Martin Badley and Umesh Yogarajah 

Heme A

Heme A is a heme protein that is a coordination complex consisting of a porphyrin

chelating an iron atom.

It was first isolated from a bovine heart muscle in 1962 by Warburg and Gewitz and

shown to be active component of the metalloprotein cyctochrome c oxidase

This protein is naturally produced in many organism and appears as a dichroic green/red

and it is structurally relative of heme B, which is in hemoglobin

Reactions Heme A participate in:

o Reduction of O2 to H2O

o Transfer of electrons from cyctochrome C to O2

o Coupling of O2 reduction to ADP phosphorylation

o Respiratory control processes

It is biosynthetically derived from two enzymes; Heme B to Heme O (Heme O Synthase),

followed by the conversion of Heme O to Heme A (Heme A synthase) which occurs in

the mitochondria of the cell

Figure 1. Chemical structure of Heme A

PAGE 1

     

Jun‐Hyeong Park & Michael Czuczola 

Heme C”ysteine” 

 

The structure of Heme C is composed of a porphyrin ring with peripheral decorations 

Heme C is produced when the thiol groups from 2 Cysteines form covalent thioether bonds with the vinyl groups of Heme B 

o Heme B is attached to a CysXXCysHis pentapeptide segment, where His serves as an axial ligand to the Fe, to form Heme C in Cytochrome C 

Heme C is vital to the electron transport chain as it functions as an electron carrier in Cytochrome C (proteins that contain Heme C are refer to as cytochromes c) 

Cytochrome C can initiate cell apoptosis by releasing from the mitochondria, which will trigger a series of biochemical reactions to activate cell death 

Heme C has a large range of reduction potentials in nature that spans over 1V. Cytochrome C cycles between the reduced ferrous and oxidized ferric states to transfer a single electron  

o Useful in determining the thermodynamics of electron transfer reactions o Useful in observing electron transfer kinetics 

Heme C has to be used instead of Heme B in Cytochrome C because Heme C binds more tightly with covalent bonds while Heme B will dissociate out of the protein because it does not have a high enough binding affinity to the amino acid segment of the motif 

Heme C is the only heme that strictly only participates in electrochemistry. Both of the axial positions of the iron centre are blocked off by His and Cys

2 x

 

Heme B             Heme C 

Cysteine 

PAGE 2

     

4-BACTERIOCHLOROPHYLL-A

By: Claire Tully and Keenan Fast

Bacteriochlorophyll-a is found in purple bacteria, a anoxygenic phototroph, and absorbs

wave lengths of 805nm, and 830-890nm. Bacteriochlorophyll-a is composed a porphyrin ring

that the has two reduced pyrrole groups which is called a bacteriochlorin ring. This type of

chlorophyll is found in the simplest life forms, that evolved about 3.5 billion years ago. During

their evolution, the light assessable was lacking in blue and red light due to dust and other debris

in the atmosphere. These bacteria could harness low energy light to sustain NADP production

and survive. As the debris cleared, the blue light could access organisms which resulted in the

evolution of chlorophyll, and thus able to absorb higher energy wave lengths.

Within the purple sulfur bacteria, photosynthesis occurs using sulfur as a source of

electrons. Sulfur was used for bacteria rather than oxygen because the bacteria are absorbing

lower energy wavelengths in comparison to plants. The lower light energy wave lengths

provided enough energy to remove the electron from sulfur however was not enough energy to

remove an electron from oxygen.

The lamellae in the bacteria have several membrane proteins in which house light

activation centers. The light harvesting complex II is composed of alpha and beta proteins that

form a ring like structure surrounding light harvesting complex I(LHI). LH1 is composed of

bacteriochlorophyll-a as well as carotenoids that are collectively the reaction center. From this

complex photosynthesis can occur.

PAGE 3

     

Heme o[Mg] Brianne Potts and Maissa Belcina

Heme o was first discovered in cytochrome bo3-type QOX in 1991. Cytochrome bo3-type QOX is a terminal oxidase in the aerobic respiratory chain of E. coli. Heme o is contained in Subunit I and forms a binuclear center with CuB where dioxygen is reduced to water. It is also used for aerobic respiration in archaebacteria, bacteria and eukaryotes.

Heme o is synthesized from heme b through selective farnesylation in the presence of farnesyl diphosphate (FPP), divalent cations (Mg2+ or Ca2+), and reducing agents like dithionite.

It also acts as the precursor for heme A. The two heme groups differ at ring position 8 where heme o has a methyl substituent, whereas heme A contains a formyl group.

Tatsushi, M. The Porphyrin Handbook; Kadish, K.M.; Smith, K.M.; Guilard, R.; Academic Press: San Diego, 2003; Vol. 12; p 158.

PAGE 4

     

5-Heme m

By: Chris Aspros

Heme m also known as methemoglobin and is a heme found in the blood that is very close to heme B. The only difference is that the iron is in the ferric state rather than the ferrous state. Since the iron is in a higher oxidation state methemoglobin does not bind to oxygen and increases the affinity of oxygen for other oxygen binding hemoglobin. It is normal to have about 1-2% of heme in the blood as methemoglobin.

Heme m is reduced into heme B via two pathways. The first is the more dominant path and it involves NADH and cytochrome b5 and cytochrome b5 reductase. The second uses NADPH and methemoglobin reductase and this can become the main pathway if methylene blue is added as a cofactor. Once reduced the heme group can accept oxygen again.

One condition characterized by having too much methemoglobin in ones system is called methemoglobinemia and can be both genetic and acquired. Some conditions include cyanosis of the skin and as the amount of methemoglobin concentration in the blood increases conditions can worsen to include dizziness headaches and death. The main treatment for acquired methemoglobinemia is to take in methylene blue

PAGE 5

     

Heme‐B (not in Mb or Hb) 

 

By Drishti Kataria and Matthew Baistrocchi 

 

- The most abundant Heme 

 How does it work in…  

COX‐2 

 

COX‐2 (cyclooxygenase) has 2 functions:  

1. the oxidation of arachidonic acid to ProstaglandinG2 (PGG2)   

2. reduction of PGG2 to form ProstaglandinH2 (PGH2) 

 

‐ 2 active sites: heme group and cyclooxygenase site 

‐ Heme, a prosthetic group, is involved in both the peroxidase and cyclooxygenase 

reactions.  

‐ In the cyclooxygenase active site: heme binds to His‐388 and interacts with Tyr‐

385 forming a tyrosine radical which is necessary for the formation of PGG2 from 

arachidonic acid 

‐ In the peroxidase active site: heme acts as the reducing agent in the reduction of 

PGG2 to form PGH2  

 

Peroxidase 

 

a large group of oxidoreductases that catalyze the oxidation of substrate molecules using hydrogen peroxide as electron acceptor  

‐ Contain heme as cofactor 

‐ A 2 electron reduction where H2O2 is reduced to H2O and the enzyme is 

oxidized 

 

 

PAGE 6

     

Cobalamin aka Vitamin B12          Devon Chapple and Kyle Jackman ‐ 1 of 8 B vitamins; 4 major chemical forms of vitamin B12: Cyanocobalamin, 

hydroxocobalamin and the two coenzyme forms of vitamin B12 (methylcobalamin and adenosylcobalamin) 

‐ Cyanocobalamin o Treat pernicious anemia and can be converted to any active vitamin B12 

compound ‐ Hydroxocobalamin 

o Treat pernicious anemia, cyanide poisoning, optic atrophy, and toxic amblyopia ‐ Methylcobalamin 

o Treatment of peripheral neuropathy, diabetic neuropathy, and preliminary treatment of amyotrophic lateral sclerosis 

‐ Adenosylcobalamin o Cofactor to the methylmalonyl‐CoA mutase enzyme 

‐ Overall functions of vitamin B12 compounds: red blood cell formation, functioning of the brain and the nervous system, as well as the synthesis and regulation of DNA. Used in the metabolism of every cell in the body, and helps to facilitate the release of energy.  

‐ Cobalt metal center in either the +1 or +2 oxidation state.  ‐ Only eukaryotic cells are able to naturally synthesize cobalamin and as a result all of the 

cobalamin in our bodies must be ingested.  ‐ Vitamin B12 deficiency can lead to: pernicious anemia, irritability, low red blood cell 

count, and decreased fertility 

‐  

NN

NNCo+

CONH2

CONH2

CONH2

H2NOC

H2NOC

H2NOC

HN

O

O PO O-

O

OHO

N

OH

N

R

PAGE 7

     

  Presentation #10 – Pb and Heme by Mandy Le and Aaron 

  Lead is a dull gray looking metal when exposed to air and has no confirmed biological function 

even though it is present in the in the human body, enough to be considered a bulk element, 0.12g in a 

70 kg human.  The concentration of lead in the human body is due to it being stored in bones and teeth 

over time and in these small concentrations is relatively harmless.  If lead is in the blood however, it is 

highly toxic and results in lead poisoning, which is defined as being exposed to high concentrations of 

lead resulting in severe health effects.  The Centers for Disease Control (US) has set the upper limit of 

blood lead levels for adults at 10 µg/100 g and for children at 5 µg/100g. Exceeding this amount will 

result in lead poisoning. 

Lead is so toxic that it affects every organ in the human body.  Part of lead's toxicity results from 

its ability to mimic other metals that take part in biological processes, which act as cofactors in many 

enzymatic reactions, this results in the enzyme not being able to function properly and results in 

physiological effects. Among the essential metals that lead is able to mimic are calcium, iron, and zinc. 

Iron is one of the more important metals that lead interferes with, which is essential in our blood.  

Lead disrupts of the activity of an essential enzyme called delta‐aminolevulinic acid dehydratase, or ALAD, 

which is important in the biosynthesis of Heme B, the cofactor found in hemoglobin.  Lead also inhibits the 

enzyme ferrochelatase, another enzyme involved in the formation of heme, which catalyzes the joining 

of protoporphyrin and Fe2+ to form heme.  Lead's interference with heme synthesis results in production 

of zinc protoporphyrin and the development of anemia. Another effect of lead's interference with heme 

synthesis is the buildup of heme precursors, such as aminolevulinic acid, which may be directly or indirectly 

harmful to neurons. 

 

 

 

 

 

 

 

 

Figure 1, the reaction catalysed by Ferrochelatase, which lead inhibits 

  Exposure to high concentrations of lead can result from having an occupation involving radiation 

shields, dental X‐rays, ammunition and various surgical tools.  People working jobs such as welders, auto 

mechanics, battery producers, painters and especially the lead miners will be exposed to high lead 

concentrations.  The everyday person can suffer exposure to lead through paint, soil, water and bullets if 

they fancy the firing range.  Symptoms of lead poisoning may include abdominal pain, constipation, 

headaches, irritability, memory problems, inability to have children, and tingling in the hands and feet. 

In severe cases anemia, seizures, coma, or death can be a result of lead poisoning. 

PAGE 8

     

HemeOxidases Foundinthevastmajorityofeukaryotesandsomeprokaryotes ThemostwellknownandimportanthemeoxidaseisCytochromeCOxidase,itisthe

lastcomplexintheelectrontransportchaininthemitochondrionandisinvolvedininvolvedinaerobicrespiration

Itfacilitatesthereductionofoxygenbydonatingelectronsandregulatingthepumpingofhydrogenions

CytochromeCoxidaseisdividedintosubunitsI&IIo SubunitIIisimportantforacceptingelectronsfromCytochromeco SubunitIisimportantforbindingandreducingoxygeno Bothareimportantforregulatingpumpinghydrogenions

Therearefourmajormetal‐containingmoleculesimportantforreduction:CuA,hemea,hemea3andCuB

Toreducedioxygenintowater,4electronsand4hydrogenionsareneededo Thedioxygenmoleculebindstocytochromecoxidasecomplexo Itreceives2electronsfromhemea3,1electronforCuBand1electronfrom

tyrosine Simultaneously,thereducedoxygenmoleculesreactwithtwoprotonseach,

producingtwowatermolecules Thecytochromecoxidasecomplexisnowoxidized Toreturntogroundstate,thesystemrequires4electrons,whichitreceivesfrom

Cytochromec CytochromeCoxidaseoxidizes4moleculesofCytochromec

o CuAisresponsibleforacceptingelectronsfromCytochromeco Inthegroundstateofthecytochromecoxidasecomplex,anelectron

oscillatesbetweenCuAandhemeao Thatelectronisthendonatedtohemea3,CuBortyrosinewhenanother

oxygenmoleculeisreduced CytochromeCdeficienciescancausemanydifferentcomplications

PAGE 9

     

TOPIC 6: Horseradish Peroxidase Maryam Mohammad & Courtney Dickson 

Peroxidases:  Enzymes  that  catalyze  the  oxidations  of  a  wide  range  of  substrates  using 

hydrogen peroxide. There are two groups (1) Animal peroxidase (2) Plant Peroxidase. There are 

three different classes of plant peroxidases 

  Class I:   intracellular enzymes 

  Class II:  Secreted fungal enzymes 

  Class III:  Secreted plant enzymes – Horseradish peroxidase is class III 

Class III Plant Peroxidases: Are characterized as monomeric glycoproteins (meaning 

carbohydrates attached to peptide chain). Contain four disulfide bonds. Have two calcium sites 

that play an important structural role (taking away calcium has serious effects on the enzyme) 

Horseradish Peroxidase: It is a metalloenzyme containing a heme cofactor. It is found in 

the roots of horseradish plants. There are many different isoenzymes but type C is the one most 

commonly studied and understood.  

Structure: 308 amino acids. 13 alpha helices. 3 beta sheets. Stabilized with disulfide bonds. 

Two  calcium  binding  domains  (1)  distal  –  weaker  (2)  proximal.  Active  site  is  iron  (III) 

protoporphyrin IX 

Iron protopophyrin IX:  The  porphyrin  ring  has  Four 

coordinate bonds within the heme and one coordinate bonds with the 

nitrogen  in  the  imidazole  ring.  The  imidazole  is  attached  to  the 

entire  enzyme  through  His  170.  During  catalysis  hydrogen 

peroxide  binds  to  the  iron  atom  through  the  exposed  heme 

edge to form a six coordinate complex 

Catalytic cycle: oxidizes a wide variety of substrates. Typically phenols, indols, aromatic 

amines, and sulfonates. 

Three stages: AH2 is an electron donor and AH• is a radical 

  STAGE 1:   HRP+ H2O2 → Compound I + H2O       electron removed from both heme and iron 

  STAGE 2:  HRP + H2O2 → Compound I + H2O 

  STAGE 3:   Compound II + AH2 → HRP(+3) + AH• 

Applications in plants: removal of hydrogen peroxide from chloroplasts and cytosol, oxidation 

of toxic compounds, biosynthesis of the cell wall, defense responses towards wounds 

+3 

+2  +2 

PAGE 10

     

Only two differences from heme b 

Replace two methyl groups with Glu 

and Asp 

Heme l

• Heme l structure is a 1,5-bis(hydroxymethyl) derivative of heme b • Though very similar to heme b, heme l is not involved in oxygen transport • Heme l is a prosthetic group of the enzyme Lactoperoxidase (LPO)

Peroxidases: an enzyme that catalyzes the oxidation of a particular substrate by hydrogen peroxide Lactoperoxidase is a mammalian peroxidase enzyme secreted from mammary, salivary, and other mucosal glands

• Catalyzes the oxidation of thiocyanate, bromide and iodide in the presence of hydrogen peroxide • These relatively short lived oxidized intermediates have potent bactericidal effects, hence

lactoperoxidase is part of the antimicrobial defense system in tissues Important to note: Lactoperoxidase has no antibacterial effect on its own but has the ability to oxidise the thiocyanate ion (SCN-) or other halides in the presence of hydrogen peroxide (H2O2) (these components also exist naturally in tears, saliva, and gastric juices) Chemistry

reduced acceptor + H2O2 → oxidized acceptor + H2O

thiocyanate (SCN−) → hypothiocyanite (OSCN−) bromide (Br−) → hypobromite (BrO−)

iodide (I−) → hypoiodite (IO−)

PAGE 11