Skip to main content

Glycolysis summary, steps of glycolysis, regulation of glycolysis

Definition:

Glycolysis is defined as the sequence of reactions metabolizing one molecule of glucose to two molecules of pyruvate or lactate with the simultaneous generation of adenosine triphosphate (ATP). Glycolysis occurs in the cytoplasm. Glycolysis is also known as Embden-Meyerhof-Parnas (EMP) pathway. Glycolysis can occur aerobically as well as anaerobically.

Aerobic glycolysis occurs in the presence of oxygen and produces two molecules of pyruvate. Anaerobic glycolysis occurs in the absence of oxygen or when limited amounts of oxygen are available and it produces two molecules of lactate.

Features:

  • It occurs mainly in the muscle and liver.
  • It is a major pathway for ATP synthesis in tissues that lack mitochondria. Example - cornea, lens, red blood cells.
  • The sub-cellular site is the cytoplasm.
  • It is very essential for the brain which is dependent only on glucose for energy.
  • The reaction of glycolysis can be divided into two main phases - The preparatory phase (step 1 to step 5) and the Payoff phase (step 6 to step 10).

Fig. Glycolysis

Steps of glycolysis:

Preparatory phase:

STEP 1:- The first step of this pathway is the transfer of a phosphoryl group from ATP to glucose to form glucose-6-phosphate (G6P), this reaction is catalyzed by hexokinase in the muscle or glucokinase in the liver. The co-enzyme is ATP for both the enzymes. The co-factor of these two enzymes is magnesium. This step is essentially irreversible.

STEP 2:- In the second step phosphoglucose isomerase (PGI) helps to convert glucose-6-phosphate (G6P) to fructose-6-phosphate (F6P) via isomerization. This is a reversible step.

STEP 3:- In the third step, phosphofructokinase (PFK) phosphorylates F6P to yield fructose 1,6-bisphosphate (F 1,6-BP) with the help of ATP. The co-enzyme of PFK is ATP and the co-factor is magnesium. This is also an irreversible step.

STEP 4:- Step four is catalyzed by the enzyme aldolase. Aldolase helps to cleave F 1,6-BP to form two triose sugars, that are glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). Aldolase helps to split six-carbon F 1,6-BP to GAP and DHAP.

STEP 5:- Only one of the products of the aldol cleavage reaction that is GAP continues along the glycolysis pathway. So, triosephosphate isomerase (TPI) helps to isomerize DHAP to GAPand after this reaction two molecules of GAP are produced.

Payoff phase:

STEP 6:- Reaction six of this pathway involves the oxidation and phosphorylation of GAP by nicotinamide adenine dinucleotide (NAD+) and inorganic phosphate as catalyzed by glyceraldehyde 3-phosphate dehydrogenase (GAPDH) to produce 1,3-bisphosphoglycerate (1,3-BPG) and NADH + H+. This is the crucial reaction of this pathway since a high-energy compound (1,3-BPG) is formed and the reducing equivalents are incorporated into NAD+ to form NADH + H+. The co-enzyme of this enzyme is niacin (NAD+).

STEP 7:- In the seventh step phosphoglycerate kinase (PGK) helps to transfer the high energy compound 1,3-BPG to 3-phosphoglycerate (3-PG) by producing ATP from ADP. This step is the first substrate-level phosphorylation step of this pathway.

STEP 8:- In step eight 3-PG is isomerized to 2-phosphoglycerate (2-PG) by phosphoglycerate mutase (PGM). PGM catalyzes the transfer of a functional group from one position to another on a molecule.

STEP 9:- In step nine 2-PG is dehydrated to phosphoenolpyruvate (PEP) catalyzed by enolase. PEP is a high-energy compound. The co-factor of the enzyme enolase is magnesium.

STEP 10:- In the last step of glycolysis pyruvate kinase (PK) couples the free energy of PEP hydrolysis to synthesize pyruvate and ATP. The enzyme PK requires ADP, magnesium, and potassium for its work. This is the second substrate-level phosphorylation of this pathway. This step is essentially an irreversible step.

Substrate level phosphorylation:

It is a process in which a phosphate group is transferred from a phosphorylated metabolic intermediate directly to ADP or GDP, to form ATP or GTP. So, ATP or GTP is synthesized directly from a high-energy substrate without undergoing an electron transport chain (ETC).

Inhibitors:

  • Enzyme enolase is inhibited by fluoride.
  • Enzyme GAPDH is inhibited by arsenate and iodoacetate.

Generation of acetyl CoA from pyruvate:

The pyruvate that is produced in glycolysis is converted to acetyl CoA by oxidative decarboxylation. This is an irreversible reaction and is catalyzed by a multiple enzyme complex which is known as pyruvate dehydrogenase complex (PDH). PDH is found in the mitochondria and for its efficient work, it requires five co-factors these are lipoamide, thiamine pyrophosphate (TPP), coenzyme A, FAD, and NAD+.

 

Regulation of Glycolysis:

Fig. Overall regulation of glycolysis

Regulation of flux through glycolysis is dependent on tissue, nutritional and hormonal state. The enzymes of glycolysis that are highly controlled are - Hexokinase, PFK-I, and Pyruvate kinase. These enzymes are regulated by covalent modification or allosteric effector or both.
  1. Hexokinase and glucokinase have different properties of their own and they inhibited by G6P and F6P. The hexokinase that is found in most tissues has a low Km value and they are strongly inhibited by G6P. Liver parenchymal cells and beta cells of the pancreas release glucokinase which is an iso-enzyme of hexokinase. Glucokinase catalyzes the conversion of glucose to G6P like other hexokinase but its S0.5 for glucose is considerably higher than the Km of glucose of hexokinase. Furthermore, glucokinase is much less sensitive to its product inhibition by G6P and its glucose saturation curve is sigmoidal that indicates its cooperativity.
  2. PFK-I is a regulatory enzyme of glycolysis. PFK-I is allosterically inhibited by citrate, ATP, and hydrogen ion concentration. PFK-I is allosterically activated by adenosine monophosphate (AMP), fructose 2,6-bisphosphate (F 2,6-BP).
  3. Pyruvate kinase is also a regulatory enzyme of glycolysis. Protein kinase A with the help of ATP inactivates the pyruvate kinase enzyme. Whereas phosphoprotein phosphatase with the help of water activates the pyruvate kinase.
Labels:

Comments

Post a Comment

If you want to know more about this topic or about related topics let me know in the comments

Popular posts from this blog

Discover the Kiwi: Nutritional Powerhouse and Health Champion

Are you missing out on a nutritional powerhouse? In this crazy busy world, our diets are often lacking in the nutrients we need for optimal health. Many people are struggling to find simple ways to boost their immune system and improve digestion and overall well-being. You may be thinking is there one food that can make a big difference without the need for complicated diets or supplements. Your current diet is failing you You might be eating fruits and vegetables and still not getting the full range of nutrients your body needs. You may be dealing with digestive issues, a weakened immune system or even skin problems and you think you’re eating healthy. The truth is not all fruits are created equal. Some are nutritional powerhouses that can fill gaps in your diet and provide targeted benefits—kiwi is one of them. The Kiwi—Your secret weapon for health The kiwi also known as kiwifruit is more than just a tangy sweet fruit. It’s a nutritional dynamo packed with vitamins, minera
Post a Comment
Read more

Iceberg Lettuce: The Hidden Gem in Your Bowl

Problem: The Misunderstanding of Iceberg Lettuce Iceberg lettuce must be one of the most criticized types of lettuce on the market today. It is often categorised as a lesser variety of lettuce than other varieties, such as romaine or spinach. Thanks to this misunderstanding, more and more people who understand the importance of healthy eating have omitted iceberg lettuce entirely from their diets. But is it true that iceberg lettuce is just sheets of cold crunch that do little more than pad out sandwiches and salad? Or does it possess qualities which one could not initially notice?  Agitation: The Need to Uncover the Truth We live in a world, where health has become a major concern for everyone, and even the food we eat is of great concern. This has made the diets based on nutrient-dense foods and making each meal count do away with such foods as iceberg lettuce. We may need this humble green, after all, not to make mistakes but to correct them. What if the iceberg lettuce contains som
Post a Comment
Read more

What is the role of hormones in obesity?

Obesity is an accumulation of an excessive amount of body fat, it is a complex disease. It is a medical problem that elevates the risk of different health problems and other diseases. Obesity is often measured by Body Mass Index (BMI). According to World Health Organization BMI greater than or equal to 30 is known as obesity. Though BMI has some limitations. Role of hormones in obesity: Role of Ghrelin This hormone influences eating behavior through direct or indirect effects on the brain. Neuropeptide-Y (NPY) is a hormone-like factor in the brain, that probably stimulates appetite. Although a number of signals can affect the ghrelin and leptin hormone, linked with NPY secretion to daily feeding pattern. Ghrelin sometimes called a hunger hormone. It is polypeptide in nature and produced in the stomach. Ghrelin level increases before a meal and quickly falls after food intake. The increase in ghrelin level appears to stimulate NPY, thus encouraging feeding. Role
1 comment
Read more