Proteins
No other family of biomolecules has such a wide variety of functions as proteins: a collagen fibre, an antibody and a digestive enzyme are, at heart, the same kind of polymer folded in different ways. This section explains how a linear sequence of amino acids ends up determining a precise three-dimensional shape, and why that shape is, quite literally, the function.
Amino acids and the peptide bond
Spider silk, the keratin in hair and haemoglobin have opposite mechanical and chemical properties, yet when they are hydrolysed in the laboratory they all break down into amino acids drawn from the same set of 20 types. Even the whey protein in a glass of Irish milk or the protein in a Wicklow hill farm's wool is built from them. What common architecture do these building blocks share that allows them to join together and produce such different functions?
What are amino acids and how many different types make up the proteins of living organisms? State which chemical groups all amino acids share and which endows each one…
What are amino acids and how many different types make up the proteins of living organisms? State which chemical groups all amino acids share and which endows each one with its particular properties.
Name four different functions of proteins in living organisms and give a specific example of a protein for each function.
Name four different functions of proteins in living organisms and give a specific example of a protein for each function.
What is a peptide bond? State between which chemical groups of the amino acids it forms and what molecule is released in the reaction.
What is a peptide bond? State between which chemical groups of the amino acids it forms and what molecule is released in the reaction.
The four levels of structure
Look at the diagram of the levels of protein organization, numbered from 1 to 4. Name each level, briefly describe its main feature, and give an example of a protein…
Look at the diagram of the levels of protein organization, numbered from 1 to 4. Name each level, briefly describe its main feature, and give an example of a protein that exhibits level 4.
Functional adult hemoglobin ($\text{HbA}$) is a soluble heterotetramer. In sickle cell anemia, a point mutation in the $\beta$-globin gene replaces a glutamic acid with…
Functional adult hemoglobin ($\text{HbA}$) is a soluble heterotetramer. In sickle cell anemia, a point mutation in the $\beta$-globin gene replaces a glutamic acid with valine at position 6 of the polypeptide chain ($\text{HbS}$), causing deoxyhemoglobin to polymerize into long insoluble fibers that deform erythrocytes.
- a) Based on the chemical properties of the side chains of both amino acids, justify why this change in primary structure alters the conformation and solubility of the protein, and indicate what type of weak molecular interactions stabilize these fibers.
- b) In a genetic screening, two alternative mutations are detected at that same codon 6 of $\beta$-globin:
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Variant A: glutamic acid is replaced by aspartic acid ($\text{Glu6Asp}$).
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Variant B: glutamic acid is replaced by leucine ($\text{Glu6Leu}$).
Predict with reasoning which of these two variants will maintain a biological function virtually identical to healthy $\text{HbA}$ and which will cause pathological aggregation similar to sickle cell anemia.
Denaturation: when shape is lost
When you squeeze lemon juice onto warm milk, the soluble casein precipitates into dense lumps, and when you fry an egg for a full Irish breakfast the liquid, transparent white turns opaque and solid in a few seconds. Why does a change in the surroundings alter the properties of a protein so radically without breaking its chain of amino acids?
Haemoglobin loses its three-dimensional shape if the temperature or pH strays too far from normal values. What is this process called, which bonds are broken, and what…
Haemoglobin loses its three-dimensional shape if the temperature or pH strays too far from normal values. What is this process called, which bonds are broken, and what consequence does it have on the protein's function?
Enzymes: biological catalysts
A commercial hydrogen peroxide solution takes months to break down in its bottle, but if you add a drop of blood or a piece of raw potato, the release of oxygen gas is instant and turbulent. How do cells manage to speed up a chemical reaction millions of times without being used up in the process?
What is an enzyme? Explain how it accelerates a chemical reaction with reference to activation energy and the enzyme-substrate complex.
What is an enzyme? Explain how it accelerates a chemical reaction with reference to activation energy and the enzyme-substrate complex.
In a biochemistry laboratory, the thermal stability of an intracellular human enzyme is investigated. Aliquots of the enzyme are incubated for 20 minutes at four…
In a biochemistry laboratory, the thermal stability of an intracellular human enzyme is investigated. Aliquots of the enzyme are incubated for 20 minutes at four different temperatures ($15\ \text{°C}$, $37\ \text{°C}$, $45\ \text{°C}$, and $70\ \text{°C}$). Each sample is then divided into two fractions:
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Fraction 1: its catalytic rate is measured immediately at the same temperature at which it was incubated.
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Fraction 2: the sample is returned to $37\ \text{°C}$, kept for 15 minutes, and its catalytic rate is then measured at $37\ \text{°C}$.
The results show that Fraction 1 has optimal activity at $37\ \text{°C}$, very low activity at $15\ \text{°C}$, and zero activity at $70\ \text{°C}$. In Fraction 2, the sample pretreated at $15\ \text{°C}$ recovers $100\ \%$ of its maximum activity, whereas the one pretreated at $70\ \text{°C}$ maintains an activity of $0\ \%$.
- a) Interpret molecularly the results of Fraction 2 for the $15\ \text{°C}$ and $70\ \text{°C}$ samples, distinguishing between the kinetic energy of the system and protein denaturation.
- b) Predict how the curve for Fraction 1 would change if an equivalent enzyme purified from the thermophilic bacterium Thermus aquaticus ($T_{\text{optimum}} \approx 75\ \text{°C}$) were used, and justify what adaptations in the bonds of its tertiary structure allow it to be functional at that temperature.
Cofactors, saturation and enzyme inhibition
The apoenzyme together with its functional cofactor forms the holoenzyme.
As the substrate increases with a fixed amount of enzyme, the initial rate rises until it approaches a maximum rate: the active sites become saturated. A competitive inhibitor occupies the active site; its effect can be reduced by increasing the substrate. In pure non-competitive inhibition the maximum rate decreases and adding substrate does not restore it.
Back to the start: the potato (or blood) contains the enzyme catalase, which lowers the activation energy for breaking down hydrogen peroxide, so the oxygen is released at once and the enzyme is not used up.