Metabolism Regulation

Metabolic pathways need to be regulated to ensure that organisms function efficiently. Using appropriate examples discuss the different ways in which metabolic pathways are regulated and the possible consequences if this regulation malfunctions.

Inside all living organisms, a series of constant chemical reactions are carried out to ensure the survival of the organism, these processes are known as metabolism.  Metabolic reactions are generally divided into two categories.  Catabolism, using oxidative reactions, breaks down complex molecules into simpler molecules to produce adenosine triphosphate (ATP) and reducing power (NADH, FADH2 and NADPH).  These products supply energy for all cell activity and for biosynthesis (anabolic processes).    The second category of metabolism, anabolism, uses the intermediates of catabolism to produce complex molecules from simpler molecules by way of reductive reactions.

Metabolic regulation is vital to maintain stable conditions within the cell, homeostasis.  There are a number of ways in which metabolic regulation is achieved; some of these methods are integrated in the metabolic processes, for example, metabolic pathways have committed steps which occur early in the pathway with the aim of dictating the rate of metabolism and to ensure the remainder of the pathway takes place.

Each of the chemical reactions that occur in metabolism is catalysed by specific enzymes.  Enzymes also act as mechanisms that regulate and coordinate the activity in the cell.  The addition or removal of a phosphate group can activate or inhibit enzymes.  An allosteric enzyme attaches itself to the allosteric site to change the shape of the enzyme.  ATP and ADP are generic molecules that can be allosteric. 

Feedback inhibition regulates enzyme activity by means of utilising the end product.  This method is employed when the substance the enzyme has produced has accumulated to an amount that is adequate; the production of that substance is then discontinued.

The production of zymogens is also an enzyme regulator.  A zymogen is an enzyme that has been produced in an inactive form, when the enzyme is required for catalysis it is converted by proteolysis in to an active form.

Glycolysis is just one of the many pathways that provide cells with energy.  It begins with the degradation of glucose. 

There are three enzymes in particular that regulate this pathway.  The first enzyme is Hexokinase; it is involved in the phosphorylation of glucose to produce glucose-6-phosphate.  It inhibits the pathway where high levels of glucose-6-phosphate are present and can also add force to the inhibition of phosphofructokinase, the second regulatory enzyme.  There are two allosteric effectors at this phase; AMP and fructose 2, 6-bisphosphate.  ATP and AMP compete for the allosteric effector site on the phosphofructokinase enzyme.  Therefore high levels of AMP will activate the pathway.  The last enzyme that controls this pathway is pyruvate kinase, fructose 1, 6-bisphosphate is the molecule that may enhance enzymatic activity.  High levels of ATP will inhibit this enzyme.

Glycolytic mutations are uncommon as the components that are responsible in maintaining functionality of this pathway are very efficient.  However, there are some errors that may occur; such as Pompe disease or glycogen storage disease type VII.  A defect in the level of the muscular isoenzyme of phosphofructokinase is the cause of this hereditary disease.  Glucose degradation is hindered during exercise and increases glucose-6-phosphate levels. 

As inadequate amounts of glucose are consumed from the diet and glycogen stores are effortlessly depleted, the body is required to generate supplementary glucose.  Gluconeogenesis is involved in anabolically producing glucose from pyruvate molecules.  The three enzymes used in glucose break down are replaced with four enzymes that are unique to Gluconeogenesis.  These are; glucose-6-phosphatase, fructose 1, 6-bisphosphatase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase. 

Pyruvate carboxylase, a hydrolase enzyme, is located in the mitochondrial matrix and converts pyruvate into oxaloacetate.  A deficiency of this enzyme may lead to an increased level of lactate and lactic acidosis.  Phosphoenolpyruvate carboxylase reverses the pyruvate kinase reaction in glycolysis.  The rate of metabolism is controlled by fructose 1, 6-bisphosphase, this enzyme is inhibited by elevated levels of AMP and activated by low levels of ATP.  Lacking levels of this enzyme may bring about hypoglycemia, low blood glucose level.  Glucose-6-phosphate is unable to diffuse out of the cell; consequently gluconeogenesis ends at Glucose-6-phoshate.  Glucose-6-phoshase is important in configuring free glucose when it is able to leave the cell. 

Gluconeogenesis is also controlled by hormones, primarily glucagon and insulin.  Glucagon is produced in the pancreas; it is released into the blood when blood sugar levels decrease.  Phosphoenolpyruvate carboxylase levels are increased and gluconeogenesis is initiated, preventing hypoglycemia.  Insulin responds to high glucose levels and causes the cells of the liver, muscle and adipose to obtain glucose from the blood and store it as glycogen and discontinue fat utilisation as an energy source.  Disturbance of insulin can cause numerous problems such as; diabetes mellitus (type I and II) which is a very a common metabolic syndrome which can lead to other complications, for example, vascular disease. 

Metabolism is an intricate system that requires various mechanisms to maintain constancy.  This essay has addressed only a tiny fraction of the enzymatic reactions and how metabolism is regulated.  Some of the methods are integrated in the pathway, for example, committed steps and pathways in eukaryotes are found in specific cellular locations.  In order for the cell to survive, every molecule conversion and branch point in the pathway must be carefully regulated.  Metabolites must be cautiously routed into anabolic or catabolic pathways for degradation or biosynthesis.

Without these mechanisms, the cell would surely die.  However, the ever increasing understanding of cell activity, in particular, metabolic pathways, improvements are being made in biology, biotechnology, pharmacology and nutrition to combat possible metabolic diseases.