Specialization Of Proteins Ii (Foundations Exam 1)

Front 1

erythrocytes
composition of blood

Back 1

35% of the volume of whole blood

Front 2

reticulocytes

Back 2

- formed from erythropoietic precursor cells (contain nucleus and protein synthesis machinery)
- precursor to erythrocytes
- do not have nucleus
- contain ribosomes
- mature into erythrocytes about a day after entering blood --> lose mitochondria and ribosomes

Front 3

erythrocyte features

Back 3

- no intracellular organelles
- plasma membrane
- discoid in shape
-purpose: transport oxygen from lungs to tissues and return carbon dioxide from the tissue to lungs
- important protein: hemoglobin
- other proteins: enzymes of glycolysis

Front 4

total hemoglobin in blood value

Back 4

14-18 g/dL
--> iron-deficiency anemia in females < 10g/dL

Front 5

clincal presentation of iron-deficiency anemia

Back 5

paleness (due to reduced amounts of oxygenate hemoglobin), fatigue, weakness

Front 6

biological membrane composition

Back 6

45% lipid
45% protein
10% carbohydrate

--> neutral and negative sugars contribute to overall negative charge of surface

Front 7

membrane bilayer

Back 7

- the lipids form a layer
- proteins are embedded in this bilayer and carbohydrates are attached to the outer surface

Front 8

integral proteins

Back 8

- span the lipid bilayer with domains that extend on both the inside and outside of the cell
- trans-membrane domain looks like a spring --> alpha helix secondary structure
- the rest of the domains are globular

Front 9

lipid-anchored proteins

Back 9

- covalently attached to the lipid
- anchored to intracellular or extracellular surface of membrane

Front 10

carbohydrates

Back 10

- attached to lipids and proteins on the outside surface
- glycolipids and glycoproteins are important in cell-cell recognition

Front 11

erythrocyte membrane features

Back 11

- membran proteins may be separated via polyacrimade gel electrophoresis (PAGE)
--> distinct band patterns

Front 12

anion exchange protein

Back 12

- band 3
- transmembrane protein that crosses the membrane multiple times
- dimer --> forms channels
- exchange chloride ion (Cl-) with bicarbonate (HCO3-)
-->bicarbonate is derived from CO2 product of aerobic metabolism
-->bicarb is exchanged for chloride in lungs
- N-terminal end of band 3 interacts with hemoglobin, band 4.1 protein and ankyrin

Front 13

spectrin

Back 13

- primary protein that comprises the cytoskeletal structure of RBC membrane
- heterodimers (alpha chain and beta chain)
- binds ankyrin, actin, and band 4.1 protein

Front 14

ankyrin

Back 14

- binds to band 3 --> secures spectrin to membrane

Front 15

actin in RBCs

Back 15

- double helical structure
- interacts with the end of spectrin dimer
- also binds 4.1 protein

Front 16

band 4.1 protein

Back 16

- interfaces with glycophorins in membrane and membrane phospholipids
--> helps connect cytoskeleton and lipid bilayer

Front 17

myoglobin

Back 17

-found in muscle tissues where it stores O2

Front 18

hemoglobin

Back 18

- found in the blood, especially in RBCs, and carries O2 from the lungs to the tissues and CO2 from tissues to the lungs

Front 19

Heme

Back 19

- porphyrins
- iron atom liganded to 4 nitrogen atoms in a pyrrole structure
- active iron is reduced form Fe 2+ --> ferrous iron

Front 20

ferrous iron

Back 20

- active form of iron in heme
- six valence electrons
--> 4 bind to heme
--> 5th binds to histidine
--> 6th valence electron binds to oxygen (O2)

Front 21

ferric iron

Back 21

Fe 3+ --> oxidized form
--> ferrihemoglobin or methemoglobin

Front 22

myoglobin

Back 22

- 75% of structure is comprised of alpha helices
- globin proteins contain eight distinct alpha helical regions (A-H)
- distal and proximal histidines
- interior amino acids are non-polar
- structure driven by hydrophobic forces --> major stabilizing force

Front 23

hemoglobin structure

Back 23

- tetrameric protein--> four polypeptide chains
- chains derived from two families
1. includes alpha and zeta chains
2. includes beta, delta, gamma, epsilon chaings
- each chain contains heme prosthetic group
- adult hemoglobin (HbA1) is alpha2 beta2

Front 24

alpha gene cluster

Back 24

- alpha 1 and alpha 2 are duplicated genes both of which are transcribed
- zeta gene is only expressed at the embryonic stage

Front 25

beta gene cluster

Back 25

- delta gene is found in 3-5% of adult Hb --> HbA2
- Gϓ and Aϓ refer to duplicated fetal genes that differ in a single amino acid and are found in fetal HbF (alpha2 gamma2)
- epsilon gene is only expressed at the embryonic stage

Front 26

Beta family vs alpha family

Back 26

beta family has higher affinity for oxygen than alpha family

Front 27

thalassemias

Back 27

autosomal recessive diseases
--> both copies of a globin gene must be mutated
--> reduced rate of globin chain synthesis
--> causes anemia due to improperly assembled and abnormal tetramers

Front 28

alpha thalassemias

Back 28

four genetic loci: two alleles of alpha 1 and alpha 2
- most commonly involve gene deletions
--> reduction in alpha chains results in excess beta chains in adults and excess gamma chains in newborns

Front 29

silent (asymptomatic) carriers

Back 29

only one of the four alpha loci are affected
--> sufficient to permit normal Hb production

Front 30

alpha thalassemia minor (trait)

Back 30

- two alpha globin loci are affected
--> mild microcytic (small RBC size) hypochromic anemia

Front 31

alpha thalassemia intermedia
or
hemoglobin H disease

Back 31

- HbH (beta4) and Hb Barts (gamma4)
- when three loci are affected
-unstable and high affinity for oxygen --> not delivered to tissues
--> microcytic hypochromic anemia, cells and Heinz bodies (damaged precipitated Hb)

Front 32

alpha thalassemia major

Back 32

- if all four loci are affected--> fetus cannot survive

Front 33

beta thalassemias

Back 33

if beta chain production is reduced --> delta chains are able to increase in expression

- beta and delta genes are adjacent on chromosome

Front 34

beta thalassemia minor

Back 34

only one beta globin allele is mutated
--> mild microcytic anemia (asymptomatic)

Front 35

beta Thalassemia intermedia

Back 35

affected individuals can often manage a normal life with occasion transfusions

Front 36

beta thalassemia major
or
Cooley's anemia

Back 36

both alleles have mutations
--> severe microcytic, hypchromic anemia
--> untreated leads to death before 20
--> transfusion dependent