Biochemistry 8.5; Coenzymes, Vitamins, and Essential Metals

What are coenzymes or cofactors?

Ions or small molecules that are bound to enzymes but are not irreversibly changed during catalysis

What vitamins and metals are used in redox reactions? (7)

1) Riboflavin (B2)

2) Niacin (B3)

3) Lipoic Acid

4) Fe

5) Cu

6) Mo

7) V

What is the coenzyme and coenzyme reaction of Thiamine (B1)

Thiamine pyrophosphate; Activation and transfer of aldehydes

What is the coenzyme and coenzyme reaction of pantothenic acid (B5)

Coenzyme A; Acyl group transfer and activation

What is the coenzyme and coenzyme reaction of pyridoxine

Pyridoxal phosphate; Various amino acid activation reactions

What is the coenzyme and coenzyme reaction of biotin (B7)

Biotin; CO2 activation and transfer

What is the coenzyme and coenzyme reaction of lipoic acid

Lipoamide; Redox and acyl group activation

What is the coenzyme and coenzyme reaction of folic acid (B9)

Tetrahydrofolate; Activation and transfer of single-carbon functional groups

What is the coenzyme and coenzyme reaction of B12

Adenosyl and methyl cobalamin; Isomerizations and methyl group transfers

What is the related enzyme and role of Zn

Alcohol dehydrogenase; Helps bind NAD+

What is the related enzyme and role of Mn

Histidine ammonia lyase; Aids in catalysis by electron withdrawal

What is the related enzyme and role of Co

Glutamate mutase; part of cobalamin coenzyme

What is the related enzyme and role of Ni

Urease; catalytic site

What is the related enzyme and role of Se

Glutathione peroxidase; replaces S in one cysteine active site

What is the related enzyme and role of Mg

Many kinases; Helps bind ATP

What does the complexity of globular protein structure and variety of side-chain structures allow?

The formation of many kinds of catalytic sites

What does the variability of catalytic sites allow?

Allows enzymes to act as catalysts for many reactions.

What is important to note about coenzyme structure?

Complex organic structures that cannot be synthesized by some organisms (especially mammals).

What is another name for the water-soluble vitamins?

vitamin-B complexes

Why are the water soluble/vitamin-B complexes so important in metabolism?

They are precursors of several coenzymes.

What is an important concept regarding vitamin precursors?

Many essential vitamins are constituents of coenzymes

What is a major example of the nicotinamide nucleotides?

Nicotinamide adenine dinucelotide (NAD+)

What is NAD+ derived from?

Niacin

What are the oxidized forms of NAD?

O) NAD+

R) NADH

What is closely related cofactor of NAD?

Nicotinamide adenine dinucleotide phosphate (NADP+)

How does NADP differ from NAD?

NADP has a phosphoryl group at the 2’ position of the ribose attached to the adenine base.

/What vitamin is this

Niacin (B3)

What are vitamin deficiencies often associated with?

Nutritional disease

How was the concept of a vitamin first described?

Observation that beriberi could be treated by thiamine

Where is thiamine present naturally?

Unpolished but not refined rice

What does a niacin deficiency cause?

Pellagra

Where is pellagra common?

Populations with high malnutrition or chronic alcoholism

What part of NAD+ is responsible for its metabolic functions, and why?

The nicotinamide portion because it can be reduced and serve as an oxidizing agent.

What does the oxidizing agent part of NAD do to a nicotinamide ring?

Adds 2 electrons and a proton.

Is the formation of NADH reversible?

Yes, and it is a reducing agent in some reactions.

What is the formal term for the reverse NADH reaction?

Hydride ion transfer

What is a typical reaction where NAD+ acts as an oxidizing agent?

The conversion of alcohols to aldehydes or ketones.

Which hydrogen is transferred to NAD+ in the NADH reaction?

The C-linked H, NOT the O-linked H

Is the hydride ion transfer stereospecific?

Yes.

How can a H be favored when the substrate molecule has a plane of symmetry?

It depends on the asymmetric nature of the enzyme surface that the NAD+ and the alcohol are bound.

What must happen for two atoms to be called prochiral?

The molecule itself must be bound by at least 3 points to an asymmetric object.

Why is the transfer of a hydrogen in a prochiral reaction always to a specific face of the ring?

The two faces are NOT equivalent in the asymmetric active site of an enzyme.

In what cases is a NAD+ acting more like a second substrate than a true cofactor?

After oxidizing the substrate, the reduced form (NADH) leaves the enzyme and reoxidized and ready to bind to another enzyme.

How is NAD+ different from most substrates?

They are continually recycled in the cell and- like a catalyst- continually ready to be reused by the cell.

“Metalloenzymes”

Metal ions that act like a coenzyme and giving the enzyme a property it would not possess in its absence.

What is an important concept regarding metal ions?

Some enzymes require metal ions for their catalytic function.

What is a reaction of a zinc metalloenzyme?

The reaction of carboxypeptidase A binding the water molecule that attacks the carbonyl of the scissile bond and acts as an electrostatic catalyst.

What does the zinc ion do in the carboxypeptidase reaction?

Stabilizes the tetrahedral oxyanion in the transition state and the intermediate state.

What is another use of the metal in a metalloenzyme?

Sometimes serve as a redox reagent.

Why is the iron in catalase an electron exchanger?

It involves reduction and oxidatoin of H2O2 and is reversibly oxidized and reduced.

Why is Mg2+ necessary in most ATP reactions?

The Mg-ATP complex is a better substrate than ATP itself.