Biological Oxidation Flashcards
Stages of oxidation of foodstuffs
First stage :
Digestion in the git converts the macromolecules into small units. for eg. proteins are converted into amino acids. this is called primary metabolism
second stage :
- the products of digestion are absorbed, catabolised to smaller components and ultimately oxidised to co2.
- the reducing equivalents are mainly generated in the mitochondria by the final common oxidative pathway, citric acid cycle.
- in this process, NADH and FADH2 are generated.
- this is called secondary or intermediary metabolism
third stage :
- these reduced equivalents (nadh, fadh2) enter into the ETC or respiratory chain where energy is released.
- this is tertiary metabolism or internal respiration or cellular respiration.
ATP hydrolysis importance.
- hydrolysis of ATP to ADP provides the energy to perform work.
- ATP - ADP cycle is the fundamental mode of energy transfer in biologic systems
- atp is an energy rich compound because its triphosphate unit contains two phosphoanhydride bonds. the amount of energy available from hydrolysis of atp under standard conditions which can be utilised for energy requiring processes in the body is defined as the monetary value of the atp currency. it is equal to -7.3 kcal/mol
- energy released is more when atp us hydrolyzed to amp and ppi since the pyrophosphate is immediately hydrolyzed to 2pi
- atp hydrolysis is used to provide energy for anabolic pathways during synthesis of glycogen, proteins, nucleic acids and fatty acids.
- atp is also utilised for detoxification processes like conversion of ammonia to urea.
- this atp expenditure by the cells is essential to provide an overall negative ∆g° for the anabolic processes to be driven forward. otherwise the precursors would accumulate within the cells
redox potential, oxidation, reduction and redox couple
redox potential of a system is the electron transfer potential
oxidation is defined as the loss of electrons and reduction as the gain in electrons
when a substance exists both in the reduced state and in the oxidised state the pair is called a redox couple.
negative and positive redox potentials
when a substance has lower affinity for electrons than hydrogen, it has a negative redox potential.
- h+»>e- — negative
- h+«
substrate level phosphorylation
here energy from a high energy compound is directly transferred to nucleoside diphosphate to form a triphosphate without the help of etc
- biphosphoglycerate kinase
- pyruvate kinase
- succinate thiokinase
- atp generation is coupled with a more exergonic metabolic reaction
- the hydrolysis of a thioester bond is slightly more exergonic than atp hydrolysis. the cleavage of the thioester bond in succinyl coa brings about the synthesis of one molecule of gtp from gdp by substrate level phosphorylation.
what is biological Oxidation
the transfer of electrons from the reduced coenzymes through the respiratory chain to oxygen js known as biological Oxidation.
- energy released during this process is trapped as atp
this coupling of oxidation with phosphorylation is called ______
oxidative phosphorylation
in the body oxidation is carried out by
- successive dehydrogenations
enzymes involved in biological Oxidation
- all enzymes involved belong to the major class of oxidoreductases
1) oxidases : these enzymes catalyze the removal of h from substrates but only oxygen can act as acceptor of hydrogen so that water is formed
AH2 + 1/2 O2 —-> A + h2o
eg- cytochrome oxidase, tyrosinase, polyphenol oxidase, catechol oxidase and monoamine oxidase.
2) aerobic dehydrogenases
- catalyze the removal of h from a substrate but oxygen can act as an acceptor.
- these enzymes are flavoproteins and the product is usually hydrogen peroxide
AH2 + O2 —-> A + H2O2
- flavoproteins contain either FMN or FAD as prosthetic group.
eg - L amino acid oxidase
- xanthine oxidase
3) Anaerobic dehydrogenases : catalyze the removal of h from a substrate but oxygen cannot act as the h acceptor. (coenzymes do) thus when the substrate is oxidised the coenzyme is reduced
- NAD+ linked dehydrogenases - derived from nicotinic acid.
H2 —-> h + h+ + e-
AH2 + NAD+ —–> NADH + H+
eg-
- glyceraldehyde 3 phosphate dehydrogenase
- malate dehydrogenase
- glutamate dehydrogenase
- pyruvate dehydrogenase
NADP+ linked dehydrogenase : take part in reductive biosynthetic reactions like fatty acids synthesis and cholesterol synthesis
- eg - glucose 6 phosphate dehydrogenase
FAD linked dehydrogenase: both hydrogens attach to the flavin ring eg - - succinate dehydrogenase - fatty acyl coa - dehydrogenase - glycerol phosphate dehydrogenase
cytochromes : all the cyt except cytochrome oxidase are anaerobic dehydrogenases.
- hemo proteins having an iron atom.
cyt b, c1 and c are in mitochondria
cyt p450, b5 in endoplasmic reticulum
4) hydroperoxidases
- peroxidase: remove free radicals like hydrogen peroxide
H2O2+ AH2 –peroxidase—> 2h2o + A
eg- glutathione peroxidase in rbcs, leukocyte peroxidase and horse radish peroxidase
catalase : hemoproteins.
2h2o2 —-catalase—–> 2h2o2 + o2
5) oxygenases
• mono oxygenases : aka mixed function oxidases.
- one oxygen atom incorporated into the substrate while the other is reduced to water. aka hydroxylases because oh group is incorporated into the substrate
A-H + O2 + BH2 —-hydroxylase—> A-OH + H2O + B
- phenylalanine hydroxylase
- tyrosine hydroxylase
- cytochrome p450
• dioxygenases : both the oxygen atoms are incorporated into the substrate compound
- tryptophan pyrrolase
- homogentisic acid oxidase
high energy compounds
- these compounds when hydrolyzed will release a large amount lf energy that is they have a large ∆G°
- the free energy of hydrolysis of an ordinary bond varies from -1 to -6 kcal/mol. on the other hand, the free energy of high energy bonds varies from -7 to -15 kcal/mol.
- defined by the ∆G° of atp
phosphate compounds
- nucelotides (atp, gtp, utp, udp, glucose)
- atp to amp + ppi
- atp to adp + pi - creatine phosphate
- arginine phosphate
- 1,3 bisphospho glycerate
- phosphenol pyruvate
- carbamoyl phosphate
sulphur compounds
- coa derivatives
- acetyl coa
- succinyl coa
- fatty acyl coa
- hmg coa - s adenosyl methionine (SAM)
ATP
- atp is the universal currency of energy within the living cells
- the hydrolysis of atp to adp udner standard conditions releases -30.5 kj/mol or -7.3 kcal/mol
- the energy in the atp is used to drive all endergonic (biosynthetic) reactions.
- at rest, na+-k+-atpase uses up one third of all atp formed.
- other energy requiring processes arr biosynthesis of macromolecules, muscle contractions, cellular motion etc.
- atp us continually being hydrolyzed and regenerated
- an average person at rest consumes and regenerated atp at a rate of approximately 3 molecules per second i.e about 1.5 kg /day.
creatine phosphate
- phosphocreatine (creatine phosphate or cp) provides a high energy reservoir of atp to regenerate atp rapidly by the lohmanns reaction catalzed by creatine phosphate
- ATP + Creatine —-> Phosphocreatine+ ADP + ∆G° (-10.5 kcal/mol)
- the reaction is mitochondrial and is of special significance in the myocardium which has a hugh energy requirement
- energy transfer to the heart’s myofibrils is by creatine kinase energy shuttle
- cp is a smaller molecule than atp and can rapidly diffuse from the myocardium to the myofibrils
- storage forms of high energy phosphates such as cp and arginine phosphate are called phosphagens
- cp mainly seen in skeletal muscle, heart and brain.
ETC
Characteristics;
- functions inside the mitochondria and located in the inner mitochondrial membrane
- the inner mitochondrial membrane is highly selective in its permeability
- the electrons flow from electronegative potential (-0.32) to electropositive potential (+0.82)
- there are four distinct multiprotein complexes — complex I, II, III, IV.
- these are interconnected by two mobile carriers — coenzyme Q and cytochrome c
- protein complexes are arranged in the order of increasing reduction potentials.
ETC — complexes
complex I
- aka NADH-CoQ reductase or Nadh dehydrogenase complex
- tightly bound to the inner mitochondrial membrane
- contains a flavoprotein (Fp) consisting of FMN as prosthetic group and as iron sulphur - protein ( Fe-S)
- two electrons and one hydrogen ion are transferred from nadh to the flavin prosthetic group of the enzyme
NADH + H+ + FMN —–> FMNH2 + NAD+
- the electrons from fmnh2 are then transferred to fe-s. the electrons are then transferred to coenzyme Q (ubiquinone) (coQ)
- overall function of this complex is to collect pair of electrons from Nadh and pass them to coq.
- the energy released is 12 kcal/mol. this is utilised to drive 4 protons out of the mitochondria
complex II or Succinate - Q - Reductase
- the electrons from FADH2 enter the etc at the level of coenzyme Q.
- this step does not liberate enough energy to act as proton pump.
- the three major enzyme systems that transfer their electrons directly to ubiquinone from FAD prosthetic group are:
1) succinate dehydrogenase
2) fatty acyl coa dehydrogenase
3) mitochondrial glycerol phosphate dehydrogenase
complex III or cytochrome reductase
- this is a cluster of iron sulphur proteins, cytochrome b and c1 both contain heme prosthetic group.
- iron in heme group shuttles between fe3+ and fe2+ forms.
- the free energy change is -10kcal/mol and 4 protons are pumped out
complex IV or cytochrome oxidase
- it contains different proteins including cytochrome a and cytochrome a3
- 4 electrons are accepted from cytochrome c and passed onto molecular oxygen
- during this, 2 h+ are pumped out
complex V or atp synthase
- it is a protein assembly in the inner mitochondrial membrane.
- proton pumping atp synthase (otherwise called fo-f1 atpase) is a multisubunit transmembrane protein.
- two functional units named f1 and f0.
- fo unit - o stands for oligomycin as fo us inhibited by oligomycin (serves as a proton channel through with protons enter into mitochondria)
- f1 unit - projects into the matrix.
catalyzes the atp synthesis. atp synthesis requires mg2+ ions.
f1 has 3 conformation states for the alpha-beta functional unit.
o state - does not bind substrate or products. catalytically inactive
L state- loose binding of substrate and products. catalytically sluggish
t state - tight binding of substrate and products. catalytically active
malate aspartate shuttle
- mitochondrial membrane is impermeable to nadh.
- the nadh equivalents generated in glycolysis are therefore to be transported from cytoplasm to mitochondria for oxidation.
- this is achieved by the malate aspartate shuttle or the malate shuttle
- it operates mainly in liver, kidney and heart
- enzymes involved - malate dehydrogenase (mdh) and aspartate amino transferase.
- from one molecule of nadh in the mitochondria 2.5 atp molecules are generated
