End-product inhibition means that an enzyme in a pathway is inhibited by the product of that pathway. This prevents a cell over-producing a
Competitive inhibitor
The inhibition produced by a competitive inhibitor is negated by high concentrations of substrate.
no inhibitor
no inhibitor
with inhibitor
with more inhibitor with inhibitor
with more inhibitor
Substrate concentration
Initial rate of reaction
Non-competitive inhibitor
Substrate concentration
Initial rate of reaction
substrate competitive
inhibitor
active site
substrate
active site
inhibitor site non-competitive inhibitor
substance it does not need at the time. Many products may be needed by the cell at a specifi c time or in specifi c amounts and over-production not only wastes energy but may also become toxic if the product accumulates.
In an assembly-line reaction, such as those described in Figure 7.23, each step is controlled by a diff erent enzyme. If the end-product begins to accumulate because it is not being used, it inhibits an enzyme earlier in the pathway to switch off the assembly line. In most cases, the inhibiting eff ect is on the fi rst enzyme in a process, but in other cases it can act at a branch point to divert the reaction along another pathway.
When the end-product starts to be used up, its inhibiting eff ect reduces, the inhibited enzyme is reactivated and production begins again. This is an example of negative feedback (see page 154).
End-product inhibition may be competitive or non-competitive.
Competitive inhibition will only work if the product is a similar shape to the normal substrate and there can be an induced fi t of the product or inhibitor onto the enzyme. In most cases, the product will be a diff erent
Competitive inhibitors Non-competitive inhibitors
• structurally similar to the substrate molecule
• occupies and blocks the active site
• if concentration of inhibitor is low, increasing the concentration of substrate will reduce the inhibition
• examples include:
– oxygen, which competes with carbon dioxide for the active site of ribulose bisphosphate carboxylase in photosynthesis – disulfi ram, which competes with acetaldehyde for the active
site of aldehyde dehydrogenase
• structurally unlike the substrate molecule
• binds at a site away from the active site, reduces access to it
• if concentration of substrate is low, increasing the concentration of substrate has no effect on binding of the inhibitor so inhibition stays high
• examples include:
– cyanide and carbon monoxide, which block cytochrome oxidase in aerobic respiration, leading to death
Table 7.2 Comparing competitive and non-competitive inhibitors.
initial substrate
intermediate A enzyme 1
enzyme 2
enzyme 3 intermediate B
The end-product inhibits the enzyme catalysing the first reaction in the series, so all the subsequent reactions stop.
end-product
initial substrate
intermediate A
intermediate B
The end-product inhibits an enzyme in the pathway, which causes a different enzyme to come into play and the pathway is diverted down a different route.
end-product 1
intermediate C
end-product 2
Figure 7.23 End-product inhibition.
7 NUCLEIC ACIDS AND PROTEINS 189 shape and therefore this has to be non-competitive inhibition. In this case,
the enzyme is known as an allosteric enzyme, the product is called an allosteric inhibitor and the place where it binds to the enzyme is called the allosteric site (Figure 7.24).
11 Outline the four levels of protein structure.
12 List three differences between fi brous and globular proteins.
13 List four functions of proteins.
14 Outline what is meant by ‘activation energy’.
15 Explain how the induced-fi t model differs from the lock-and-key hypothesis for enzyme action.
End-of-chapter questions
1 The components of a nucleosome are:
A ribosomal RNA and DNA B 8 histone proteins and DNA
C 8 histones proteins in a ball + 1 further histone
D 9 histone proteins and DNA (1)
2 Which of the following statements is correct about the structure of DNA?
A The purine base cytosine is linked to the pyrimidine base guanine through three hydrogen bonds.
B The sugar–phosphate strands are antiparallel and linked by complementary base pairing.
C The bases are linked to each other through a 3'–5' linkage.
D Complementary base pairing of guanine with cytosine and adenine with uracil
means that the two sugar–phosphate strands lie parallel. (1)
Figure 7.24 Allosteric control. Allosteric inhibitors prevent the active site functioning.
substrate
products active site
allosteric site
allosteric non-competitive inhibitor
3 Which of the following statements is correct about DNA replication?
A The enzymes DNA ligase and RNA primase can be found on the lagging strand.
B Okazaki fragments are produced by DNA polymerase I and DNA polymerase III on the leading strand.
C On the lagging strand, the RNA primer is synthesised by RNA primase and then converted into a DNA strand with the enzyme DNA polymerase III.
D The enzyme DNA polymerase III uses deoxynucleoside triphosphates to build a
new DNA strand only on the leading strand. (1)
4 Which of the following statements is correct about transcription?
A The enzyme RNA polymerase moves along the antisense strand in a 3' → 5' direction.
B The sequence of bases in the strand of RNA being synthesised is the same as the sequence of bases in the sense strand of DNA.
C In eukaryotic cells, exons are removed from the primary RNA in the nucleus to make mature RNA.
D Messenger RNA is synthesised by RNA polymerase in a 3' → 5' direction. (1)
5 Which of the following statements is correct about translation?
A Ribosomes that are free in the cytoplasm synthesise proteins that are primarily for lysosome manufacture and exocytosis.
B Ribosomes are made of two subunits and mRNA binds to the larger one.
C On the larger ribosome subunit there are three binding sites that can be occupied by tRNA molecules.
D During polypeptide synthesis, the ribosome moves along the mRNA strand in a
3' → 5' direction until it reaches a stop codon. (1)
6 Which of the following statements is correct about protein structure?
A There are four levels of protein structure. The primary level is held together by covalent and hydrogen bonding.
B Enzymes have an active site that is a three-dimensional structure produced by secondary level folding of the protein.
C The α helix and β pleated sheet are both types of tertiary level folding.
D Both tertiary and quaternary level proteins can form conjugated proteins. (1)
7 Which of the following statements is correct about enzymes?
A Most enzymes use the lock-and-key model of substrate interaction as it is the most stable.
B In allosteric control of metabolic pathways, a product within the pathway can act as a non-competitive inhibitor of an enzyme earlier in the pathway.
C Increasing the concentration of substrate has no eff ect on the rate of a reaction being inhibited by a competitive inhibitor.
D Competitive inhibitors bind to an allosteric site and alter the shape of the active site. (1)
7 NUCLEIC ACIDS AND PROTEINS 191
8 Explain the process of translation. (9)
9 Explain how control of metabolic pathways can be brought about by end-product inhibition. (6)
10 It had always been assumed that eukaryotic genes were similar in organisation to prokaryotic genes.
However, modern techniques of molecular analysis indicate that there are additional DNA sequences lying within the coding region of genes. Exons are the DNA sequences that code for proteins while introns are the intervening sequences that have to be removed. The graph shows the number of exons found in genes for three diff erent groups of eukaryotes.
a Calculate the percentage of genes that have fi ve or fewer exons in mammals. (1) b Describe the distribution of the number of exons and the percentage of genes in D. melanogaster. (2) c i Compare the distributions of the number of exons found in genes of S. cerevisiae and in mammals. (2) ii Suggest one reason for the diff erences in the numbers of exons found in genes of S. cerevisiae and
in mammals. (1)
100
Percentage of genes
80 60 40 20 0 40 30 20 10 0 20 15 10 5
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 <30<40<60>60 Number of exons
source: Benjamin Lewin (1999) Genes Vll, OUP, p. 55
Mammals
Drosophila melanogaster (fruit fly) Saccharomyces cerevisiae (a yeast)