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Control of catabolic pathways

Enzymes, proteins, electron carriers, and pumps that play roles in glycolysis, the citric acid cycle, and the electron transport chain tend to catalyze non-reversible reactions. In other words, if the initial reaction takes place, the pathway is committed to proceeding with the remaining reactions. Whether a particular enzyme activity is released depends upon the energy needs of the cell (as reflected by the levels of ATP, ADP, and AMP).


The control of glycolysis begins with the first enzyme in the pathway, hexokinase ( [link] ). This enzyme catalyzes the phosphorylation of glucose, which helps to prepare the compound for cleavage in a later step. The presence of the negatively charged phosphate in the molecule also prevents the sugar from leaving the cell. When hexokinase is inhibited, glucose diffuses out of the cell and does not become a substrate for the respiration pathways in that tissue. The product of the hexokinase reaction is glucose-6-phosphate, which accumulates when a later enzyme, phosphofructokinase, is inhibited.

This illustration shows that glycolysis is regulated via three key enzymes: hexokinase phosphofructokinase, and phosphoglycerate kinase. The first two enzymes hydrolyze an ATP and the third one produces ATP.
The glycolysis pathway is primarily regulated at the three key enzymatic steps (1, 2, and 7) as indicated. Note that the first two steps that are regulated occur early in the pathway and involve hydrolysis of ATP.

Phosphofructokinase is the main enzyme controlled in glycolysis. High levels of ATP, citrate, or a lower, more acidic pH decrease the enzyme’s activity. An increase in citrate concentration can occur because of a blockage in the citric acid cycle. Fermentation, with its production of organic acids like lactic acid, frequently accounts for the increased acidity in a cell; however, the products of fermentation do not typically accumulate in cells.

The last step in glycolysis is catalyzed by pyruvate kinase. The pyruvate produced can proceed to be catabolized or converted into the amino acid alanine. If no more energy is needed and alanine is in adequate supply, the enzyme is inhibited. The enzyme’s activity is increased when fructose-1,6-bisphosphate levels increase. (Recall that fructose-1,6-bisphosphate is an intermediate in the first half of glycolysis.) The regulation of pyruvate kinase involves phosphorylation by a kinase (pyruvate kinase kinase), resulting in a less-active enzyme. Dephosphorylation by a phosphatase reactivates it. Pyruvate kinase is also regulated by ATP (a negative allosteric effect).

If more energy is needed, more pyruvate will be converted into acetyl CoA through the action of pyruvate dehydrogenase. If either acetyl groups or NADH accumulate, there is less need for the reaction and the rate decreases. Pyruvate dehydrogenase is also regulated by phosphorylation: A kinase phosphorylates it to form an inactive enzyme, and a phosphatase reactivates it. The kinase and the phosphatase are also regulated.

Citric acid cycle

The citric acid cycle is controlled through the enzymes that catalyze the reactions that make the first two molecules of NADH ( [link] ). These enzymes are isocitrate dehydrogenase and α -ketoglutarate dehydrogenase. When adequate ATP and NADH levels are available, the rates of these reactions decrease. When more ATP is needed, as reflected in rising ADP levels, the rate increases. α -Ketoglutarate dehydrogenase will also be affected by the levels of succinyl CoA—a subsequent intermediate in the cycle—causing a decrease in activity. A decrease in the rate of operation of the pathway at this point is not necessarily negative, as the increased levels of the α -ketoglutarate not used by the citric acid cycle can be used by the cell for amino acid (glutamate) synthesis.

Electron transport chain

Specific enzymes of the electron transport chain are unaffected by feedback inhibition, but the rate of electron transport through the pathway is affected by the levels of ADP and ATP. Greater ATP consumption by a cell is indicated by a buildup of ADP. As ATP usage decreases, the concentration of ADP decreases, and now, ATP begins to build up in the cell. This change is the relative concentration of ADP to ATP triggers the cell to slow down the electron transport chain.

Visit this site to see an animation of the electron transport chain and ATP synthesis.

For a summary of feedback controls in cellular respiration, see [link] .

Summary of Feedback Controls in Cellular Respiration
Pathway Enzyme affected Elevated levels of effector Effect on pathway activity
glycolysis hexokinase glucose-6-phosphate decrease
phosphofructokinase low-energy charge (ATP, AMP), fructose-6-phosphate via fructose-2,6-bisphosphate increase
high-energy charge (ATP, AMP), citrate, acidic pH decrease
pyruvate kinase fructose-1,6-bisphosphate increase
high-energy charge (ATP, AMP), alanine decrease
pyruvate to acetyl CoA conversion pyruvate dehydrogenase ADP, pyruvate increase
acetyl CoA, ATP, NADH decrease
citric acid cycle isocitrate dehydrogenase ADP increase
ATP, NADH decrease
α -ketoglutarate dehydrogenase Calcium ions, ADP increase
ATP, NADH, succinyl CoA decrease
electron transport chain ADP increase
ATP decrease

Section summary

Cellular respiration is controlled by a variety of means. The entry of glucose into a cell is controlled by the transport proteins that aid glucose passage through the cell membrane. Most of the control of the respiration processes is accomplished through the control of specific enzymes in the pathways. This is a type of negative feedback, turning the enzymes off. The enzymes respond most often to the levels of the available nucleosides ATP, ADP, AMP, NAD + , and FAD. Other intermediates of the pathway also affect certain enzymes in the systems.

Questions & Answers

What is cytoplasm
Nitta Reply
Parasitic adaptation of tapeworm
Angela Reply
Describe osmoregulator or osmoconformers and how these tools allow animals to adapt to different environment.
Alick Reply
describe the secondary function of a leaf to a plant.
Twizera Reply
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Khushboy Reply
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what is the difference between primary and secondary active transport in detail? I didn't understand the steps in the textbook specifically
Fathima Reply
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what is the meaning of connective tissue?
Mohammed Reply
what are the characteristics of living things
Owolo Reply
what's the meaning of connective tissue?
Reproduction, adaptation, interaction, movement, growth, respiration, made of cells, responsive to environment (homeostasis), metabolic action (consumption of food converted into energy)
Movement, reproduction, nutrition, irritability, growth, excretion, respiration, death, adaptation, competition
state two most important factors that favour exponential growth of population of a gazelle in a pack
Eliza Reply
what are the two types of electron microscope
Sharlom Reply
light microscope and early microscope
Enzymes are biological catalyst which alter any reaction and protein in nature
Nkoue Reply
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What is translation and transcription
Transcription is making RNA from DNA. Translation is going from RNA to proteins.
full meaning of RNA and DNA
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Mohammed khalfan, In biology, homeostasis is the state of steady internal, physical, and chemical conditions maintained by living systems.[1] This dynamic state of equilibrium is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid bal
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Royd Reply
enzymes are biological catalyst that speed up chemical reaction.
What are enzymes?
Enzymes are made of proteins and lower the energy of activation. In other words, they bring things together which helps to lower the amount of energy for a reaction to go forward.
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These are catalyst that speeds up the chemical reaction.
What is connective tissue?
what homeostits means ?
what is a spirogyra
Talabi Reply
Spirogyra is a filamentous chlorophyte green algae of the order Zygnematales. It is named for the helical or spiral arrangement of the chloroplasts. That is characteristic of the genus. It is commonly found in freshwater habitats. And there are more than 400 species of Spirogyra in the world.
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Bello Reply
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A cell is the smallest living unit.
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what is eutrophication
Chinaza Reply
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Eutrophication is an enrichment of water by nutrient salts that causes structural changes to the ecosystem such as: increased production of algae and aquatic plants, depletion of fish species, general deterioration of water quality and other effects that reduce and preclude use.

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