Page 212 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

P1: GTY Final pages
Encyclopedia of Physical Science and Technology EN017G-116 August 2, 2001 18:14

520 Vitamins and Coenzymes

provides the necessary shape and chemical properties to responding carbonyl compounds—aldehydes or ketones.
allow it to bind into crevices within the active sites of a At the same time, many carbonyl compounds are reduced
variety of proteins. There it not only fits snugly but has to alcohols. Sometimes the oxidation and reduction pro-
electrostatic bonding interactions that allow the proteins cesses are linked. A well-known example is the oxidation
to hold it in just the correct orientation for its function. of glyceraldehyde 3-phosphate during the breakdown of
Curiously, the exact biological need for the unusual struc- glucose,aprocessthatoccursinbacteria,yeast,andthehu-
+
+
ture of the vitamin is still obscure. The chemically func- man body. In all cases NAD is reduced to NADH + H .
+
tional end of coenzyme A is the sulfhydryl ( SH) group The latter is reoxidized to NAD in the human body, but
which is added on to the vitamin structure by cells, as in lactic acid bacteria the NADH is used (always together
+
shown in Fig. 10. Before coenzyme A can function it must with an H ion) to reduce pyruvic acid to lactic acid. This
be combined in a thioester linkage with a carboxylic acid provides a balanced fermentation process that requires no
such as acetic acid, or a long-chain fatty acid, as illus- oxygen. Under conditions of extreme exertion, e.g., in a
trated in Fig. 10 (right). It is customary in discussions of 100-meter race, the lactic acid fermentation fuels human
metabolism to indicate the bulk of the coenzyme structure muscles. In yeast, a similar fermentation reduces acetalde-
as CoA. The free coenzyme is designated CoA SH, and hyde to ethanol, indirectly providing energy for the cell.
in a thioester the hydrogen of the SH group is replaced Why are there two similar coenzymes NAD and
by an acyl group. The coenzyme has two functions. First, NADP? A generalization that holds in many instances is
+
it can carry the acyl group from one protein to the next in a that NAD initiates dehydrogenation (oxidation) while
metabolic sequence, such as that of Fig. 12. Second, it can NADPH acts as a biological reductant. This permits ox-
+
activate a hydrogen atom adjacent to the carbonyl (C O) idative pathways utilizing NAD to occur at the same time
+
group for removal of a proton (H ) by a catalytic group of as reductive processes that utilize NADPH. Cells of aer-
basicnature,suchas NH 2 ,presentintheprotein.Thecar- obic organisms often keep the concentration ratio of the
bonyl group in a thioester is an electron accepting group, reactants [NAD ]/[NADH] high at the same time that the
+
whose facilitation of the proton removal is often indicated ratio [NADPH] / [NADP ] is also high. Nicotinamide is
+
by curved arrows, as shown in Fig. 10 (right). The product a very stable compound, but the coenzyme forms are sur-
of this proton removal is a reactive anion which is able prisingly easily destroyed. The reduced forms NADH and
to undergo formation or cleavage of carbon–carbon bonds NADPH are extremely unstable below pH 7, undergoing
+
+
or dehydrogenation by the riboflavin-containing FAD, as ring opening reactions. NAD and NADP are unstable
shown in Fig. 12. at high pH, hydroxide ions adding to double bonds in
Other coenzymes and prosthetic groups may also act the nicotinamide ring with subsequent destruction of the
as acyl group carriers. For the biosynthesis of fatty acids, coenzymes. It is not surprising that our bodies need a daily
a shortened version of coenzyme A (phosphopantetheine, supply of this vitamin.
+
Fig. 10), is covalently linked to appropriate proteins. Dur- LikeNAD ,FADandthesimplerriboflavinmonophos-
ing carbohydrate metabolism, a prosthetic group consist- phate (FMN) often serve as an acceptor of a hydride (H )
−
ing of bound lipoic acid (Fig. 11) carries acetyl groups. ion. However, FAD is a more powerful oxidant than is
+
Both acetyl groups and long-chain fatty acyl groups are NAD . This fact is indicated in a quantitative way by
carried across membranes into and out of mitochondria the standard reduction potential, which biochemists tabu-
while attached to the unusual amino acid carnitine (Fig. 4). late for pH 7. At this pH the standard hydrogen electrode

0
Carnitine is not a vitamin but acts as a coenzyme. potential E (for the couple H /H 2 ) is −0.414 V while
+
that for the powerful oxidant O 2 (O 2 /H 2 O) is +0.815 at

0
25 C. For the NAD /NADH couple E is −0.32 V and
+
◦
+
B. Nicotinamide Adenine Dinucleotide (NAD ) for FAD/FADH 2 it is −0.21 V. However, since FAD and
and Flavin Adenine Dinucleotide (FAD), FADH 2 are often tightly bound as flavoproteins, the value
Hydrogen and Electron Carriers 0
of E for flavoproteins varies over a broad range from
Because of the linkage of the vitamin nicotinamide to the −0.49 to +0.19 V. The value depends upon the relative
+
ring of the sugar ribose, NAD and its relative NADP + strength of binding of the oxidized and reduced forms of
(which carries an extra phospho group in its structure; FAD to the specific catalytic proteins. In the β oxidation
Fig. 8) can be reduced by transfer of a hydrogen atom of fatty acids (Fig. 12), the powerful oxidizing properties
from an alcohol or other suitable substrate to the 4 posi- of FAD make it possible to remove a C3 hydrogen atom
−
tion of the ring. As illustrated in Fig. 8, the transfer is that as H either after or concurrently with the removal of a
−
of a hydrogen atom plus an electron (a hydride ion H ). proton from C2. The latter requires participation of a basic
+
NAD plays this role in many biological dehydrogena- group from the protein as well as activation by the CoA
tion reactions which convert various alcohols into the cor- thioester group (step b in Fig. 12). The thioester group