Glucose Metabolism Overview and Regulation

Also known as the Hexose Monophosphate Shunt or Phosphogluconate Pathway. It's an alternative way to oxidize glucose without directly using or making ATP.

The pentose phosphate pathway is divided into two stages, one that's reversible and one that's not.

This phase of the pentose phosphate pathway produces NADPH and it's not reversible.

NADPH is a key molecule involved in building fatty acids, cholesterol, and steroid hormones; breaking down certain amino acids; and protecting cells from damage.

The pentose phosphate pathway provides a route for 5-carbon and 6-carbon sugars to enter glycolysis.

The process of creating glucose from non-carbohydrate sources, such as pyruvate, lactate, glycerol, and certain amino acids.

Certain amino acids are broken down into pyruvate or oxaloacetate, which are intermediates in the gluconeogenesis pathway.

Glycerol, produced from the breakdown of fats, is a direct precursor for gluconeogenesis.

Glucose 6-phosphatase catalyzes the final step of gluconeogenesis, releasing free glucose into the bloodstream.

Pyruvate carboxylase converts pyruvate to oxaloacetate, a key intermediate in the gluconeogenesis pathway.

Phosphoenolpyruvate carboxykinase converts oxaloacetate to phosphoenolpyruvate, another key intermediate in gluconeogenesis.

Glycolysis and gluconeogenesis are regulated to ensure that one pathway is more active than the other depending on the cell's needs.

Gluconeogenesis is primarily active in the liver, which releases newly synthesized glucose into the bloodstream to meet the body's energy demands.

This is the first irreversible reaction in glycolysis, preventing glucose from leaving the cell, and involves phosphorylation by hexokinase.

This is an isozyme of hexokinase found specifically in the liver, with a higher Km for glucose, meaning it only becomes saturated at higher glucose concentrations.

Glucokinase is not inhibited by glucose-6-phosphate, allowing the liver to store excess glucose as glycogen when blood glucose levels are high.

The rate of glucose entry into a cell depends on the number of glucose transporters on its surface and their affinity for glucose.

These are proteins that facilitate the transport of glucose across cell membranes but differ in their affinity for glucose and response to insulin.

The liver's high concentration of glucose transporters allows it to efficiently take up and process glucose for storage.

This enzyme catalyzes the second irreversible reaction in glycolysis, converting fructose-6-phosphate to fructose-1,6-bisphosphate.

The activity of phosphofructokinase-1 is regulated by various factors, including allosteric effectors, such as ATP, ADP, and citrate, and covalent modification through phosphorylation.

cAMP increases in cells primarily due to the actions of glucagon and epinephrine, which stimulate gluconeogenesis when more glucose is needed.

F2,6BP phosphatase is stimulated, leading to a decrease in F2,6BP concentration within the cell.

Hexokinase, a glycolytic enzyme, acts as a transcriptional repressor in yeast cells under high glucose levels, controlling gene expression.

Mammals have four isoforms of hexokinase, one of which is highly active in cancer cells, while another interacts with mitochondria to coordinate glycolysis with mitochondrial functions.

Glyceraldehyde-3-phosphate dehydrogenase (Gly-6) and enolase (Gly-9) can bind to DNA and act as regulators of gene expression, connecting glycolysis to processes like cell division and programmed cell death.

Phosphoglucoisomerase (PGI) plays a role in cell movement and migration during cancer metastasis, promoting cell proliferation and invasion.

The Cori Cycle is a metabolic pathway that operates during exercise, transferring lactate produced by muscle cells to the liver for conversion into glucose, which can then be returned to the muscles as fuel.

The Cori Cycle helps the body adapt to fluctuating energy demands in skeletal muscle, allowing for efficient use of fuel between resting and active states.

The committed step of glycolysis where fructose-6-phosphate is converted to fructose-1,6-bisphosphate. It is regulated by energy charge (ATP, AMP ratio) and citrate.

A molecule that inhibits the enzyme phosphofructokinase-1 (PFK-1), decreasing the rate of glycolysis. This feedback inhibition prevents the accumulation of excess citrate.

A molecule produced by the liver during fasting or starvation. Glucagon promotes the conversion of stored glycogen to glucose, raising blood sugar levels.

The process of synthesizing glucose from non-carbohydrate sources like pyruvate, lactate, or glycerol. This process occurs mainly in the liver and kidney.

Three irreversible steps in glycolysis that are bypassed in gluconeogenesis with different enzymes. These include the conversion of glucose to glucose-6-phosphate, fructose-6-phosphate to fructose-1,6-bisphosphate, and phosphoenolpyruvate to pyruvate.

A reversible reaction that can proceed in both directions catalyzed by the same enzyme.

The process of breaking down glucose into pyruvate, releasing energy in the form of ATP. This occurs in the cytoplasm of cells.

It is activated by fructose-1,6-bisphosphate, a feed-forward activation mechanism. This increases the rate of glycolysis, especially when glucose is abundant.

A metabolic pathway that produces NADPH and the precursor for nucleotide biosynthesis (ribose-5-phosphate). It occurs in two phases: an oxidative irreversible phase and a non-oxidative reversible phase.

The first phase of the Pentose Phosphate Pathway. This step involves the oxidation of glucose-6-phosphate using NADP+ as an electron acceptor, generating NADPH and CO2 as byproducts.

The second phase of the Pentose Phosphate Pathway. It involves a series of reversible reactions that allow for the conversion of various sugar phosphates back to glucose-6-phosphate, utilizing enzymes like transketolase and transaldolase.

An enzyme involved in the Non-Oxidative Reversible Phase of the PPP. It catalyzes the transfer of a 2-carbon fragment between sugar phosphates, facilitating conversions.

An enzyme involved in the Non-Oxidative Reversible Phase of the PPP. It catalyzes the transfer of a 3-carbon fragment between sugar phosphates.

A key role of the Pentose Phosphate Pathway in red blood cells is to maintain a high level of NADPH, which is required by the glutathione reductase enzyme. This enzyme converts oxidized glutathione (GSSG) back to its reduced form (GSH), which is crucial for combating reactive oxygen species (ROS).

The first step in the oxidative irreversible phase of the PPP, catalyzed by glucose-6-phosphate dehydrogenase. This reaction is regulated by feedback inhibition from NADPH and is induced by increased insulin/glucagon ratio after a high carbohydrate meal.

The enzyme catalyzing the rate-limiting step in the PPP. Its activity is regulated by feedback inhibition from its product NADPH and is induced by increased insulin/glucagon ratio after a high carbohydrate meal.