The cell in health and disease Flashcards
define homeostasis
Homeostasis is the process by which internal variables are kept within a normal range of values e.g. body temperature, blood glucose or blood pressure.
what happens when a stimulus changes/affects an internal variable from its normal range of values?
when a stimulus changes one of these internal variables, a receptor detects this change–> a control centre compares the change against a reference value/set point–> instructs effectors to make adjustments usually through negative feedback.
give an example of negative feedback
the body has a normal blood glucose range of 4.0 to 5.9 mmol/litre. If you eat a meal rich in carbohydrate, blood glucose will rise above its normal range. the rise in blood glucose is the stimulus. Unless the body’s glucose homeostatic mechanisms kick in, glucose will continue to rise and will make you very sick. This is what might happen in a patient who has type 1 diabetes who does not take their insulin. Normally, if blood glucose rises, the beta cells within the pancreas act as the sensor and control centre in that they detect this rise and release an effector, which is insulin. Insulin then binds to receptors in hepatocytes and skeletal muscle causing glucose to be taken up by these cells and stored as glycogen, restoring blood glucose to its normal range.
This negative feedback loop then stops too much insulin being produced and released, maintaining normoglycaemia or a normal blood glucose.
If on the other hand, blood glucose falls too low, alpha cells of the pancreas will detect this and will pump out the hormone, glucagon, which causes glucose to be released from the liver by conversion of stored glycogen to glucose.
Another way of maintaining homeostasis is by a positive feedback loop. define positive feedback and give an example of it.
POSITIVE FEEDBACK: where a variable change causes adjustment in the same direction as the initiating event.
BLEEDING:
If you are chopping your vegetables and the knife slips, you may be very unlucky and sever an artery in your hand. In this setting, the most immediate threat to your life is excessive blood loss. Less blood circulating means reduced blood pressure and
reduced perfusion of the brain and other vital organs. If perfusion is severely reduced, vital organs will shut down and the organs and person will die. Homeostatic mechanisms respond to this potential catastrophe by releasing substances from the injured blood vessel wall that begin the process of blood clotting. As each step of clotting occurs, it stimulates the release of more clotting factors. This accelerates the processes of clotting and seals off the damaged vessel. Clotting is contained in a local area based on the tightly controlled availability of these clotting proteins. This is an example of an adaptive, life-saving cascade of events.
HOMEOSTASIS SUMMARY
- Homeostasis is the maintenance of a physiological state within a narrow range which is compatible with life.
- Homeostatic systems are usually controlled by negative feedback but there are also examples of positive feedback loops.
- The components of a homeostatic system are the same for both loops and include a stimulus, a sensor, a control centre and an effector.
- Negative loops prevent an excessive response to a stimulus whereas positive loops
intensify the response to a stimulus until an end point is reached.
regarding cellular housekeeping, what is required for normal cell viability?
- in order to survive, a cell must be PROTECTED FROM THE ENVIRONMENT and it must receive adequate NUTRITION.
- for multicellular organisms, CELL COMMUNICATION is is essential–> extracellular signals determine whether a cell will live or die, whether it remains quiescent or whether it is stimulated to perform a specific function.
- Cell must also be able to GENERATE ENERGY and this is usually in the form of adenosine triphosphate (ATP).
- cells must be able to MOVE
- must be able to breakdown molecules (molecular catabolism) and renewal of senescent molecules.
give an overview of respiration in the mitochondria
At the cytoplasm, Glucose goes through glycolysis–> a metabolic pathway that cuts a 6 carbon glucose into two 3-carbon molecules known as pyruvate.
Pyruvate then enters the mitochondria and goes through the citric acid cycle/krebs cycle and the electron transport chain to produce ATP. This requires oxygen so is known as aerobic respiration.
1GLUCOSE + 4OXYGEN–> 32ATP + CO2 + H2O
If there’s not enough glucose, our cells can burn fatty acids in the mitochondria as a source of fuel- in a process called beta-oxidation. Mitochondria can only work with medium-sized fatty acids.
where has mitochondria evolved from?
Mitochondria evolved from prokaryotes which were engulfed by primitive eukaryotes. They contain their own DNA, which is always maternally inherited (because the ovum contributes the vast majority of cytoplasmic organelles to the fertilised zygote). Mitochondrial machinery is similar to that of bacteria.
what makes mitochondria similar to the nucleus?
They contain their own DNA, which is always maternally inherited (because the ovum contributes the vast majority of cytoplasmic organelles to the fertilised zygote). Mitochondrial machinery is similar to that of bacteria. Both nuclear and mitochondrial DNA contribute to the proteins of the mitochondria which means that mitochondrial diseases can be x-linked (caused by a mutation in a gene on the X- chromosome. A characteristic of X-linked inheritance is that fathers cannot pass X-
linked traits to their sons), autosomal (caused by a gene abnormality affecting any chromosome apart from the sex chromosomes) or maternally inherited (caused by a mutation in the mitochondrial DNA). Mitochondria undergo self replication in a manner which is similar to bacterial cell division.
where is the site of ATP synthesis?
The mitochondria’s intermembrane space
Rapidly growing cells can upregulate glucose and glutamine uptake, to produce
intermediates so that lipids, proteins and nucleic acids can be produced instead of ATP in some circumstances.
The intermembrane space is the site of ATP synthesis. As a by product, reaction oxygen species are produced. Thermogenin which is plentiful
in brown fat resides in the inner membrane and can generate heat. We will see in later lectures that the sensors of cell damage are found in mitochondria which can initiate and regulate apoptosis (programmed cell death).
what can cause damage to the mitochondria?
Mitochondria can be damaged by toxins, ischaemia or trauma causing ATP generation to fail through loss of the proton gradient.
We already said that if there’s not enough glucose, our cells can burn fatty acids in
the mitochondria as a source of fuel - in a process called beta oxidation but mitochondria can only work with medium sized fatty acids. what organelle can chop up long fatty acids and transform them into medium sized ones? what is a side effect to the process?
peroxisome
This process generates dangerous hydrogen peroxide, but the peroxisome has an enzyme called peroxidase–> can safely convert the hydrogen peroxide into water and oxygen.
Haem which is a component of haemoglobin is also made in mitochondria.
To survive, all cells must be able to dispose of waste - what are the organelles that help to do this?
LYSOSOMES AND PROTEASOMES.
DESCRIBE the lysosome and how it works
membrane bound organelles which contain enzymes that can digest cell constituents.
Lysosomes contain over 40 different enzymes called acid hydrolases which include proteases, lipases and nucleases, all of which work best at a pH less than 5. Material arrives at the lysosome via 1 of 3 pathways – via an endosome, phagosome, or autophagosome. In heterophagy, cells take up material from outside the cell by using processes such as receptor-mediated endocytosis and pinocytosis or a specialized process such as phagocytosis. Endosomes then fuse with lysosomes. In autophagy, membrane-bound vesicles are formed within the cell by engulfing material such as proteins, lipids and organelles. After formation, these autophagosomes fuse with lysosomes. Formation of lysosomes requires translation of lysosomal proteins in the endoplasmic reticulum and their sorting to the correct vesicles in the Golgi complex.
Phagosomes form most commonly in neutrophils and macrophages, which ingest foreign material. We will encounter this again when we discuss acute inflammation
later in the year.
