There are a large number of enzymes in the dehydrogenase class. Their two main functions are as follows:

 1. Transfer of hydrogen from one substrate to another in a coupled oxidation–reduction reaction (Figure 1). These dehydrogenases often utilize common coenzymes or hydro gen carriers, for example, nicotinamide adenine dinucleotide (NAD+). This type of reaction in which one substrate is oxidized/reduced at the expense of another is freely reversible, enabling reducing equivalents to be transferred within the cell and oxidative processes to occur in the absence of oxygen, such as during the anaerobic phase of glycolysis .

Fig1. Oxidation of a metabolite catalyzed by cou pled dehydrogenases.

 2. Transfer of electrons from substrate to oxygen in the respiratory chain electron transport system .

Many Dehydrogenases Depend on Nicotinamide Coenzymes

 These dehydrogenases use NAD+ or nicotinamide adenine dinucleotide phosphate (NADP+)—or both—which are formed in the body from the vitamin niacin (see Chapter 44). The structure of NAD+ is shown in Figure 2. NADP+ has a phosphate group esterified to the 2′ hydroxyl of its adenosine moiety, but otherwise is identical to NAD+. The oxidized forms of both nucleotides have a positive charge on the nitrogen atom of the nicotinamide moiety as indicated in Figure2. The coenzymes are reduced by the specific substrate of the dehydrogenase and reoxidized by a suitable electron acceptor. They are able to freely and reversibly dissociate from their respective apoenzymes.

Fig2. Oxidation and reduction of nicotinamide coenzymes. Nicotinamide coenzymes consist of a nicotinamide ring linked to an adenosine via a ribose and a phosphate group, forming a dinucleotide. NAD+/NADH are shown, but NADP+/NADPH are identical except that they have a phosphate group esterified to the 2' OH of the adenosine. An oxidation reaction involves the transfer of two electrons and one H+ from the substrate to the nicotinamide ring of NAD+ forming NADH and the oxidized product. The remaining hydro- gen of the hydrogen pair removed from the substrate remains free as a hydrogen ion. NADH is oxidized to NAD+ by the reverse reaction. R, the part of the molecule unchanged in the oxidation/reduction reaction.

Generally, NAD-linked dehydrogenases catalyze oxidoreduction reactions of the type:

When a substrate is oxidized, it loses two hydrogen atoms and two electrons. One H+ and both electrons are accepted by NAD+ to form NADH and the other H+ is released (see Figure 2). Many such reactions occur in the oxidative pathways of metabolism, particularly in glycolysis (see Chapter 17) and the citric acid cycle (see Chapter 16). NADH is generated in these pathways via the oxidation of fuel molecules, and NAD+ is regenerated by the oxidation of NADH as it transfers the electrons to O2 via the respiratory chain in mitochondria, a process which leads to the formation of ATP (see Chapter 13).

NADP-linked dehydrogenases are found characteristically in biosynthetic pathways where reductive reactions are required, as in the extramitochondrial pathway of fatty acid synthesis (see Chapter 23) and steroid synthesis (see Chapter 26)—and also in the pentose phosphate pathway (see Chapter 20).

Other Dehydrogenases Depend on Riboflavin

 The flavin groups such as FMN and FAD are associated with dehydrogenases as well as with oxidases as described earlier. FAD is the electron acceptor in reactions of the type:

FAD accepts two electrons and two H+ in the reaction , forming FADH2 . Flavin groups are generally more tightly bound to their apoenzymes than are the nicotinamide coenzymes. Most of the riboflavin-linked dehydrogenases are concerned with electron transport in (or to) the respiratory chain (see Chapter 13).NADH dehydrogenase acts as a carrier of electrons between NADH and the components of higher redox potential . Other dehydrogenases such as succinate dehydrogenase, acyl-CoA dehydrogenase, and mitochondrial glycerol-3-phosphate dehydrogenase transfer reducing equivalents directly from the substrate to the respiratory chain . Another role of the flavin-dependent dehydrogenases is in the dehydrogenation (by dihydrolipoyl dehydrogenase) of reduced lipoate, an intermediate in the oxidative decarboxylation of pyruvate and α-ketoglutarate . The electron transferring flavoprotein (ETF) is an intermediary carrier of electrons between acyl-CoA dehydrogenase and the respiratory chain .

Cytochromes May Also Be Regarded as Dehydrogenases

 The cytochromes are iron-containing hemoproteins in which the iron atom oscillates between Fe³⁺ and Fe²⁺ during oxidation and reduction. Except for cytochrome oxidase (described earlier), they are classified as dehydrogenases. In the respiratory chain, they are involved as carriers of electrons from flavoproteins on the one hand to cytochrome oxidase on the other . Several identifiable cytochromes occur in the respiratory chain, they are; cytochromes b, c1 , c, and cytochrome oxidase (aa3 ). Cytochromes are also found in other locations, for example, the endoplasmic reticulum (cytochromes P450 and b5 ), and in plant cells, bacteria, and yeasts.

مواضيع ذات صلة

اضطرابات استقلاب النوكليوتيدات البيريميدينية

اضطرابات استقلاب النكليوتيدات البورينية

تخليق النوكليوتيدات منقوصة الاكسجين ( dNTPs )

تقويض النوكليوتيدات البيريميدينية

Oxidases Use Oxygen As A Hydrogen Acceptor

تخليق النكليوتيدات البيريميدينية

تقويض النوكليوتيدات البورينية

تنظيم استحداث البورينات

التخليق الحيوي للنوكليوتيدات البورينية

سبيل كيناز جانوس ومُنبِّغات الإشعار ومنشطات الانتساخ Jak/STATS Pathway

آلية عمل الأنسولين (وغيره من الهرمونات التي تحوي فعالية كيناز التيروزين الداخلية)

آلية عمل هرمونات المجموعة II-C (المرسال الثاني هو الكالسيوم ومشتقات فسفاتيديل الإينوزيتول)