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Isocitrate Dehydrogenase Reaction What type of chemical reaction is involved in the conversion of isocitrate to \(a\) - ketoglutarate? Name and describe the role of any cofactors. What other reaction(s) of the citric acid cycle are of this same type?

Short Answer

Expert verified
The reaction is oxidative decarboxylation involving NAD+ and Mg2+/Mn2+. Similar reactions include α-ketoglutarate to succinyl-CoA conversion.

Step by step solution

01

Identify the type of reaction

The conversion of isocitrate to α-ketoglutarate in the citric acid cycle is an oxidative decarboxylation reaction. This type of reaction involves the removal of a carboxyl group and hydrogen atoms, which are transferred to a cofactor.
02

Determine the cofactors involved

The cofactors involved in this reaction are NAD+ and Mg2+ or Mn2+. NAD+ acts as an electron acceptor, getting reduced to NADH, while Mg2+ or Mn2+ ions help stabilize the transition state and the enzyme's active site.
03

Explore similar reactions in the cycle

Another reaction in the citric acid cycle that is also an oxidative decarboxylation is the conversion of α-ketoglutarate to succinyl-CoA. This reaction involves the enzyme complex α-ketoglutarate dehydrogenase and is also sensitive to cofactors like NAD+ and coenzyme A.

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Key Concepts

These are the key concepts you need to understand to accurately answer the question.

Oxidative Decarboxylation
Oxidative decarboxylation is a critical biochemical reaction commonly found in the citric acid cycle and other metabolic pathways. This reaction type involves two main processes – oxidation and decarboxylation. During oxidative decarboxylation, a molecule loses a carbon atom, often in the form of carbon dioxide. Simultaneously, electrons are removed from the molecule.
This loss of electrons constitutes the oxidation part of the reaction.
In the citric acid cycle, oxidative decarboxylation is illustrated by the conversion of isocitrate to α-ketoglutarate. Here, a carboxyl group is removed as CO2, while electrons are transferred to a cofactor.
  • Decarboxylation: Removal of CO2.
  • Oxidation: Transfer of electrons.
Another example in the cycle is when α-ketoglutarate is transformed into succinyl-CoA, showcasing the importance of these reactions in energy production and carbon management within cells.
Isocitrate Dehydrogenase
Isocitrate dehydrogenase is an enzyme pivotal to the citric acid cycle, catalyzing the conversion of isocitrate to α-ketoglutarate. This reaction is an example of oxidative decarboxylation, highlighting the enzyme's role in facilitating complex biochemical transformations.
Isocitrate dehydrogenase operates by binding to substrates like isocitrate, along with necessary cofactors like NAD+ or NADP+.
These cofactors accept the hydrogen atoms removed during the reaction, getting reduced in the process.
  • NAD+ or NADP+ as cofactors.
  • Catalysis of oxidative decarboxylation.
Furthermore, isocitrate dehydrogenase is a regulatory point in the cycle, meaning its activity can influence the cycle's rate. It is sensitive to the cell's energy needs, being activated or inhibited by certain metabolites, adjusting its function accordingly.
Cofactors in Biochemistry
Cofactors are non-protein chemical compounds that aid enzymes in performing catalytic reactions efficiently. In biochemistry, they play numerous roles, mainly acting as carriers for chemical groups, electrons, or atoms during the reaction processes.
In the context of the citric acid cycle, NAD+, Mg2+, and Mn2+ are crucial cofactors.
  • NAD+: Acts as an electron carrier, accepting electrons to form NADH.
  • Mg2+ and Mn2+: Stabilize reaction intermediates and support enzyme activity.
Without these cofactors, many enzymatic processes would either not occur or proceed very slowly. They are central to the citric acid cycle, ensuring that energy production and metabolic regulation proceed smoothly. Understanding the role and mechanism of each cofactor provides insight into their importance not only in the citric acid cycle but also throughout cellular metabolism.

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Most popular questions from this chapter

Labeling Studies in Isolated Mitochondria Biochemists have often delineated the metabolic pathways of organic compounds by using a radioactively labeled substrate and following the fate of the label. a. How can you determine whether a suspension of isolated mitochondria metabolizes added glucose to \(\mathrm{CO}_{2}\) and \(\mathrm{H}_{2} \mathrm{O}\) ? b. Suppose you add a brief pulse of \(\left[3-{ }^{14} \mathrm{C}\right]\) pyruvate (labeled in the methyl position) to the mitochondria. After one turn of the citric acid cycle, what is the location of the \({ }^{14} \mathrm{C}\) in the oxaloacetate? Explain by tracing the \({ }^{14} \mathrm{C}\) label through the pathway. How many turns of the cycle are required to release all the \(\left[3-{ }^{14} \mathrm{C}\right]\) pyruvate as \(\mathrm{CO}_{2}\) ?

Regulation of the Pyruvate Dehydrogenase Complex In animal tissues, the ratio of active, unphosphorylated to inactive, phosphorylated PDH complex regulates the rate of conversion of pyruvate to acetyl-CoA. Determine what happens to the rate of this reaction when a preparation of rabbit muscle mitochondria containing the PDH complex is treated with (a) pyruvate dehydrogenase kinase, ATP, and \(\mathrm{NADH}\); (b) pyruvate dehydrogenase phosphatase and \(\mathrm{Ca}^{2+}\); (c) malonate.

How the Citric Acid Cycle Was Discovered The detailed biochemistry of the citric acid cycle was determined by several researchers over a period of decades. In a 1937 article, Krebs and Johnson summarized their work and the work of others in the first published description of this pathway. The methods used by these researchers were very different from those of modern biochemistry. Radioactive tracers were not commonly available until the 1940 s, so Krebs and other researchers had to use nontracer techniques to work out the pathway. Using freshly prepared samples of pigeon breast muscle, they determined oxygen consumption by suspending minced muscle in buffer in a sealed flask and measuring the volume (in \(\mu \mathrm{L}\) ) of oxygen consumed under different conditions. They measured levels of substrates (intermediates) by treating samples with acid to remove contaminating proteins, then assaying the quantities of various small organic molecules. The two key observations that led Krebs and colleagues to propose a citric acid cycle as opposed to a linear pathway (like that of glycolysis) were made in the following experiments. Experiment I: They incubated \(460 \mathrm{mg}\) of minced muscle in 3 \(\mathrm{mL}\) of buffer at \(40^{\circ} \mathrm{C}\) for 150 minutes. Addition of citrate increased \(\mathrm{O}_{2}\) consumption by \(893 \mu \mathrm{L}\) compared with samples without added citrate. They calculated, based on the \(\mathrm{O}_{2}\) consumed during respiration of other carbon-containing compounds, that the expected \(\mathrm{O}_{2}\) consumption for complete respiration of this quantity of citrate was only \(302 \mu \mathrm{L}\). Experiment II: They measured \(\mathrm{O}_{2}\) consumption by \(460 \mathrm{mg}\) of minced muscle in \(3 \mathrm{~mL}\) of buffer when incubated with citrate and/or with 1-phosphoglycerol (glycerol 1-phosphate; this was known to be readily oxidized by cellular respiration) at \(40^{\circ} \mathrm{C}\) for 140 minutes. The results are shown in the table. \begin{tabular}{llc} 1 & No extra & 342 \\ \hline 2 & \(0.3 \mathrm{~mL} 0.2 \mathrm{M}\) 1-phosphoglycerol & 757 \\ \hline 3 & \(0.15 \mathrm{~mL} 0.02 \mathrm{M}\) citrate & 431 \\ \hline 4 & \(0.3 \mathrm{~mL} 0.2 \mathrm{M}\) 1-phosphoglycerol and \(0.15 \mathrm{~mL} 0.02\) & 1,385 \\ & M citrate & \\ \hline \end{tabular} a. Why is \(\mathrm{O}_{2}\) consumption a good measure of cellular respiration? b. Why does sample 1 (unsupplemented muscle tissue) consume some oxygen? c. Based on the results for samples 2 and 3 , can you conclude that 1-phosphoglycerol and citrate serve as substrates for cellular respiration in this system? Explain your reasoning. d. Krebs and colleagues used the results from these experiments to argue that citrate was "catalytic"that it helped the muscle tissue samples metabolize 1 phosphoglycerol more completely. How would you use their data to make this argument? e. Krebs and colleagues further argued that citrate was not simply consumed by these reactions, but had to be regenerated. Therefore, the reactions had to be a cycle rather than a linear pathway. How would you make this argument? Other researchers had found that arsenate \(\left(\mathrm{AsO}_{4}^{3-}\right)\) inhibits \(a\)-ketoglutarate dehydrogenase and that malonate inhibits succinate dehydrogenase. f. Krebs and coworkers found that muscle tissue samples treated with arsenate and citrate would consume citrate only in the presence of oxygen; under these conditions, oxygen was consumed. Based on the pathway in Figure 16-7, what was the citrate converted to in this experiment, and why did the samples consume oxygen? In their article, Krebs and Johnson further reported the following: (1) In the presence of arsenate, \(5.48\) mmol of citrate was converted to \(5.07 \mathrm{mmol}\) of \(a\) ketoglutarate. (2) In the presence of malonate, citrate was quantitatively converted to large amounts of succinate and small amounts of \(a\)-ketoglutarate. (3) Addition of oxaloacetate in the absence of oxygen led to production of a large amount of citrate; the amount was increased if glucose was also added. Other workers had found the following pathway in similar muscle tissue preparations: Succinate \(\rightarrow\) fumarate \(\rightarrow\) malate \(\rightarrow\) oxaloacetate \(\longrightarrow \mathrm{p}\) g. Based only on the data presented in this problem, what is the order of the intermediates in the citric acid cycle? How does this compare with Figure 16-7? Explain your reasoning.

Thiamine Deficiency Individuals with a thiamine-deficient diet have relatively high levels of pyruvate in their blood. Explain this in biochemical terms.

Regulation of Pyruvate Carboxylase The carboxylation of pyruvate by pyruvate carboxylase occurs at a very low rate unless acetyl-CoA, a positive allosteric modulator, is present. If you have just eaten a meal rich in fatty acids (triacylglycerols) but low in carbohydrates (glucose), how does this regulatory property shut down the oxidation of glucose to \(\mathrm{CO}_{2}\) and \(\mathrm{H}_{2} \mathrm{O}\) but increase the oxidation of acetylCoA derived from fatty acids?

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