F215 Module 1: Control of Protein Synthesis, Body Plans and Apoptosis By Ms Cullen

Cyclic AMP (cAMP) cAMP in cells will activate some proteins by changing their 3D structure. An example of this is glycogen in muscle cells. Glycogen is broken down by the enzyme glycogen phosphorylase. It is synthesised by an enzyme called glycogen synthase. If glycogen was being broken down and made at the same time, it would be a waste of the cells energy.

cAMP To prevent this happening glycogen phosphorylase is activated by cAMP and inhibited by ATP and glucose- 6-P (when these are present glycogen will not need to be broken down to release more glucose for respiration). The cAMP causes the enzyme to change shape, revealing an active site to allow glycogen to be broken down. ATP and G-6-P have the opposite effect, changing shape to hide the active site.

Control of Protein Synthesis Each of our cells contains about 20,000 genes. Every cell contains the same genes, but not all cells use all these genes. Examples: Only white blood cells will produce antibodies and only certain skin cells will produce melanin. In a multicellular organism, each specialised cell will only use particular genes. This also explains how a zygote can differentiate to become specialised cells. In each cell type a particular set of genes are ‘switched on’ and others are ‘switched off’.

Control of Protein Synthesis Protein synthesis can be controlled at a genetic level, by altering the rate at which genes are transcripted. If transcription is increased then more mRNA will be produced. This, in turn will be used to make more proteins. In prokaryotes (eg bacteria) genetic control of protein production often involves operons.

The lac operon Even in a single-celled organism such as Escherichia Coli (E.coli), there are genes that are switched on and others that are switched off. E.coli will adapt to their environment by producing enzymes which will allow them to metabolise the medium they are growing on. E.coli produce 2 enzymes to help with the digestion and absorption of disaccharide lactose;  -galactosidase and lactose permease These enzymes will hydrolyse the disaccharide lactose into glucose and galactose.

The lac operon However, if E.coli is grown on a medium with only glucose it will not produce these 2 enzymes. The genes that control the protein synthesis for these 2 enzymes will be ‘switched off’. If we then transfered the same E.coli bacterium to a medium containing only disaccharide lactose, they would produce both  –galactosidase and lactose permease. The genes have been ‘switched on’. Lactose triggers this and is known as the inducer. The section of DNA within the bacterium that controls this is known as the lac operon. An operon is a length of DNA containing the base sequences that code for proteins known as structural genes.

The E. coli lac operon and its regulator gene.

How the lac operon works by stopping RNA polymerase binding to the promoter region when lactose is absent from the growth medium

How the lac operon works when lactose is present

Genes and body plans Some genes are responsible for the general structure of an organism (eg body parts head, abdomen etc). Proteins will control this body plan and ensure that all the parts grow in the correct place! Most of what we know about these genes has come about from the study of the fruit fly drosophila. Proteins which control body plans are coded for by genes known as homeotic genes. These homeotic genes have sequences known as homeobox sequences. In drosophila there are 2 homeotic gene clusters; 1 controls development of the head and anterior thorax; the other controls development of the posterior thorax and the abdomen.

Development in Drosophila Controlled by homeobox genes Segments Md, Mx and Lb become head. Segments T1-3 become thorax. Segments A1-8 become abdomen.

Genes and body plans Homeobox genes – control the development of the body plan of an organism, including the polarity (head and tail ends) and positioning of the organs. All segmented animals from annelids (segmented worms) to vertebrates have homeobox genes. Each homeobox gene contains 180 base pairs, which are known as the homeobox. These produce polypeptides about 60 amino acids long. Some of these polypeptides will initiate transcription, and so regulate the expression of other genes.

Genes and body plans Homeobox genes are arranged in clusters called Hox clusters. Nematodes have 1, drosophila 2 and vertebrates 4. Homeobox genes work in a similar way in most organisms, including plants and fungi.

Apoptosis - programmed cell death Sometimes it is necessary to get rid of cells as part of development. For example, a tadpole eventually has to lose it’s tail. In order of this to happen, tail cells will die and then be consumed by phagocytes. Another example of this is the development of fingers and toes. In an embryo the digits are connected. They only separate when cells in the connecting tissue undergo apoptosis. All cells contain genes that promote or inhibit apoptosis.

syndactyly handsembryonic hands

Series of events in apoptosis

Hayflick 1962 Since the 1900’s normal body cells were believed to be immortal. Leonard Hayflick came up with the idea that normal body cells divide a limited amount of times. He also proposed that cancer cells were immortal. This provides the basis of most modern research into cancer.