Coenzyme may be tightly bound to the protein = prosthetic group

Ex. = Heme in hemoglobin

 

Or it may be free to diffuse away from the enzyme, acting as an additional substrate = cofactor

Ex. = FAD and NAD (ATP) (Static Images)

see also stick model of NAD

see also ATP using Chime

This could also include cations required for many reactions

Ex. = Mg or Zn

Electron Carriers in Metabolism

In aerobic metabolism, oxidation of electrons from substrates eventually go to oxygen. The electrons are carried by molecules which can themselves be reversably oxidized and reduced:

Reduced = gain of electrons -----> oxidizing agent (leads to loss of electrons in other molecule)

Oxidized = loss of electrons -----> reducing agent (leads to gain of electrons in other molecule)

• Flavins (FAD and FMN)
• These are the major electron carriers in the oxidation of fuels
• MOST of the reducing power in these molecules goes to make ATP through oxidative phosphorylation
• Flavin adenine dinucleotide (FAD)(figure from Biochemistry Illustrated)(Stryer Fig. 17-18 to 17-19)
• FAD = oxidized form
• FADH₂ = reduced form
• Reduction involves the two unsubstituted N atoms of the isoalloxazine structure
• The flavins are associated with dehydrogenase reactions (flavoprotein dehydrogenases)
• Flavin mononucleotide (FMN)
• Riboflavin phosphate without adenosine monophosphate
• Flavin moiety is derived from riboflavin which is vitamin B₂

• Pyridine nucleotides (NAD+/NADP+)(figure from Biochemistry Illustrated)(Stryer Fig. 17-17)
• Nicotinamide adenine dinucleotide (NAD+) and Nicotinamide adenine dinucleotide phosphate (NADP+)
• NAD+ and NADP+ are the oxidized forms
• NADH and NADPH are the reduced forms

RH₂ + NAD⁺ <==>2 electrons + H⁺ <==> R + NADH + H⁺

• These compounds are the major electron donors in reductive biosynthesis reactions
• Reducing power is used to reduce oxidized precursors for biosynthesis

For example:



• The Ratios of these molecules vary between mitochondrion and cytoplasm which reflects where they are generated and where they are used
• NAD:NADH is 5-9:1 in mito and 1200:1 in cytoplasm (contributes to cytoplasmic mass action effect)
• NADP:NAHPH is 1:1 in cytoplasm
• ATP:ADP is 1:50 in mitochondrion and 150:1 in cytoplasm (contributes to cytoplasmic mass action effect

Involved in many acetly transfer reactions ---> Acetyl coenzyme A

Carrier of high energy via thioester (- 7.5 kcal/mol)

Derived from pantothenate in diet

 

 

 
 
 

Carries acetyl groups (such as acetate): linked to S atom in thioester (see Stryer Fig. 17-10)

---

Interchange of activated groups done often by carriers in cell (see Stryer Table 17-2)

Many of these carriers are vitamins which is a common theme

• Lipoamide = acyl carrier
• Thiamine pyrophosphate = aldehyde carrier (Vitamin B₁)
• Biotin = CO₂ carrier (carboxylation/decarboxylation)(covalently bound to Enzyme via carboxyl)
• Tetrahydrofolate = 1-carbon units (methyl groups: UMP ----> TMP)(Folate)
• S-adenosylmethionine = methyl carrier
• Uridine diphosphate glucose = glucose carrier

Cobalamin (Vitamin B₁₂)

• Alleviates symptoms of pernicious anemia
• Transfer of methyl groups

 

Pyridoxal phosphate (Vitamin B₆) -- common in food and from intestinal flora

• Acts as a coenzyme in transamination and decarboxylation reactions

 

Ascorbate or ascorbic acid (Vitamin C)(reducing agent) -- present in fresh fruit and vegetables

• Required for hydroxylation of proline residues in collagen
• Deficiency = scurvy (defective connective tissue = collagen)

Activator ions - activated enzymes (loosely bound K, Mg, Ca)
Metal ions of metalloenzymes (tightly bound Fe, Zn, Cu, Co)