1

Biochem sheet (2)

Made by :duaa migdadi

corrected by lama nedal

DATE : 25/9

2

According to last lecture, we should know that essential amino acids are found in meats.

essential a.a ,, each one has one types of a.a alldo not have Plants -

EX. Rice is source of lysine.

Beans and beef rich of methionine.

- Essential a.a are found in animals protein

النهم مشكله عندها ما الفئة وهاي(vegetarian) الحمراء اللحوم بتناولوا ما فقط االول نوعين: فهمه النباتيين لالشخاص بالنسبة مالحظه: **

الفئه فهاي(vegans) الثاني النوع اما, essential a.a))تحتوي جميع الحليب مشتقات مثل اخرى مصادر من االمينيه الحموض بيعوضوا

من شي اي بيتناولوا ما النهم المشكله عندهم يلي

كمكمل غذائيفيجب اخذهم خارجيا . b12 فيتامين في بالنقص لالصابه معرضين وبالتالي حيواني مصدر

*vitamin B12 : from animals origin

-less vitamin required ( we need just 3 micro gram / day )

- it is amount which storage in liver enough our body to 6 months.

4:45

protein structure dimensional-3 Now we wil discuss

**primary structure : which is the sequence of a.a in a polypeptide chain , read from the N-terminal end to

the C-terminal end .

-amino acids sequence determine the functions of protein , so if there deficiency or replacement in one a.a

functions affected .

A striking example of the importance of primary structure is sickle-cell anemia, a disease caused by a change

in one amino acid in each of two of the four chains of hemoglobin, as we studied hemoglobin contain two

alpha chains and two beta chains so if there replacement at position 6 … sickle RBC will found .

Normal RBC is biconcave and it is functioning well , but any defect in one a.a in one of the hemoglobin

chains then the whole hemoglobin function will be destroyed .

In sickle cell anemia RBC will be sickle-shaped so compact together and stuck in blood vessels so these

vessels will be unable to transport oxygen effectively which lead to anemia and other problems so it is

function won’t be proper function .

explanation from book p36*** amino acids substitution occurs in HBS chains >> a molecule of HBS contains

two normal alpha-globin chains and two mutant beta-globin chains ,in which glutamate at position six has

been replaced with valine . min 6.30

regions of a localizedements (conformations) in dimensional arrang-the ordered 3Secondary structure

polypeptide chain; not just peptide bond only there is additional bond which is H-bond.

- 3D structure in a space be as a-helix and b-pleated sheet.

-if there will be differentiate in structure shape ((ex. Alpha helix transform to beta helix)) >> lead to disease

لحوم في) prion protein) يسمى يروتين من بقايا وجود سببه الذي (mad cow disease) البقر جنون مرض الناتجه االمراض من***

تسمينها, اجل من االبقار اعالف مع وخلطها واالغنام االبقار المعاء طحن هو تواجده في تسبب والذي االبقار,

-so when prion protein arrive CNS to brain and caused spongiform encephalitis they discovered it could

transport to humans too which led to mad cow disease in humans

3

in sheep (Alpha protein transform to beta protein) >> lead to scrapie disease

*the both diseases where just transformation of Alpha protein to beta protein

Alzheimer’s diseaseAnd also in human bodies 9:15

Alpha protein transform to beta protein >>> levels of β-amyloid become elevated, and this protein

undergoes a conformational transformation from a soluble α helix–rich state to a state rich in β sheet and

prone to self-aggregation >>> so CNS which was dealing with alpha protein now will deal with beta protein

which lead to amyloid structures & blocks signals and stops commination 9:35

**note Alzheimer disease is different than dementia (انه بطل يجمع او يحكي عن عباره وهوه الخرف) , Alzheimer

disease fully stops communications or recognizing anything

because of destruction of massage and signal transportation and destruction of brain because protein

structure became different (was changed)

*can’t be healed

*nobody knows why protein changes

- not a genetically disease like sickle cell anemia

*autosomal recessive traits the genetic researcher can predict sickle cell anemia

*Alzheimer disease comes suddenly and can’t be predicted

-look slide 6

به االصابه الى ادى الذي البروتين في التغير يحدث لماذا معلوم وغير عالج له ليس الزهايمر مرض -

11:15

Alpha-helix slides 7+8 للصوره وتوضيح الحكي نفس

***-know that H-bounds parallel to the axis of alpha-helix

-h-bonds perpendicular on the axis of beta-helix

** Beta-Pleated Sheets are two types antiparallel or parallel.

In parallel >>> H-bounds are in angels but in antiparallel its perpendicular

*are compact

slides 9+10

13:40

Tertiary (3°) structure: the 3D arrangement in space of all atoms in a polypeptide chain Bonds stabilize

the 3° structure: Metal ion coordination, side chain H-bond, electrostatic attraction, disulfide bridges

between A.A, van der wal forces and hydrophobic interaction >> more bonds

Quaternary (4°) structure: the association of polypeptide chains.

- poly peptide chains separate and when collected together then get the function ,

each one as single unit has no function

- Quaternary (4°) structure has all previous bonds

*disulfide bridges between cysteines (cysteine + cysteine=cystine)

** Protein Classifications according to shape:

fibrous proteins && globular proteins

4

15:28

Slide 13 + 14 doctor just read them

*wool is alpha helix and has spaces

*silk is beta helix and compact

*because of that silk is warmer than wool

** Collagen: triple helix >>it’s alpha helix but consist of 3 polypeptides rather than one so it called rope

like structure 17:15

- Collagen is important because it found in tendons , C.T , bones , under the skin ,gums

- has small a.a like gly ((is found at almost every third residue )) to help in turns which can’t done

around large a.a . Also contain Proline (Pro) which makes up about 17% of collagen.

**Collagen contains two uncommon derivatives amino acids:

-Hydroxyproline (Hyp), derived from proline.

-Hydroxylysine (Hyl), derived from lysine (Lys)

- Depending on the type of collagen, varying numbers of hydroxylysines are glycosylated (mostly having

disaccharides attached).

-not directly inserted during translation (firstly translation (like a.a) then hydroxylation (a hydroxyl group

is added) and this step require vitamin C and copper as a cofactor.

- Cortisol stimulates degradation of (skin) collagen into amino acids.

- The best-known defect in collagen biosynthesis is Scurvy(leads to bleeding, fracture , gum bleeding) , a

result of a dietary deficiency of vitamin C required by prolyl and lysyl hydroxylases.

- The resulting deficit in the number of hydroxyproline and hydroxylysine residues undermines the

conformational stability of collagen fibers, leading to bleeding gums, swelling joints, poor wound healing,

and ultimately to death.

** Menkes’syndrome, characterized by kinky hair and growth retardation, reflects a dietary deficiency

of the copper required by lysyl oxidase, which catalyzes a key step in formation of the covalent cross-

links that strengthen collagen fibers.

20:25

Other disease resulting in Genetic disorders of collagen biosynthesis include: osteogenesis imperfecta,

characterized by fragile bones. In Ehlers-Dahlos syndrome, a group of connective tissue disorders that

involve impaired integrity of supporting structures, defects in the genes that encode α collagen-1,

procollagen N-peptidase, or lysyl hydroxylase result in mobile joints and skin abnormalities and elastic

skin .

-. In Ehlers-Dahlos syndrome joint movement become easier , loose links between vertebras >>> those

called “ rubber man “ البهلوانيه الحركات بيعملوا السيرك في بنشاهدهم يلي

21:50

Globular proteins: proteins which are folded to a more or less spherical shape

-ex. Myoglobin && hemoglobin

-they tend to be soluble in water and salt solutions

5

-most of their polar side chains are on the outside and interact with the aqueous environment by

hydrogen bonding and ion-dipole interactions

-most of their nonpolar side chains are buried inside

-nearly all have substantial sections of alpha-helix and beta-sheet

*tertiary and quaternary structures

*tertiary :myoglobin \ quaternary : hemoglobin

• Myoglobin: Function in O2 storage in muscles,

-a single continuous polypeptide chain of 153 amino acids.

-continuous 8 chains of alpha\beta helixes

-myo=muscle \ globin=protein part

*myopathy=defection\disease in muscles

-Compact with a single heme group in a hydrophobic pocket

-8 regions of - -sheet

- most polar side chains are on the surface

- nonpolar side chains are folded to the interior

-two Histidine side chains are in the interior, involved with interaction with the heme group.

**Heme: is a prosthetic group made from one protoporphyrin ring, and iron in the center

-protoporphyrin ring is made from 4 pyrrole rings

-Fe(II) of heme has 6 coordinate sites; 4 sites interact with N atoms of protoporphyrin((pyrrole rings)) , 1

with N of a His side chain, and 1 with either an O2 molecule or an N of the second His side chain (free site )

- Heme give the red color to hemoglobin , mitochondria,enzymes …etc

- Heme group around it goblin( polypeptide chains )

-the presence of iron in the protophyrin ring is what makes the heme

26:00

Heme >>> 4 pyrrole rings (protoporphyrin ) + fe

Fe (II) connect with>>> 4 (N atoms of protoporphyrin ) + 2 (either be free or connect with heme group )

carbon monoxide which is toxic because it’s affinity to attach (( CO2 or Oattach with * heme have affinity to

the last step in electron inhibits COwith heme group more than o2 affinity && in oxidative phosphorylation

transport system “cytochrome oxidase “ ))

with globin BUTO2 bind to CO = *25000 the affinity to bind to ithout globin ) has affinity to** free heme (w

it decreases affinity to *200\210

“ F globin chain “F8 >> it comes from TIDINE** HIS

- globin is 8 chains ( A , B , D , G , F, H … the doctor just mention 6 )

- In the absence of globin, Fe(II) has high affinity to CO while low affinity to O2 but In the presence of globin,

Fe(II) affinity to O2 increases and its affinity to CO decreases.

- In the absence of globin, Fe(II)(ferrous) can be easily oxidized to Fe(III)(ferric) which has no affinity to O2 .

O2من انه يتحد مع الهيم وبيسهل االتحاد مع CO (( بيجعل الزاويه اصعب على HIS E7* العالقه بين الغلوبين والهيم هي انه الغلوبين ))

6

بسهولة فبالتالي بيسهل االرتباط COبيمنع دخول // ارتباط E7HISالرتباط مع بعد امعه لكن COفبالتالي الهيم لوحده بيكون اسهل ارتباط

O2 مع

** HIS E7 act as a gate for binding of O2 or CO, so it facilitates the binding of O2 to Heme.

Back to slide 27

31:30

*lactate dehydrogenase is 4 units a has subunits found in cardiac muscles and some skeletal units and when

we make investigation for myocardial infarction we search for cardiac subunits

* The function of hemoglobin is to transport oxygen (also takes co2 to lungs from tissue).

: of (4 sub units)is a tetramer )Hb(nhemoglobi

- two alpha-chains (141 amino acids each)

and two beta-chains (153 amino acids each)

* each chain has 1 heme group>>> hemoglobin has 4 heme groups >> can bind up to 4 molecules of O2

(each heme to one oxygen molecule)

; when one O2 is bound, it becomes easier for the next O2 to bind (positive is cooperativebinding **

cooperativity )

) Hb (unloaded unoxygenatedHb (loaded) is different from that of oxygenatedthe structure of *

* it can be acidic or basic, oxygenated or unoxygenated

Buffer systemبالتالي بتكون جزء من

مالحظه : استذكر قصة دكتور مؤيد للجماعه يلي كانوا مروحين من االمتحان وبدهم يركبوا التاكسي وكيف كان التنافس على المقاعد ***

*hemoglobin can bind H+, CO2, Cl-, and 2,3-bisphosphoglycerate (BPG) which affect the ability of Hb to bind

and transport oxygen

** difference between hemoglobin && myoglobin :

myoglobin >> found in muscles >> tertiary structure >> one unit (alpha-unit ) of 153 a.a >> it has high affinity

for O2 >> hyperbolic ( fully saturated under very low pressure of O2 )>>takes only one oxygen molecule

hemoglobin >> found in blood >> Quaternary structure >> 4 subunit >> sigmoidal relationship(s shape) ( to

be saturated the concentration of O2 pressure must be increased

state (increasing pressure don’t increase saturating fully saturatedsaturated state >> arrive after **

\becomes plateau )

36:00

**Bohr effect << The effect of pH on the oxygen-binding ability of Hb .

*- as pH decreases (more acidic >> in metabolism & production of acids & production of 2,3-

diphosphoglycerate ), oxygen is released .

]+[H under 2Hb has lower affinity to O -*

HbO2 HbH++ H+ O2+

7

2from HbO 2promotes release of O 2CO -*

* H2CO3 is a weak acid >>> after dissociation >> H + HCO3

H + CO2 >> comes from metabolism

** in high altitude O2 pressure decrease >> called “hypoxia// anoxia “

anemiaبالتالي الجسم بحاجه انه يتعود على تركيز منخفض لالكسجبن ويلي ممكن يؤدي الى

فالرياضيين بيروحوا تخييم لما يكون عندهم مباراه في اماكن مرتفعه ليتعودوا على االنخفاض بتركيز االكسجين

*** look slide 34

42:00

bisphosphoglycerate )2.3 BPG (in blood is bound to Hemoglobin**

It comes from metabolism >> glycolysis >> from 1,3-BPG >>>

it Unites with beta-chains of HB with (LYS, ARG ) which promotes O2 dissociation

* Interaction is electrostatic, between negative charges on BPG and positive side chains

(e.g., Lys, Arg) of hemoglobin

** BPG promotes O2 dissociation

fully saturated >>> HB BPGwhen no **

>> HB become less saturated BPGwith * but*

43:30

**Fetal Hemoglobin, Hb F :

- mother ( maternal HB ) has 2,3-BPG but HbF don’t has 2,3-BPG ( because no metabolize in

muscles )

- the difference in degree of saturation between mother HB and fetal HB >>> lead to >> O2 flows

CO2 + H2 O

carbonicanhydrase

H2 CO3

H2 CO3 H+ + HCO3-

C

C

O-O

CH2 OPO32 -

OPO32 -H

2,3-Bisphosphoglycerate(BPG)

8

from maternal oxyhemoglobin to fetal deoxyhemoglobin (( fetal HB is less saturated withO2 but

maternal HB is fully saturated so maternal Hb gives fetal hb ))

-HBF has a higher affinity for O2 than maternal Hb A >>> so less affinity of O2 in HB A mean it

can release O2 .

-when the curve is to the left it means Hb has high O2 affinity

-when the curve is to the right it means Hb has lower O2 affinity which means it can release O2

just like enzyme to substrate relation which we will study later

-the target is to transport O2 so we need it to release and not to store it

Back to slide 39

notes:

*number of erythrocytes increase in high attitudes because hypoxia happens and the body

needs more oxygen so erythro biotin pump is stimulated to produce more RBCs

***blood doping : taking a rich with erythrocytes blood from a person and before an important

matches give it back to him so he have extra oxygen supply

*can’t be discovered

*blood can be good for 30 days\in hospitals they store it for 3 weeks then they return it to blood

bank

**Biomedical implications min 47

*Myoglobinuria

-uria=means in urine

-galactouria=galactose in urine \hyperglocuseria =high glucose in urine

*difference between uria and urea?

-UREA metabolic end product of protein

-URIA is related to urine

**myoglobinuria=myoglobin found in urine usually happens after crush injuries or muscle

damages

when infarction or injury happens myoglobin can’t reach muscles so it will be found in urine

**Anemia

-emia=blood

*galactosemia\leukemia\ *hyperglocusemia=high glucose in blood

Anemias=reductions in the number of red blood cells or of hemoglobin in the blood, can reflect

impaired synthesis of hemoglobin (eg, in iron deficiency(the most common anemia,

why??Because the most important source of iron is found in red meats and poor countries have

deficiency in meat); or impaired production of erythrocytes (eg, in folic acid or vit.B12 def.)

**HbA1C min 50

السكر التراكمي هيموغلوبين

-normally found 5% in normal humans if more then it means defect in controlling sugars

-RBCs live for 120 days so every two months you measure HbA1C

-HbA1C =glycosylation happens to normal Hb (added glucose)

مطلوبات ساليدات ما انشرحوا بس 4اخر**

удаче вceм ;p