By Dr Ananya Mandal, MD
The metabolic pathways are complex and interdependent. With the changing environments the reactions of metabolism must be finely regulated to maintain a constant set of conditions within cells, a condition called homeostasis. Control of metabolic pathways also allows organisms to respond to signals and interact actively with their environments.
Concept of control and regulation
Regulation of metabolic pathways includes regulation of an enzyme in a pathway by increasing or decreasing its response to signals.
Control involves monitoring the effects that these changes in an enzyme’s activity have on the overall rate of the pathway. For example, an enzyme may show large changes in activity being highly regulated but if these changes have little effect on the flux of a metabolic pathway, then this enzyme is not involved in the control of the pathway.
Control of metabolism
- Coarse Control: control of the amount of an enzyme. This is a slow process as it involves protein synthesis.
- Fine Control: control of the activity of the enzyme. This is a fast process as it involves changing the activity of enzyme already available in the cells.
Levels of metabolic regulation
There are multiple levels of metabolic regulation.
For intrinsic regulation of metabolic pathways the reactions self-regulate to respond to changes in the levels of substrates or products. For example, a decrease in the amount of product can increase the metabolic pathway. This is called a feedback mechanism.
Extrinsic control involves a cell in a multicellular organism changing its metabolism in response to signals from other cells.
The signals approach the pathways via soluble messengers such as hormones and growth factors. These act by being detected by specific receptors on the cell surface.
These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins. For example, the hormone insulin from the beta cells of the pancreas is produced in response to rises in blood glucose levels. Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and glycogen.
Regulation of carbohydrate metabolism
Glucose homeostasis is a complicated interaction of metabolic pathways. It is vital for living organisms. These processes either increase or decrease the blood glucose concentration but they work together in order to maintain an optimal level.
Glucose is derived from carbohydrates taken in the diet. Carbohydrate is digested to the simple sugars: glucose, fructose and galactose. These sugars are absorbed in the intestine and transported to the liver via the portal vein. Thereafter the liver converts fructose and galactose into glucose. Rising levels of glucose in the blood stimulate the release of insulin from the b cells of the islets of Langerhans in the pancreas.
Insulin is the only hormone that reduces blood glucose levels, and it does this by activating the glucose transport mechanisms and glucose-utilizing metabolic pathways in different tissues of the body. Thus insulin down-regulates glucose forming pathways.
- uptake of glucose by muscle and adipose tissue
- glycogenesis (formation of glycogen from free glucose)
- protein synthesis
- gluconeogenesis (formation of glucose from aminoacids, fatty acids etc.)
- lipolysis (breakdown of fatty acids)
- proteolysis (breakdown of proteins)
- ketogenesis (formation of ketone bodies)
Disturbed glucose homeostasis is vital in causation of diseases like diabetes.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)