotic bands). Deformation is caused by mechanical force (like uterine constriction)

Q: What is a Sequence?
A: structural defect that leads to multiple secondary effects.

Q: What is a dysplasia?
A: abnormal organization of cells, tissues, and their morphological consequence. i.e. achondroplasia.

Q: What is a syndrome?
A: many anomalies that is caused by a single cause.

Q: What is an association?
A: many malformations that seem to occur often together, but we don’t understand yet.

Q: What is the cause of Potter sequence?
A: renal agenesis (no kidney development) → oligohydramnios

Q: Which clinical problems are solely environmental?
A: Disruption, Deformation

Q: Which clinical problems are solely genetic?
A: Malformation, Dysplasia, Syndrome

Q: Which clinical problems are both genetic and environmental?
A: Sequence and Association.

Q: What are Bosley-Salih-Alorainy Syndrome (BSAS) and Athabascan Brainstem Dysgenesis Syndrome (ABDS) caused by?
A: homozygosity for HOXA1 null mutation

Q: What causes Hand-Foot-Genital Syndrome
A: HOXA13 mutation

Q: What is a homeodomain?
A: Genes that regulate pattern of development

Q: What is a paired-box gene (PAX)?
A: A gene that consist of a paired box and a homeodomain. Codes for transcription factor. Their deficiency causes developmental abnormalities.

Q: Mutation in PAX3 causes what syndrome?
A: Waardenburg Syndrome – most common form of inherited deafness.

Q: Mutation in PAX6 causes what?
A: Aniridia

Q: What do heterozygotes of PAX6 mutation have? Homozygotes?
A: heterozygotes develop aniridia. Homozygotes do not develop eyes at all.

Q: TBX genes code for what?
A: T-box transcription factors for the development of different structures.

Q: What syndrome is caused by heterozygous TBX3 mutation?
A: Ulnar Mammary Syndrome. Upper limb malformation.

Q: What syndrome is caused by heterozygous TBX4 mutation?
A: Small Patella Syndrome. Lower limb malformation.

Q: What syndrome is caused by TBX5?
A: Holt-Oram Syndrome – abnormal carpal bone.

Q: What TBX gene controls upper limb? Lower limb?
A: TBX5 does upper limb (because it’s higher). TBX4 does lower limb.

Q: What malformations are due to TBX22 mutation (X-linked)?
A: Cleft Palate and Ankyloglossia (tongue tie)

Q: What syndrome is caused by deficiency in transcription factor LMX1B?
A: Nail Patella Syndrome.

Q: What dysplasia is caused by deficiency in transcription factor RUNX2 (CBFA1)?
A: Cleidocranial Dysplasia – no clavical. Strange-shaped cranial bone, supernumerary teeth.

Q: What does the drug thalidomide do?
A: it blocks limb bud cell proliferation – so too much will cause amelia.

Q: Mothers taking AED (Anti-epileptic drugs) can cause birth defects like what?
A: Fetal Valproate Syndrome

Q: Mothers drinking alcohol will cause what syndrome in fetus?
A: Fetal Alcohol Syndrome

Q: What are two mutations associated with neural tube defect?

Q: Mutation of what gene is a frequent cause of holoprosencephaly?

Q: Van de Woude Syndrome presents cleft palate. What is the mutation?
A: IRF6, which normally bind to transcription factor AP-2. Mutation reduces this binding.

Q: What is normally sweeped to the left around the primitive node by cilia?
A: SHH and FGF-8.. if this isn’t sweeped, causes laterality problems like Kartagener Syndrome.

Q: How is symmetry related to malformation?
A: The more symmetry there is to a malformation, there greater the chance that it has a genetic cause.


Q: What’s the difference between plasma and serum?
A: Plasma can clot, serum cannot. Serum is the liquid left over after blood has clotted.

Q: What is a fancy name for scabbing?
A: hemostasis. Followed by its own removal then fibrinolysis (wound healing)

Q: Do platelets have nucleus?
A: no. They are, however, full of secretory granules

Q: What are two activators of platelets?
A: collagen and thrombin

Q: What do activated platelets expose on the outer leaflet of their plasma membrane?
A: phosphatidylserine, used for assembling.

Q: How do GP1b on platelet membrane bind to subendothelial collagen from a wounded vessel?
A: via von Willebrand Factor (VWF)

Q: How do platelets stick to each other?
A: via GPIIb/GPIIIa and fibrinogen.

Q: What is the mutation in GPIIb/GPIIIa genes called?
A: Glanzmann’s Thrombasthenia.

Q: How does the anti-thrombotic agent Plavix work?
A: It interferes with GPIIb/GPIIIa/fibrinogen connections.

Q: What two components form a complex in circulation?
A: vWF and Factor VIII

Q: What is a deficiency in von Willebrand Factor called?
A: von Willebrand Disease – the most common congenital bleeding disorder.

Q: What is a positive feedback regulator of the clotting cascade?
A: Thrombin, which is made down the cascade.

Q: Where are most clotting factors made?
A: In liver.

Q: What ion is required for most steps of the blood clotting cascade?
A: Calcium.

Q: What kind of proteases are blood clotting proteases?
A: serine proteases – has an activated serine that does all the catalytic reactions. Cuts at arginine residue.

Q: What cleaves prothrombin (Factor II) into thrombin (Factor IIa)?
A: Factor Xa and Va

Q: What is the cell-surface protein that triggers blood clotting when exposed to plasma?
A: tissue factor (TF) – complexes with VIIa

Q: Where are tissue factors located?
A: adventitial cells of almost all blood vessels larger than capillaries.

Q: How can thrombin inhibit coagulation cascade?
A: thrombin binds to thrombomodulin on vessel surface. Activates Protein C. Protein C-Protein S complex destroys Factors Va and VIIIa.

Q: Hemophilia A is a deficiency in which Factor?
A: Factor VIII. Caused by intrachromosomal Inversion.

Q: Hemophilia B (Christmas Disease) is a deficiency in which Factor?
A: Factor IX

Q: What’s a chant to remember the blood clotting cascade?
A: TF-7-9-8-10-5-thrombin-fibrin-13-crosslink

Q: People with Factor V Leiden mutation have a mutated Factor V that cannot be destroyed by Activated Protein C. What is the result?
A: They have a much greater risk of deep-vein thrombosis.

Q: Describe the structure of Fibrinogen.
A: a dimer, each unit with Aa, Bb, and gamma chains. A and B are really negatively charged.

Q: How do fibrinogens not stick together?
A: the A and B are really negatively charged… repel each other.

Q: What does Thrombin do to Fibrinogen to make Fibrin?
A: It cleaves off the really negatively charged A and B fibrinopeptides. The Fibrins then aggregate into “soft” clot.

Q: Which Factor covalently crosslinks fibrin?
A: Factor XIII – making the “soft clot” into a “hard clot.”

Q: What reaction does Factor XIIIa do to make a “hard clot” out of fibrin?
A: it is a transglutamidase.

Q: What is the most important serpin (serine protease inhibitor) in the body?
A: Antithrombin – it inactivates factor Xa and thrombin.

Q: What enzyme on the endothelial surface activates antithrombin?
A: Heparin.

Q: What degrades fibrin clots?
A: plasmin

Q: What two serine proteases converts plasminogen into plasmin?
A: tPA (tissue-type plasminogen activator) and uPA (urinary-type plasminogen activator)… used to treat stroke and myocardial infarction.

Q: What vitamin is needed during coagulation?
A: Vitamin K does carboxylation (“Karboxylation”) of prothrombin, C, S, VII, IX, X

Q: What drugs antagonize Vitamin K to prevent coagulation?
A: Coumarin drugs (warfarin)