Question

You are faced with an imminent threat to your safety and decide to RUN for your life! As
part of the flight/fight response activation of your HPA axis lead to an increase in the
hormone adrenalin. Discuss how adrenalin binding to a receptor on hepatocyte cells can
ultimately lead to the breakdown of glycogen. Your answer should include details of the
receptor activation at the plasma membrane, signal transduction in the cytoplasm leading to
activation of glycogen phosphorylase.

Note; please explain briefly, like long answer. questions is 20 Mark's weightage so dnt finished it short.

-You are faced with an imminent threat to your safety and decide to RUN for your life!

-As part of the flight/fight response activation of your HPA axis lead to an increase in the
hormone adrenalin.

-Discuss how adrenalin binding to a receptor on hepatocyte cells can
ultimately lead to the breakdown of glycogen.
-Your answer should include details of the
receptor activation at the plasma membrane, signal transduction in the cytoplasm leading to
activation of glycogen phosphorylase.

Answer 1

The adrenal medulla is actually a modified part of the sympathetic nervous system. It consists of modified postganglionic sympathetic neurons. Unlike ordinary postganglionic sympathetic neurons, those in the adrenal medulla do not have axons. Modified postganglionic sympathetic neurons of adrenal medulla release hormones directly into the blood rather than releasing a neurotransmitter, the cells of the adrenal medulla secrete hormones. The hormon producing cells are called chromaffin cells. the two major hormones synthesized by the adrenal medulla are epinephrine (or adrenaline) and norepinephrine (or noradrenaline). The chromaffin cells of the adrenal medulla secrete an unequal amount of these hormones-about 80% epinephrine and 20% norepinephrine. Both of these hormones are synthesized from the amino acid tyrosine. Adrenalin and noradrenalin are collectively known as catecholamines.

In emergency or stress condition (in this case fear and run), impulses from the hypothalamus stimulate sympathetic preganglionic neurons, which in turn stimulate the chromaffin cells to secrete adrenalin and noradrenalin. During these conditions these hormones greatly augment the fright, fight and flight response; hence called as emergency hormone or hormones of fight or flight.

By increasing heart rate and force of contraction, adrenalin and noradrenalin increase the output of the heart, which increases systolic blood pressure. They also increase blood flow to the heart, liver, skeletal muscles and adipose tissue ; dilate airways to the lungs; and increase blood levels of glucose and fatty acids.

In this situation,the ultimate result of the HPA activation is increased levels of cortisol in the blood. Thus, glucose will be released into the bloodstream in order to facilitate the flight or fight response. During chronic stress, changes occur to the neurons in the PVN(paraventricular nucleus) and other stress areas in the brain resulting in increased sustained activation of the HPA axis and subsequent release of adrenalin from the adrenal medulla in order to cope with the stress and high cortisol production.

Adrenalin, along with another hormone called glucagon, is responsible for the breakdown of glycogen in liver cells. Glycogen is a form of energy storage in animals. Adenalin binds to a receptor at the outside of a liver cell causing a conformational change to occur. This change means that a G protein can now bind. Consequently adenylate cyclase and ATP can bind to the complex. Adenylate cyclase breaks down ATP into a second messenger molecule called cyclic AMP, commonly referred to as cAMP. The second messenger then causes the activation of a protein kinase which activates phosphorylase. Phosphorylase is an enzyme which catalyzes the breakdown of glycogen to glucose.

The signal molecules adrenalin and glucagon bind to specific 7TM receptors in the plasma membranes of muscle and liver cells, respectively. Adrenalin binds to the beta-adrenergic receptor in muscle, whereas glucagon binds to the glucagon receptor. These binding event activate the alpha subunit of the heteromeric Gs protein. A specific external signal has been transmitted into the cell through structural changes, first in the receptor and then in the G protein. The GTP-bound form of the alpha subunit of Gs activates adenylate cyclase, a transmembrane protein that catalyzes the formation of the secondary messenger cyclic AMP from ATP. The elevated cytosolic level of cyclic AMP activates protein kinase A through the binding of cyclic AMP to the regulatory subunits, which then dissociate from the catalytic subunits. The free catalytic subunits are then get activated. Protein Kinase A phosphorylates the beta subunit of phosphorylase kinase, which subsequently activates glycogen phosphorylase.The cyclic AMP cascade highly amplifies the effects of hormones. Hence, the binding of a small number of hormone to cell-surface receptors leads to the release of very large number of sugar units. Indeed, the amplification is so large that much of the stored glycogen would be mobilized within seconds.

Adrenalin can also elicit glycogen degradation in the liver. However, in addition to binding to the beta-adrenergic receptor, it binds to the 7TM alpha-adrenergic receptor, which then activates phospholipase C and hence, initiates the phosphoionositide cascade. The consequent rise in the level of ionositol-1,4,5-triphosphate induces the release of Calcium ions from the endoplasmic reticulum.

In this way, adrenalin binding to a receptor on hepatocyte cells can ultimately lead to the breakdown of glycogen.