AAs, proteins, hemoglobin, collagen Flashcards

Question

Which enzymes assist protein folding? Briefly explain their function.

Answer 1

_assisted by:_ * **chaperones**: move hydrophobic regions inside * **protein disulfide isomerase**: catalyzes formation/breakdown of disulfide bonds * **proline-cis, trans-isomerase**: isomerizes trans to cis peptide groups

Answer 2

**heat-shock-proteins** → more produced during high T → prevent protein denaturation

Answer 3

* _prim. structure:_ repeated **(Gly-X-Y)_n** **sequence** * _sec. structure:_ **left handed collagen helix** * _tert. structure:_ **right-handed triple helix**, stabilized by: * _quart. structure:_ **collagen microfibrils/fibrils/fibers**

Answer 4

(**Gly**-X-Y)_n, where X and Y _mostly_ **Pro** and **HyPro**

Answer 5

* **hydroxylation** of * Pro → _HyPro_ * Lys → _5-OH-Ly_s * ____**glycolysation** of * Lys, receives glucose/galactose

Answer 6

via **oxidative carboxylation** w/ **hydroxylation** α-KG + Pro + O₂ → succinate + HyPro + CO₂

Answer 7

**_scurvy_** dietary _vit C deficiency_ bc is cofactor for **Pro/Lys hydoxylase** _{→ severe instability of collagen fiber, causing bleeding gums, swelling joints, poor wound healing, death}

Answer 8

_3 left_ handed collagen helices form _**right** handed_ **procollagen**, eventually **tropocollagen** _triple helix_ * **interchain H-bonds** btw peptide groups of Gly and Pro * **cross links** btw 2 Lys

Answer 9

both are right handed triple helix formed by 3 left handed collagen helices, BUT procollagen has **globular terminals** which need to be _cut_ by _procollagen peptidase_ so the 3 helices can polymerize → forming tropocollagen

Answer 10

by **polymerization of tropocollagen** stabilized by **cov. lysinonorleucin bridges**, and to a minor extent also _interchain H bonds_ btw OH-groups of HyPro

Answer 11

_by **Lys oxidase**_ 1. NH₂ groups of Lys converted to _aldehydes_ 2. condensated w/ second Lys (formation of _Schiff base_, linking 2 polypeptides) 3. reduced to **lysinonorleucin bridges**

Answer 12

**_Menke's syndrome_** dietary _deficiency of Cu²⁺_ required by **Lys oxidase** _{→ def. of lysinonorleucin bridges btw tropocollagen fibers, causing kinky hair, growth retardation}

Answer 13

* **_osteogenesis imperfecta_** incomplete procollagen formation → fragile bones * **_Ehler-Danlos syndrome_** decr. activity of procollagen peptidase → stretchabile skin, hypermobile joints

Answer 14

**planar cyclic tetrapyrrole** linked by **methyne bridges,** has **Fe2+ center**

Answer 15

**monomer** w/ **8 α-helices A-H** (4 terminated by Pro) + **heme** in center * _non-polar_ side chains inside * _polar side_ chains outside _**BUT**:_ **distal His E7, proximal His F8** close to heme iron

Answer 16

_**Fe²⁺** can form 6 coordinate bonds_ 4 w/ heme, 1 w/ proximal His, 1 w/ O₂ _BUT:_ if Fe²⁺ oxidized to Fe³⁺ (unphysiological), only able to bind H₂O **→ moves towards proximal His F8 when O₂ binds**

Answer 17

* _proximal His F8:_ * *holds heme** * _distal His E7:_ * *weakens CO binding** to the heme ring (b/c endogenous CO occupies 1% of all sites)

Answer 18

_**tetramer** consisting of_ * always pair of **α subunits** * **+** either pair of **β, γ,** δ, **β^s** ⇒ can carry 4 O₂ _NOTE:_ β subunit has high homology to myoglobin

Answer 19

* **HbA1** (_normal adult_ Hb): **α₂β₂** * **HbA2** (_minor adult_ Hb): **α₂δ₂** * **HbF** (_fetal_ Hb): **α₂γ₂** * **HbS** (_sickle cell_ Hb): **α₂β^s₂**

Answer 20

_allosteric behavior_ triggers **homotropic** **cooperativity** * **R state** = relaxed, Hb can be easily saturated w/ O₂, stabilized by _secondary bonds_ * **T state** = tense, Hb easily releases O₂, able to bind _2,3-BPG_, stabilized by _ionic bonds_

Answer 21

formed from 1,3-BPG (intermediate of glycolysis) in _peripheral tissue whith low P_O2_ binds to center of T state hemoglobin, forming _add. ionic bonds_ ⇒ **prevents re-binding of O₂ to hemoglobin in peripheral tissue**

Answer 22

in **_deoxyHb (T state)_** Fe²⁺ is out of plane of heme 1. binding of 1st O₂ induces **Fe²⁺** **to move into plane** of heme 2. movement transmitted to His F8 and F helix, **breaks ionic bonds** btw all 4 subunits → changes in protein structure = **_oxyHb (R state)_** ⇒ increased affinity for O₂ of other subunits, _ALSO:_ 2,3-BPG unable to bind now

Answer 23

transports O₂ in blood **sigmoidal curve** due to cooperative behavior and 2,3-BPG * _high P_O2 in pulm. capillaries:_ Hb becomes easily saturated due to succ. incr. affinity for O₂ * _low PO2 in syst. capillaries:_ 2,3-BPG in those tissue, keeps Hb from binding much O₂, facilitates O₂ release into tissue

Answer 24

storage of O₂ in muscle tissue as reserve, has _hyperbolic curve_ **releases O₂ only at very low P_O**₂(i.e. during exercise) _NOTE:_ Hb would behave just the same if there were no 2,3-BPG in peripheral tissue

Answer 25

describes the **decr. affinity of Hb when P_CO2 incr./pH decr.** → easier release of O₂ in tissue w/ high consumption rates _i.e. during exercise:_ incr. metabolic activity causes * ↑ **T** * **↑ [CO₂]**, **↓ pH** * **↑** production of **2,3-BPG** ****⇒ H⁺ binds to Hb → ionic bonds reform, T state _right shift_ of dissociation curve

Answer 26

* α₂γ₂ * has **weaker BPG binding** b/c _His₁₄₃_ replaced by **Ser₁₄₃** ⇒ **higher affinity for O₂** in placenta, but also limited O₂ delivery → changes structure after birth ****

Answer 27

**proximal His F8 replaced by Tyr** Tyr oxidizes Fe²⁺ to _Fe³⁺_ → _H₂O binds_ instead of O2, lethal

Answer 28

* α₂β^s₂ * surface **Glu₆ replaced by Val₆** → forming sticky hydrophobic patch on β^s _deoxyHb_ aggregates, forming long sickle shaped fibers which are prone to lysis in splenic sinusoids ⇒ causing **_sickle cell anemia_**

Answer 29

**autosomal co-dominantly inherited** * heterozygotes: have ∽ 1% HbS, but are resistant to _malaria_ * homozygotes: die

Answer 30

**autosomal recessive blood disorder** → defective synthesis of Hb, causes improper O₂ transport, anemia

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AAs, proteins, hemoglobin, collagen Flashcards

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