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LEHNINGER

PRINCIPLES OF BIOCHEMISTRY

5th Edition

David L. Nelson and Michael M. Cox

©

2008 West. H. Freeman and Company

CHAPTER 19

Oxidative Phosphorylation

Cellul

Cellul æ

ær

r

respirasjon

respirasjon :

: siste

siste

trinn

trinn

Elektronoverføring

og

oksidativ

fosforylering

Oksidativ

fosforylering

Oksidativ

Oksidativ

fosforylering

fosforylering

syntese

av

ATP fra

ADP og

Pi

oksidasjon

av

NADH og

FADH2 generert

fra

oksidering

av

brenselsmolekyler

Mitokondrier

Mitokondrier

To

membraner

Ytre

membran:

permeabel

for små

molekyler

Indre

membran:

ikke

permeabel

for de fleste

molekyler

og

ioner

rommer

elektron-send kjedens

komponenter

og

ATP synthase

Matrix

inneholder:

-PDH kompleks

-CAC enzymer

-β-oksidasjon

enzymer

+++

B

Bæ

ærere av elektroner

rere av elektroner

NADH, NADPH, FADH2

og FMNH2

Dehydrogenaser i katabolske pathways overfører e -

til NAD+

og

NADP+

Flavoproteiner har FAD el. FMN som prostetisk gruppe,

aksepterer også

eastward-

fra katabolske pathways

Ubiquinone (Q)

Calorie-free, fettløselig molekyl i indre mitokondrielle membran

Cytochromer

Proteiner med prostetisk heme gruppe

Jern-svovel proteiner

Proteiner med jern-svovel sentre

Prostetiske

Prostetiske

grupper

grupper

p

på

å

cytochromer

cytochromer

Jern

Jern -

-svovel sentre p

svovel sentre p å

å

jern

jern -

-svovel proteiner

svovel proteiner

Fe-S senter 2Fe-2S senter 4Fe-4S senter

Elektrontransportkjeden

Elektrontransportkjeden

Elektrontransportkjedens

proteiner

pumper protoner

ut

av

den mitokondrielle

matrix mens

elektroner

strømmer

fra

FADH2

og

NADH til

O2

Kompleks

Kompleks

I (NADH

I (NADH dehydrogenase

dehydrogenase )

)

Katalyserer ii koblede prosesser:

1)

Overføring av hydrid ion (1H+

+ 2e - ) fra NADH og 1H+

fra

matrix til Q

2)

Overføring av 4H+

fra matrix

til intermembran rommet

Protonpumpen drives av

elektronoverføring

Reaksjonen er vektoriell: flytter

protoner i en spesifikk retning

Netto likning:

NADH + 5HNorth+

+ Q NAD+

+ QHii

+ 4HP+

Kompleks I overf

Kompleks I overf ø

ører

rer eastward

e-

-

til Q

til Q

Q (ubiquinone)

Q (ubiquinone)

Også

kalt coenzym Q

Benzoquinone med

isoprenoid sidekjede

Kan akseptere e -

for å

danne

semiquinone radikal eller 2e-

for å

danne ubiquinol

Overf

Overf ø

øring

band

av

av

elektroner

elektroner

til

til

ubiquinone

ubiquinone

(Q)

(Q)

Q kan motta e -

fra:

i)

NADH (Kompleks I)

ii)

Succinat (Kompleks Two, CAC)

three)

Fatty acyl-CoA (Acyl-CoA

dehydrogenase (β -

oksidasjon)

overfører e -

via

ETF og ETF:Q

oksidoreduktase)

4)

Glycerol 3-fosfat (direkte fra

glycerol three-fosfat

dehydrogenase)

Q overf

Q overf ø

ører

rer e

e-

-

til Kompleks 3

til Kompleks Three

Cytochrome

Cytochrome

bc

bcane

1

kompleks

kompleks

(Kompleks

(Kompleks

III)

Three)

Katalyserer koblede prosesser:

1)

Overføring av e -

fra QH2

til

Cyt c

ii)

Overføring av H+

fra matrix

til intermembran rommet

Dimer: 2 monomerer

Q

Q

syklusen

syklusen

Netto likning:

QH2

+ two cyt c

(oksidert) + 2HN+

Q + 2 cyt c

(redusert) + 4HP+

Cyt C overf

Cyt C overf ø

ører

rer e

e-

-

til Kompleks Four

til Kompleks IV

Cytochrome

Cytochrome

c

c (Cyt

(Cyt c

c)

)

Løselig protein i intermembran rommet

En prostetisk gruppe: heme

Aksepterer et east-

av gangen fra Kompleks III

Overfører e-

til Kompleks IV

Beveger seg mellom Kompleks 3 og

Kompleks IV for å

akseptere og avlevere

elektroner

Cytochrome

Cytochrome

oksidase

oksidase

(Kompleks

(Kompleks

Iv)

Iv)

Aksepterer e -

fra Cyt c

Katalyserer reduksjon av O2

:

4e -

overført fra Cyt c

4H+

fra matrix

danner 2Htwo

O

Reduksjonen av O2

er koblet med

overføring av 4H+

fra matrix til

intermembran rommet

Netto likning:

four cyt c

(redusert) + 8HN+

+ O2

4 cyt c

(oksidert) + 4HP+

+ 2Hii

O

Str

Str ø

øm

thousand

av

av

elektroner

elektroner

og

og

protoner

protoner

Netto

vektoriell

likning:

NADH + 11HDue north+

+ ½

Otwo

NAD+

+ 10HP+

+ Htwo

0

Netto reaksjon: ½

O2

+ 2H+

+ 2e -

Htwo

O

Elektrontransportkjeden:

Elektrontransportkjeden:

oppsummering

oppsummering

ETC består

av

4 komplekser

(I-4) og

to

mobile elementer

(Q og

cyt

c) som befinner seg i den

indre

mitokondrielle

membranen/intermembran rommet.

Elektroner og

protoner

overføres

fra

Kompleks

I og

II til

Q. Kompleks

I pumper

four H+

over membranen

for hver

2e -

overført

til

Q.

2e-

overføres

fra

QH2

til

Kompleks

Iii gjennom

Q syklusen.

Kompleks

Iii overfører sekvensielt

4east-

til

Cyt

c

og

pumper

2H+

over

membranen

for hvert

e-

overført til

cyt

c.

Cyt

c

forflytter seg

til

Kompleks

Four og

overfører

et

elektron

til

Kompleks

IV

(x4)

Kompleks

4 katalyserer

en

ive -

reduksjon

av

O2

, konsumerer

4H+

og

danner

dermed 2H2

O, mens

4H+

simultant pumpes over

membranen.

Netto reaksjon: ½

O2

+ 2H+

+ 2e-

Htwo

O

The

The proton

proton -

-motive

motive

force

force

Den indre

membranen

separerer

matrix

(North side) fra intermembran

rommet

(P

side)

Pumping av

H+

av

ETC kompleksene

skaper

en forskjell i

[H+ ] på

N

og

P side

Forskjellen

i

kjemisk

konsentrasjon

( pH) og

fordelingen av ladninger

(ψ )

skaper

en proton-drivkraft (proton-motive

force)

( Thou)

Den

Den

kjemiosmotiske

kjemiosmotiske

modellen

modellen

ATP

ATP synthase

synthase

2 funksjonelle

domener:

Fo

og

Fi

Fo

: integrert

i

membranen

F1

: festet

til

Fo

Syntetiserer

ATP fra

ADP og

Pi

Fone

Fo

ATP synthase

ATP

ATP synthase

synthase

Fo

har

en

proton pore

Strøm

av

protoner

gjennom

poren

får

F1

til å

rotere

Fone

har

iii α

subenheter

og

3 β

subenheter

som er organisert

rundt

"skaftet"

γ

β

subenhetene

har

bindingsseter

for

ATP/ADP

ATP/ADP-binding

og

ATP syntese er

kontrollert

av

konformasjonsendringer

indusert

av

rotasjonen

om

γ

Proton

Proton-

-drivkraften driver frigj

drivkraften driver frigj ø

øringen av ATP fra enzymet

ringen av ATP fra enzymet

Frigjøringen av ATP fra enzymet er energibarrieren, ikke ATP

syntesen

Rotasjonskatalyse

Rotasjonskatalyse

3 forskjellige konformasjoner

for β

subenhetene:

-

β-ATP (tett bounden)

-

β-ADP (løs binding)

-

β-empty (svært løs binding)

Hver β

subenhet endres

mellom alle 3 konformasjoner i

løpet av hver rotasjon

En komplett rotasjon:

-

9 H+

overført fra intermembran

rommet til matrix

-3 ATP produsert

ATP

ATP synthase

synthase :

: oppsummering

oppsummering

Proton-motive force driver ATP syntesen gjennom ATP synthase

ATP synthase utfører "rotasjonssyntese": protoner strømmer

gjennom Fo

og får dermed Fi

til å

rotere. Dette gir

konformasjonsendringer i ATP/ADP-bindingssetene

Dannelse av ATP på

enzymet krever light energi, proton-

drivkraften frigjør ATP fra bindingssetene

For hver ATP produsert, strømmer 3H+

fra intermembran rommet

til matrix

Oversikt

Oversikt

over

over

oksidativ

oksidativ

fosforylering

fosforylering

Transportprosesser

Transportprosesser

over

over

den

den

mitokondrielle

mitokondrielle

indre

indre

membranen

membranen

1)

ATP/ADP send

2)

Ship

av

NADH

2a) Malat-aspartat skyttel (lever, nyrer, hjerte)

2b) Glycerol 3-fosfat skyttel (skjelettmuskler, hjerne)

ATP/ADP transport

ATP/ADP transport

Malat

Malat -

-aspartat skyttel

aspartat skyttel

Glycerol 3

Glycerol 3 -

-fosfat skyttel

fosfat skyttel

Regulering av de ATP

Regulering av de ATP -

-produserende pathways

produserende pathways

Sammenkoblet regulering av:

-

Glykolysen

-

Sitronsyresyklusen

-

Oksidativ fosforylering

Kontroll ved:

-

[ATP]

-

[ADP]

-

[AMP]

-

[NADH]

Kap

Kap

19:

19: Oksidativ

Oksidativ

fosforylering

fosforylering -

-

hva er viktig?

hva er viktig?

Elektrontransportkjeden:

de

forskjellige

komponentene

og

deres

rolle,

strømmen

av

elektroner

og

protoner,

netto

reaksjon

Proton-drivkraften (proton-motive forcefulness)

Den kjemiosmotiske modellen

Syntese

av

ATP ved

ATP synthase: struktur

og

hvordan

enzymet

opererer

Transportprosesser

over den

mitokondrielle

indre

membranen:

ATP/ADP

transport, malat-aspartat

skyttel

og

glycerol

3-fosfat

skyttel

... Although uniform with full general 3D object data, these models mainly focus on the overall poly peptide topology but overlook the subtleties in the fine-grained geometries, which could be essential in many scenarios. For case, given an amino acrid characterized by its backbone atoms (carbon, nitrogen, and oxygen) and a side-concatenation, as shown in Figure ane, the locations of the backbone atoms determine the poly peptide skeleton locally and its local frame orientation affects how it interacts with other amino acids, either of which tin can take important impacts on the unabridged protein structure (Nelson et al., 2008). It is also well-known that a small change to the side chain angles could cause a significant change to the protein functionality, especially when it interacts with other biological molecules (Jacobson et al., 2002;Misiura et al., 2021). ...

... A more concrete application in the experiment section demonstrates how VNN-based models are limited in perceiving angles (e.grand. side-chain torsion angles), which have been proven crucial for proteins to collaborate with other partners through not-covalent bonds (Nelson et al., 2008). ...

  • Jiahan Li
  • Shitong Luo
  • Congyue Deng
  • Jianzhu Ma

A protein performs biological functions by folding to a particular 3D construction. To accurately model the protein structures, both the overall geometric topology and local fine-grained relations between amino acids (e.g. side-chain torsion angles and inter-amino-acrid orientations) should be carefully considered. In this piece of work, we advise the Directed Weight Neural Network for better capturing geometric relations amid different amino acids. Extending a single weight from a scalar to a 3D directed vector, our new framework supports a rich ready of geometric operations on both classical and SO(iii)--representation features, on top of which we construct a perceptron unit for processing amino-acid information. In addition, we introduce an equivariant message passing image on proteins for plugging the directed weight perceptrons into existing Graph Neural Networks, showing superior versatility in maintaining SO(3)-equivariance at the global scale. Experiments evidence that our network has remarkably ameliorate expressiveness in representing geometric relations in comparison to classical neural networks and the (globally) equivariant networks. It besides achieves state-of-the-fine art performance on various computational biology applications related to protein 3D structures.

... lining the bronchioles; their overproduction is a major cause of inflammation in asthma and allergic rhinitis (Nelson et al., 2008). Leukotriene antagonists are used to treat these disorders past inhibiting the production or activity of leukotrienes (Scott and Peters-Golden, 2018). ...

  • Ndiokwere Akaolisa Obumnaeme
  • Johnkennedy Nnodim Johnkennedy Nnodim

Inflammation is the complex pathophysiologic response of tissue injury or infection. Biochemical mediators released during inflammation intensify and propagate the inflammatory response leading to organ dysfunction and major problem in many clinical conditions such as sepsis, severe burns, acute pan-creatitis, hemorrhagic daze, and trauma. Inflammatory mediators are soluble, diffusible molecules that act systemically and locally at the site of injury or infection. Inflammation causes stimulation of body's defense system; activation of leukocytes causes release of inflammatory mediators at a site of infection or inflammation which control the later accumulation and activation of other cells. These mediators are produced past the body cells; histamine, prostanoids, cytokines secreted primarily from neutrophils, monocytes, macrophages, platelets, mast cells, endothelial cells lining the blood vessels, damaged tissue cells or from blood plasma derived; Contact system/Coagulation cascade (Hageman factor (clotting factor XII)), Kinin generation, Complement system. Medical laboratory qualitative and quantitative analysis of these inflammatory mediators in conjunction with other inflammatory markers play a very vital part in the medical laboratory diagnosis of both chronic and acute inflammation and inflammatory dis

... Among lipids, triglycerides are by far the most abundant class of lipids in the human body, making up the bulk of the then-called "body fat" [4]. They are as well the master lipids in food, including vegetable oils [v]. Membrane lipids, mainly phospholipids and cholesterol, institute a small fraction of the human being body lipids. ...

This work intends to describe the physical properties of red blood jail cell (RBC) membranes in obese adults. The hypothesis driving this research is that obesity, in addition to increasing the amount of body fat, volition also modify the lipid limerick of membranes in cells other than adipocytes. Forty-nine control volunteers (16 male person, 33 female person, BMI 21.8 ± 5.6 and 21.v ±4.2 kg/m2, respectively) and 52 obese subjects (16 male and 36 female, BMI 38.2±11.0 and 40.vii±8.7 kg/m2, respectively) were examined. The two physical techniques applied were atomic forcefulness microscopy (AFM) in the strength spectroscopy mode, which allows the micromechanical measurement of penetration forces, and fluorescence anisotropy of trimethylammonium diphenylhexatriene (TMA-DPH), which provides data on lipid guild at the membrane polar–nonpolar interface. These techniques, in combination with lipidomic studies, revealed a decreased rigidity in the interfacial region of the RBC membranes of obese as compared to control patients, related to parallel changes in lipid composition. Lipidomic data show an increase in the cholesterol/phospholipid mole ratio and a decrease in sphingomyelin contents in obese membranes. ω-three fatty acids (e.g., docosahexaenoic acid) appear to be less prevalent in obese patient RBCs, and this is the instance for both the global fatty acid distribution and for the individual major lipids in the membrane phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). Moreover, some ω-vi fatty acids (e.m., arachidonic acrid) are increased in obese patient RBCs. The switch from ω-3 to ω-6 lipids in obese subjects could be a major factor explaining the higher interfacial fluidity in obese patient RBC membranes.

... The above phenomena shown in Fig 4 can exist explained from the theoretical analysis, for which we consider the Gibbs complimentary energy variation at the starting moment ΔG. For this cotransport process of the E. coli LacY protein, we can rewrite the free energy variation in terms of the sum of the chemic potential multiplying the stoichiometry of the two particles [21], bringing the data and slightly transforming and then nosotros have, ...

  • Haoran Sun

The symport of lactose and H ⁺ is an of import physiological process in E . coli , for information technology is closely related to cellular energy supply. In this paper, nosotros review, extend and analyse a newly proposed cotransport model that takes the "leakage" phenomenon (uncoupled particle translocation) into account and as well satisfies the static head equilibrium condition. Then, we use the model to report the equilibrium properties, including equilibrium solution and the fourth dimension required to reach equilibrium, of the symport process of E . coli LacY poly peptide, when varying the parameters of the initial country of cotransport system. It tin can be found that in our extended model, H ⁺ and lactose volition reach their equilibrium country separately, and when "leakage" exists, information technology linearly affects the equilibrium solution, which is a useful property that the original model does not have. We subsequently investigated the effect of the volume of periplasm and cytoplasm on the equilibrium properties. For a sure East . coli jail cell, as it continues to lose water and contract, the time for cytoplasm pH to be stabilized by symport increases monotonically when the prison cell survives. Finally, nosotros reproduce the experimental data from a literature to verify the validity of the extension in this symport procedure. The above phenomena and other findings in this paper may help us to not only further validate or improve the model, just likewise deepen our agreement of the cotransport process of East . coli LacY protein.

  • Pedro Martinez-Gomez Pedro Martinez-Gomez

En esta tesis doctoral se atiende a la naturaleza y alcance de los avances recientes en la Posgenómica, empleando como herramienta el realismo experimental defendido por Ian Hacking. Con este fin, desarrollamos una triple tarea. En primer lugar, ofrecemos un análisis de la Genética y del concepto de gen desde sus orígenes a comienzos del siglo XX hasta la presente etapa Posgenómica desde una perspectiva experimentalista. En segundo lugar, resumimos las implicaciones epistemológicas derivadas de este análisis experimentalista de la Posgenómica en relación con nuestro conocimiento acerca de la realidad de la Genética y las aproximaciones para conocer esta realidad. Finalmente, exploramos las implicaciones ontológicas derivadas de este análisis en relación con la esencia de la realidad genética y la herencia de caracteres y la esencia del concepto de gen como responsable de esta herencia.

  • Juliet Veskova
  • Federica Sbordone
  • Hendrik Frisch

The development of sustainable plastic materials volition exist flanked with conscious resource management, waste recovery frameworks, and social change. Nonetheless, developing strategies toward controlled polymer degradation remains a primal challenge—whether as a failsafe mechanism for materials that escape the resources recovery cycle, or where distinct degradation pathways are required for specific applications such equally in the biomedical realm. This perspective highlights recent trends, challenges, and future strategies on three levels: 1) On the materials level, by the incorporation of enzymes into polymer materials that catalyze polymer deposition under benign conditions; 2) On the domain level, crystalline segments of polymer materials are ofttimes inert, fifty-fifty to enzymatically catalyzed deposition. Gaining an understanding of the mode of interaction betwixt enzymes and polymer chains is key to controlling degradation of all polymer morphologies within materials. Processive depolymerization mechanisms, where the enzyme binds polymer chain ends and depolymerizes along the concatenation are extremely promising for efficient polymer degradation; iii) On the molecular level, where polyesters exhibit enzymatic targets of ester bonds through their polymer backbone, poly(alkene)due south c of all carbon backbones. To enable degradation of this most abundant course of polymers, strategies must exist developed to incorporate enzymatic targets into the courage. Polymer degradation is a key challenge that can merely be solved by a joint effort of governance, personal behavior, and physical sciences. This perspective highlights recent strategies in the field of polymer chemistry that tackle controlled polymer degradation from the level of chemic bonds all the mode into plastic materials.

  • Etinosa C. Osemwota
  • Adeola M. Alashi
  • Rotimi Aluko Rotimi Aluko

Defatted lentil seed flour proteins were separated into their constituent albumin (ALB), globulin (GLB) and glutelin (GLT) fractions followed by determination of their structural and functional properties. The GLB fraction demonstrated superior solubility (84%–100%) at acidic and alkaline pH values when compared to the lower values for ALB and GLT. Amino acid composition assay showed lower contents of hydrophobic and sulphur‐containing residues for GLB. Even so, GLB had the highest in vitro protein digestibility, which may exist due to lower contents of rigid secondary construction fractions like the β‐sheet and β‐turns. In contrast, water and oil property capacities likewise as gelling ability were amend for GLT and ALB than GLB. The GLT fraction formed very poor emulsions at pH iii and 5 but emulsification was significantly (p < 0.05) improved (smaller oil droplets) at pH 7 and 9. Foaming capacity was strongest for GLB, especially at pH 5, vii and 9 where increase in protein concentration had a negative effect on foam formation. Overall, the protein type and pH of the surround had stronger effects on emulsion and foaming properties than the protein concentration. Dark-green lentil seed proteins were sequentially separated into albumin, globulin, and glutelin fractions based on their solubility in h2o, NaCl solution and NaOH solution, respectively. Glutelin and globulin constituted the major protein fractions while albumin was present as a small-scale fraction. Structural and functional properties of the protein fractions were highly influenced by pH of the surround.

  • A. A. Shcherbatykh
  • M. S. Chernov'yants
  • L. D. Popov

A promising area in the analytical chemical science of thiol-containing compounds is the apply of heterocyclic disulfides as analytical agents, but at present simply a few of them are widely used. In this paper, we evaluate the possibility of using three different heterocyclic disulfides 2,ii′-dithiobis[v-phenyl-1,3,4-oxadiazole] (I), 2,two′-dithiobis[benzoxazole] (2) and 8,8′-dithiobis-quinoline (III) every bit analytical reagents for the depression-mass aminothiols cysteine and glutathione conclusion. The optimal analysis conditions were found. Spectrophotometric, kinetic, CE, and HPLC methods using I, II, III for the determination of cysteine and glutathione were developed. The obtained methods are characterized by accurateness and sensitivity (detection limits in the range of x–5–ten–6 1000) sufficient to quantify cysteine and glutathione in their physiological concentrations. Finally, the proposed disulfides were used to determine the SH-content in the bovine serum albumin (BSA). Considering a number of criteria (applicative pH range, absorption backdrop, susceptibility to hydrolysis) it was ended that the proposed reagents have advantages over the commonly used ones (such every bit the Ellman reagent).

This work reviews the use of carbohydrates and their derivatives as renewable raw materials in the production of surfactants. Methods to attain state‐of‐the‐fine art carbohydrate‐derived surfactants are described. This includes surfactants widely used present and others that have not however transcended across the academic field. Given the abundance of hydroxyl groups in carbohydrates and the considerable quantity of different surfactant structures that tin can be generated during their synthesis, selectively obtaining a target product represents a claiming. Therefore, this work focuses on the platform chemicals available to synthesize biobased surfactants. The starting time part of the review comprises a cursory introduction of simple and circuitous carbohydrates to ameliorate understand their chemical science. Then, a description of the processes to obtain biobased building blocks derived from carbohydrates according to the National Renewable Energy Laboratory (NREL, USA), and their usefulness in synthesizing surfactants is presented. This provides an organized inventory of the cognition around the synthesis–production of surfactants from carbohydrate derivatives, emphasizing raw materials that could be inserted into the round bioeconomy concept. Finally, the current industry trends and the potential role of biobased surfactants around new dioxane regulations are discussed. Open up access link: https://aocs.onlinelibrary.wiley.com/share/KFHIXIR2YNANWCNARMNQ?target=10.1002/jsde.12581

  • Andreas Mayer Andreas Mayer

Membrane fusion is a fundamental biochemical reaction and the last step in all vesicular trafficking events. It is crucial for the transfer of proteins and lipids between dissimilar compartments and for exo- and endocytic traffic of signaling molecules and receptors. Information technology leads to the reconstruction of organelles such as the Golgi or the nuclear envelope, which disuse into fragments during mitosis. Hence, controlled membrane fusion reactions are indispensible for the compartmental organisation of eukaryotic cells; for their advice with the environment via hormones, neurotransmitters, growth factors, and receptors; and for the integration of cells into multicellular organisms. Intracellular pathogenic bacteria, such every bit Mycobacteria or Salmonellae, have developed means to control fusion reactions in their host cells. They persist in phagosomes whose fusion with lysosomes they actively suppress-a means to ensure survival inside host cells. The past decade has witnessed rapid progress in the elucidation of parts of the molecular machinery involved in these membrane fusion reactions. Whereas some elements of the fusion apparatus are remarkably similar in several compartments, in that location is an equally striking divergence of others. The purpose of this review is to highlight common features of different fusion reactions and the concepts that emerged from them but also to stress the differences and challenge parts of the current hypotheses. This review covers only the endoplasmic fusion reactions mentioned above, i.e., reactions initiated by contacts of membranes with their cytoplasmic faces. Ectoplasmic fusion events, which depend on an initial contact of the fusion partners via the membrane surfaces exposed to the surrounding medium are not discussed, nor are topics such equally the entry of enveloped viruses, formation of syncytia, gamete fusion, or vesicle scission (a fusion reaction that leads to the fission of, e.g., transport vesicles).