Medical Biochemistry Lecture 1-9

Front 1

Physiological pH

Back 1

7.4

Front 2

Buffer

Back 2

Consists of weak acid and its conjugate base. Works best at 1 +/- pH unit from its pKa

Front 3

Three things that determine effectiveness of buffer

Back 3

1) pH of solution

2) concentration of buffer (more concentration, better it's going to work)

Front 4

Phosphate system

Back 4

Major buffer regulatory of the cytosol

Front 5

What are the normal levels of pH, bicarb, and co2 in blood

Back 5

pH: 7.4

bicarb: 24mM

Co2: 1.2mM

Front 6

Henderson Halshback equation

Back 6

how to do problm on 27 (lecture 2)

Front 7

6 reactions in the coagulation pathway

Back 7

1) thrombin-fibrinogen-fibrin

2) factor 13a

3) hemophilia

4) anti-protease system

5) auto-regulation of thrombin

6) fibrinolysis

Front 8

Name 5 anti-congulators

Back 8

1) Clopidogrel

2) Aspirin

3) Nitric Oxide

4) Warfarin

5) Heparin/Glycosaminoglycans

Front 9

vWF

Back 9

Von Willebrand factor. circulating protein, helps to bind platelets to collagen and each other resulting in activation of the platelets and release of various activators

Front 10

Why doesn't undamaged vascular endothelium clot under normal circumstances?

Back 10

Collagen fibrils are not exposed, and other activating factors such as ADP are not present in sufficient amounts. Also undamaged vessels are giving off nitric oxide and prostoglandins, which prevent the platelets from sticking to it

Front 11

Know collagen vWF and intrinstic and extrinsic pathways

Back 11

See print outs

Front 12

What are the 6 zymogens of both pathways (intrinsic and extrinsic)

Back 12

Factors: 12, 11, 9, 7, 10, 2 are zymogens of serine proteases

Front 13

What are the 4 factors that help to activate thrombin

Back 13

Prothrombin, factor Va, factor Xa, calcium, anionic phospholipids

Front 14

Where is prothrombin synthesized

Back 14

It is synthesized in the liver and contains 10 Glu residues

Front 15

What specific factor cleaves prothrombin to thrombin?

Back 15

Xa (Xa is made when intrinsic and extrinsic pathways send their activated X over). Starting of the common pathway

Front 16

How does Fibrinogen become fibrin?

Back 16

Thrombin cleaves fibrinogen, which has 2 tripeptide units.

Fibrin monomers go through a conformation change in the middle globular domain, this increases its affinity towards the terminal domain of other fibrin monomers (makes them stick together better)

Front 17

How does soft clot become hard clots?

Back 17

Factor 13a stabilizes and converts soft clot to final clot by covalent cross-linkages between specific glutamine residues on one monomer to lysine residues on another monomer

Front 18

How does vitamin K help in clotting cascade?

Back 18

Vitamin K is needed to synthesize Gla (carboxyglutamate). Gla then combines with calcium to form a complex that allows interactions with acidic membrane lipids that lead to correct tertiary and quaternary protein structures that are recognized by other proteins in the pathway.

Factors that are dependent on Gla are Thrombin (2), 7, 9, and 10.

Calcium is considered a co-factor

Front 19

Explain the role Dicoumarol (I) and Warfarin (II) play in platelet formation

Back 19

These are 2 analogs of vitamin K, and they inhibit the formation of Gla. Thus, the factors thrombin, 7, 9, 10 can't be made. This makes these drugs excellent anti-coagulants.

Front 20

Physiological effect of inhibiting Gla production

Back 20

Normally free Gla peptides in the blood will signal new production of Gla proteases in the liver. But blocking the Gla modification by the drugs prevent any new Gla from being secreted, and this limits the number. So clotting can still happen, but the amplification is reduced

Front 21

Hemophilia

Back 21

Genetically inherited disease characterized by the inability to form blood clots.

This is due to defective factor 8 (hemophilia A), or factor 9 (hemophilia B). Hemophilia 8 is the most common form

Both of these factors are in the intrinsic pathway, so the extrinsic pathway still works. So when a wound happens, disproportionate clotting factor response leads to entire process becoming impaired

Front 22

Anti-protease system

Back 22

Protein protease inhibitors are present in sufficient amount in blood to make sure random thrombin activation doesn't happen.

Front 23

AntithrombinIII

Back 23

AntithrombinIII binds tightly and inactivates thrombin. This complex is then cleared fro circulation in the liver

Administration of heparin promotes the association between antithrombin III and thrombin (facilitates anti-coagulantation)

Front 24

Protein C

Back 24

Protein C is activated by Thrombomodulin and calcium (thrombomodulin is made when thrombin and endothelial cell protein combine).

Protein S makes Protein C, which will proteolyze and inactivate Factors 5a, and 8a. Inactivation of 5a, inhibits activation of 10a, which prevents prothrombin from being converted to thrombin.

Combination of antiproteases and protein C ensures only the site of injury is currently experiencing clotting

Front 25

Anti-proteases

Back 25

Another regulatory complex that down regulates activated clotting factors in blood so activation-inactivation can exist in equilibrium

Front 26

How are clots dissolved? Fibrinolysis

Back 26

Protease tissue plasminogen activator (tPA) binds with high affinity to fibrin clots along with plasminogen. This activates plaminogen to plasmin, which digests the fibrin.

After dissolving a region of clot, the plasmin-tPA falls off, so the whole clot doesn't get digested right away.

Front 27

What are the two classes of protein in a phospholipid bilayer?

Back 27

Peripheral (extrinsic) [can be removed with some mild detergent] and Integral protein, glycophorin (intrinsic proteins) [can't be removed]

Front 28

Flipasses

Back 28

Lipids move from one monolayer to the other by flippase proteins

Front 29

Glyophorin

Back 29

Single transmembrane-segment protein with globular domains on either end

These globular heads constitute ABO and MN blood groups. Located on the erythrocyte, single helical transmembrane segment

Front 30

Bacteriorhodopsin

Back 30

7 transmembrane helical segments. Patches of Holobacterium halobium

Front 31

Porins

Back 31

They are proteins that form pores and are found in both gram-negative bacteria and mitochondrial outer membrane

Front 32

Facilitated diffusion

Back 32

They only occur in the favored direction, but the proteins facilitate transport and thus increase the rates of transport

Front 33

Sodium Potassium pump

Back 33

Three sodium out, two potassium inside cell. Crucial for all organs, especially for neural tissue and the brain

Front 34

Calcium Transport

Back 34

Calcium is released, block tropmyosin interaction. Need to get calcium back in, otherwise rigourmortis sets in. ATP is hydrolyzed to get calcium from low to high concentration

Front 35

Gastric H, K+ATPase

Back 35

Hydrolyzing ATP, swapping hydrogen ions and potassium ions. Proton-pump inhibitors, drugs of those kind end in ozole. Blocks hydrogen/potassium ATPase. Prevents stomach acid to going to pH of 1

Hydrogen ions into the gut, and potassium ions out

Front 36

Osteoclast Proton Pump

Back 36

Osteoclasts break down bone tissue, and osteoblasts build bone back up. They do it by secreting acid and ATP driven proton pump does this. Help to push calcium from low to high concentration. From blood to bone, for instance if you break your bone

Front 37

When does skeletal muscle require insulin?

Back 37

Skeletal muscle when it's active does not require insulin, but it does require it when it is resting. Insulin helps to bring GLUT proteins to the surface from Golgi and helps cell take it glucose

Front 38

3 basic intracellular cascade events

Back 38

1)Ligand binds to receptor, binds to adenosine cyclase, which converts ATP to cyclicAMP, this activates protein kinase A, and this affects transcription

2) Phosphokinase A2 activates aracdonic acid on carbon 2 of phospholipid

3) phosphokinase C activates PkC and IP3. This is involved in affecting calcium

Front 39

Albumin

Back 39

Regulation of water movement between tissues and blood

Front 40

Globulins

Back 40

Immune system or transport molecules

Front 41

Colloid

Back 41

Liquid containing suspended substances that don't settle out

Front 42

Granulocytes

Back 42

Neutrophils, basophils, eosinophils

Front 43

Agranulocytes

Back 43

Lymphocytes, monocytes

Front 44

What are the precursors in heme synthesis

Back 44

Glycine and succinyl-CoA

Front 45

One polypeptide chain

Back 45

monomeric protein

Front 46

Homomultimer

Back 46

one kind of chain

Front 47

heteromultimer

Back 47

two or more different chains. ex is hemoglobin

Front 48

How is amino acids read

Back 48

N to C terminus

Front 49

How is DNA read and synthesized

Back 49

Synthesized 5 to 3, read 3 to 5

Front 50

What two structures are stabilized by hydrogen bonds?

Back 50

Alpha helix and beta sheets

Front 51

Fibrous Proteins

Back 51

Parallel to single axis, mechanically strong, insoluble, and plays a structural role in nature

Front 52

What is the principal component of connective tissu

Back 52

tendons, cartilage, bones and teeth

Front 53

Basic unit of tropocollagen

Back 53

three intertwined polypetide chains, unique amino acid composition

Front 54

4 facts about collagen

Back 54

1) every 3rd residue is Gly

2) Proline and HyPro make up a large amount of resides

3) 4/3hyoxyproline, and 5 hydroxylysine are unusual amino acids found

Front 55

When is PTT used

Back 55

PTT is used in the intrinsic pathway

Front 56

Heparin

Back 56

anticoagulant of intrinsic pathway

Front 57

PT

Back 57

Used in extrinsic pathway

Front 58

Warfarin

Back 58

Gets used in the extrinsic pathway as an anticogulant

Front 59

Two things that break down plasmin

Back 59

Alpha 2 antiplasmin

Alpha 2 microglobin