Biohemija metabolizma (Školska 2019/2020.)
UVODNO PREDAVANJE
dr Milan Nikolić, docent
Metabolizam obuhvata sve hemijske procese koji se dešavaju u ćeliji.
Mali podsetnik...
• Metabolizam služi da:
~ obezbedi energiju, razgradnjom energijom bogatih nutrijenata ili korišćenjem sunčeve energije
~ molekule nutrijenata prevede u prekursore za izgradnju biomakromolekula i ćelijskih komponenti
~ obrazuje ili razgradi biomolekule za specijalizovane funkcije ćelije
Energija je sposobnost obavljanja rada.
Živi sistemi crpe, pretvaraju, skladište i koriste energiju.
Energija je neophodna za biosinteze, transport, kretanje, itd.
Metabolizam = Hemijske transformacije
Metabolički tipovi živih sistema
(a) Prema izvoru ugljenika:
• Autotrofi – redukcija CO2 iz vazduha
• Heterotrofi – iz organskih jedinjenja
(b) Prema izvoru energije:
• Fototrofi – transformacija svetlosne energije
• Hemotrofi – oksidacija hemijskih jedinjenja
- hemoorganotrofi oksiduju organska jedinjenja
- hemolitotrofi oksiduju neorganska jedinjenja
Jedinjenja bogata energijom
• Energija dobijena procesima oksidoredukcije mora biti
sačuvana za različite potrebe.
• Energija se u živim sistemima pre svega se konzervira
u obliku fosforilisanih jedinjenja.
1-5 mM
Jedinjenja neophodna za konzerviranje energije
Mehanizmi konzervacije energije kod hemoorganotrofa
Fermentacija - redoks proces
se odvija u odsustvu spoljnog
akceptora elektrona
Respiracija (disanje) - postoji spoljni akceptor elektrona
- aerobna - akceptor elektrona je molekulski kiseonik
- anaerobna - akceptor elektrona je neko drugo, obično
neorgansko jedinjenje
• ATP nastaje u toku katabolizma
organskog supstrata
• Sinteza ATP-a na račun proton-motorne sile koja nastaje u toku
prenosa elektrona kroz respiratorni lanac (oksidativna fosforilacija)
• Respiratorna goriva: rezultat regulisane digestije i
apsorpcije nutrijenata ili (selektivne) mobilizacije
rezervnih molekula
(hemorganotrofi)
omnivrous vs. herbivors
Metabolički profil životinjskih ćelija
Različita sposobnost ćelija i organa
za korišćenje metaboličkih goriva
Mozak: 100145 g Glc dnevno
Kalorijska homeostaza
Metabolička povezanost organa
Principi regulacije metabolizma
• Prostorna odeljenost metaboličkih puteva
(različita metabolička aktivnost & izmena metabolita
između citosola i mitohondrija)
• Metabolička specijalizacija organa
• "Pace-maker" reakcije
(kontrolne tačke metaboličkih puteva)
• Ograničavajući metaboliti
(Indikatori energetkog stanja ćelije)
• Regulacija aktivnosti enzima
(alosterna regulacija; inhibicija proizvodom; regulacija
povratnom spregom; regulacija količine enzima)
• Hormonska regulacija
Glavni tipovi metaboličkih enzima
Struktura nekih od najvažnijih metabolita
Predznanja neophodna za
uspešno pohađanje kursa
• Osnovi organske hemije
• Osnovi fizičke hemije
• Osnovi enzimologije
• Osnovi biologije
A functional group is a group of
atoms within a molecule that has a
characteristic chemical behavior.
Acids and Bases The vast majority of biological transformations are catalyzed by acids or bases.
Brønsted–Lowry Acids and Bases
Lewis Acids and Bases
A Lewis acid is a substance that accepts an electron pair from a base,
and a Lewis base is a substance that donates an electron pair to an acid.
Lewis acids are involved in a great many biological reactions, often as
cofactors (e.g. metal cations) in enzyme-catalyzed processes.
An acid is a substance that donates a proton (hydrogen ion, H+), and a base
is a substance that accepts a proton.
Electrophiles and Nucleophiles
An electrophile is a
“electron-loving” substance.
Electrophiles are either positively
charged or neutral and have a
positively polarized, electron-poor
atom that can accept an electron
pair from a nucleophile/base.
A nucleophile, by contrast, is
“nucleus-loving” substance.
Nucleophiles are either negatively
charged or neutral and have a lone
pair of electrons they can donate to
an electrophile/acid.
Mechanisms: Electrophilic Addition Reactions
Biological examples are the biosynthetic routes leading to steroids and other terpenoids.
The mechanism of the acid-catalyzed electrophilic
addition of water to 2-methylpropene.
Mechanisms: Nucleophilic Substitution Reactions
Mechanism of the SN2 reaction of
(S)-2-bromobutane with hydroxide ion
to yield (R)-2-butanol.
Mechanism of the SN1 reaction of
2-bromo-2-methylpropane with water
to yield 2-methyl-2-propanol.
An SN2 reaction is involved in biological
methylation reactions (-CH3 group is
transferred from S-adenosylmethionine
to various nucleophiles).
Nucleophilic Carbonyl Addition Reactions
Some typical nucleophilic addition reactions of aldehydes and ketones. (a) With a
hydride ion as nucleophile, protonation of the alkoxide intermediate leads to an
alcohol. (b) With an amine as nucleophile, proton transfer and loss of water leads to
an imine. (c) With an alcohol as nucleophile, proton transfer leads to a hemiacetal,
and further reaction with a second equivalent of alcohol leads to an acetal.
In biological pathways, NADH or NADPH is the most frequently used hydride-ion donor.
Conjugate (1,4) Nucleophilic Additions
Nucleophilic Acyl Substitution Reactions
Mechanism of the nucleophilic acyl substitution
reaction of OH- with methyl acetate to give acetate. The carboxypeptidase-catalyzed hydrolysis
of the C-terminal amide bond in proteins.
Occur frequently in biochemistry!
Mechanisms: Carbonyl Condensation Reactions
Mechanism of the Claisen condensation, a reversible,
base-catalyzed condensation reaction between two
molecules of ester to yield a β-keto ester.
Mechanism of the aldol reaction, a reversible, base-catalyzed
condensation reaction between two molecules of aldehyde or
ketone to yield a β-hydroxy carbonyl compound.
Mechanisms: Elimination Reactions
Examples of all three mechanisms occur in different
biological pathways, but the E1cB mechanism is particularly
common, and the substrate is usually an alcohol (X=OH).
The mechanisms of two of the more commonly occurring biological redox processes:
the oxidation of an alcohol (a) and the reduction of a carbonyl compound (b).
Oxidations and Reductions
(a)
(b)
NADH transfers a hydride ion to the carbonyl group in a nucleophilic
addition reaction, and the alkoxide intermediate is protonated.
Base B: abstracts the acidic -OH proton, the electrons from the -OH bond move to
form a C=O bond, and the hydrogen attached to carbon is transferred to NAD+.
Kako (na)učiti metaboličke puteve
• Nije memorisanje informacija, već razumevanje strategija
koje organizam koristi da bi ostvario određeni cilj.
• Razmatrati svaki metabolički put kroz sve složenije nivoe:
Nivo 1 – Svrha i lokalizacija;
Nivo 2 – Glavne faze;
Nivo 3 – Sudbina ugljeničnog skeleta;
Nivo 4 – Energetski bilans;
Nivo 5 – Posebne karakteristike i specifičnosti;
Nivo 6 – Kontrolne tačke;
Nivo 7 – Detalji (intermedijeri, reakcije, enzimi).
+ veze sa drugim metaboličkim putevima!!!
1. O svrsi metaboličkog puta može da se zaključi
iz njegove opšte jednačine
2. Glavne (pod)faze metaboličkog puta
3. Sudbina ugljeničnog skeleta
4. Energetski "ulaz" i "izlaz"
5. Specifičnosti metaboličkog puta
6. Kontrola metaboličkog puta • (Svi) metabolički putevi nisu aktivni u isto vreme
• Promene u aktivnosti ključnih metaboličkih enzima
7. Detalji metaboličkog puta