Twitter Icon Facebook

   Anatomy

   Biochemistry

   Boards

   Book Store

   Cardiovascular

   Endocrinology

   Financial Articles

   Gastrointestinal

   Genitourinary

   Gynecology

   Healthy Living

   Hematology

   How to Section

   Infectious    Diseases

   Musculoskeletal

   Neurological

   Nutrition

   Obstetrics

   Pharmacology

   Physical
   Examination

   Physiology

   Psychiatry

   Pulmonary

   Renal

   Rheumatology

   Useful Links

   Home

   Resources for...

 Medical Students

   YouTube

      Google Analytics Alternative

    

    

Glycolysis

Biochemistry || Regulation || Overview || Related Articles ||
References and Resources || Leave a Comment || Search

Biochemistry





Glycolysis is the biochemical pathway that strips glucose of its energy. It starts with glucose and ends with pyruvate (see image below). Pyruvate is converted to acetyl-CoA, which can be stored as fat, or further metabolized in the citric acid cycle. The fate of pyruvate depends on the energy needs of the cell.

The net yield of energy from glycolysis is 2 adenosine triphosphates (ATP) and 2 nicotinamide adenine dinucleotide (NADH) molecules per glucose "burned" by the pathway. Each NADH molecule from glycolysis eventually generates 1.5 ATPs from the electron transport chain. Therefore, a total of 5 ATP molecules are produced per molecule of glucose consumed by glycolysis.

The net "energy" used or created (in the form of ATP or NADH) are shown next to the respective steps below:

Glycolysis

Top

Regulation

Glycolysis is regulated at several steps in order to ensure that glucose molecules are used appropriately by the cell. The first point of regulation is at the conversion of glucose to glucose-6-phosphate (G6P). This reaction is catalyzed by an enzyme known as hexokinase. This enzyme is inhibited by its own product - G6P. This is known as "feedback inhibition". Once glucose is converted to G6P it becomes "trapped" inside the cell. Therefore, when there are adequate G6P levels any particular cell can shut off the flow of glucose into glycolysis so that it can be sent to other cells that may need it.

Phosphofructokinase 1
(PFK1) is the key
regulatory enzyme in the
glycolytic pathway.
The second, and key, regulatory point of glycolysis is at the enzyme phosphofructokinase-1 (PFK1). PFK1 converts fructose-6-phosphate (F6P) to fructose-1,6-bisphosphate. It is inhibited by ATP and citrate, and activated by ADP, AMP, and fructose-2,6-bisphosphate (note that this is a different molecule than fructose-1,6-bisphosphate). In other words, when the body is in an energy depleted state (low levels of ATP and high levels of ADP and AMP) glycolysis is activated; under conditions of high energy (high levels of ATP) glycolysis is inhibited. It is important to regulate the enzyme PFK1 closely because once F6P is converted to fructose-1,6-bisphosphate it MUST continue down the glycolytic pathway.

Side note: fructose-2,6-bisphosphate is produced by the enzyme phosphofructokinase-2 (PFK2) and degraded by the enzyme fructose bisphosphatase-2 (FBPase2). PFK2 becomes active under conditions of satiety (ie: well fed states in which lots of glucose/sugar is being absorbed from the gut). When PFK2 is active the concentration of fructose-2,6-bisphosphate increases. This activates PFK1 and increases the activity of the glycolytic pathway.

The final point of regulation is at the enzyme pyruvate kinase. This enzyme converts phosphoenolpyruvate into pyruvate. It is inhibited by ATP, acetyl-CoA, and long chain fatty acids, which are all markers of high energy levels.

In general, the overall regulation of glycolysis is related to how much energy the cell has. In energy rich states (ie: high ATP and low ADP/AMP) the cell slows glycolysis so that it can store glucose for use at a latter time. In energy depleted states (ie: low ATP and high ADP/AMP) the rate of glycolysis increases so that more energy can be formed by "burning" more glucose molecules per unit time.

Top

Overview

Glycolysis breaks down glucose molecules. In the process the energy rich molecules ATP and NADH are formed. It is regulated at several enzymatic steps, most importantly at the enzyme phosphofructokinase-1. Pyruvate can be further metabolized to acetyl-CoA.

Top

Related Articles

- Krebs cycle (aka: citric acid cycle)

- Electron transport chain

Top

References and Resources

(1) Nelson DL, Cox MM. Lehninger Principles of Biochemistry. Fifth Edition. New York: Worth Publishers, 2008.

(2) Champe PC. Lippincott's Illustrated Reviews: Biochemistry. Second Edition. Lippencott-Ravens Publishers, 1992.

(3) Le T, Bhushan V, Grimm L. First Aid for the USMLE Step 1. New York: McGraw Hill, 2009.

Top

HTML Comment Box is loading comments...

Top

Search VirtualMedStudent.com

Loading
An enzyme is a protein molecule that helps a chemical reaction occur. Nearly every reaction in the body is catalyzed by an enzyme.
Normally an NADH molecule produces 2.5 ATP (if formed by the citric acid cycle). The decreased yield seen in glycolysis is because the NADH must be transported from the cytosol of the cell (the location of glycolysis) to the mitochondrial matrix (the location of the electron transport chain). This transportation requires energy in the form of 1 ATP per NADH.