Biochemistry 2 Flashcards
Proteins
Amino acids are the building blocks for proteins
They are formed from the elements Amino Acid: Carbon, Hydrogen, Oxygen and Nitrogen.
The nitrogen component distinguishes proteins from fats and carbohydrates
amino acids
The body needs 20 different amino acids to create the proteins needed to function.
• Every amino acid has a carboxyl group/acid (-COOH) and an amino group (-NH3).
Each individual amino acid has a side chain (labelled R) that determines its characteristics
Peptides
Amino acids join together using dehydration synthesis (by removing water), to create ‘peptide bonds’
dipeptide
When 2 amino acids are joined together by a peptide bond
tripeptide
When 3 amino acids are joined together by a peptide bond
Glutathione
The powerful antioxidant ‘Glutathione’ is a tripeptide containing the amino acids L-cysteine, L-glutamate and glycine. Cysteine is the amino acid most commonly limiting glutathione production. So by ensuring a good intake of cysteine (from foods such as legumes, sunflower seeds & eggs), you will optimise glutathione production.
Amino Acid Types
Amino acids with acidic side chains can release hydrogen ions; whether they do or not depends on the pH of the surrounding fluid.
- Amino acids with basic side chains can bind to hydrogen ions; whether they do or not depends on the pH of the surrounding fluid.
- This means the pH of the fluid the protein is in will affect its 3D structure and, therefore, its function.
Non-polar and Polar amino acids
Non-polar amino acids are hydrophobic.
When a protein folds up in a watery environment they like to be on the inside of the protein structure, away from any water. These include Tryptophan (used to produce serotonin – which stimulates gut motility and digestive juices).
• Polar amino acids are hydrophilic.
When a protein folds up in a watery environment they like to be on the outside of the protein structure, interacting with the polar water molecules. These include Tyrosine (which is also used to create adrenaline and thyroxine!).
• It is the combinations of the polar and non-polar amino acids that ultimately determine the 3D shape of the protein.
Function of Proteins
- Structure of body tissues, e.g. Collagen.
- Movement e.g. Actin and myosin fibres (in muscles).
- Carrier molecules, e.g. Haemoglobin.
- Storage molecule, e.g. Ferritin (iron).
- Fluid balance in the blood, e.g. Albumin.
- Enzymes (for reactions in the body).
- Hormones, e.g. Insulin.
- Immune function, e.g. Antibodies.
- Clotting mechanisms, e.g. clotting factors.
- Alternative energy source – Much less efficient than carbohydrate or fat so only used during dietary deficiency.
- Cell membrane proteins, e.g. receptors.
Denaturation
If a protein’s 3D structure changes or ‘unfolds’, we say it has ‘denatured’. Denatured proteins no longer function correctly, e.g. protein fibres in muscle cells.
• Proteins can be denatured by:
– Heat, e.g. cooking (i.e. egg whites become denatured during cooking) and pH changes. Note that this is not necessarily bad.
– Heavy metals, e.g. lead and mercury (these can damage proteins such as hormones, antibodies and enzymes). Exposure must be minimised. Natural chelating agents such as Coriander and Chlorella remove heavy metals from the body. Try steeping 2 tsp of Coriander in 1 cup of boiling water, with mint for flavour.
Protein Digestion
To digest proteins, the body uses enzymes to help break the peptide bonds between the amino acids.
- These bonds can be broken in a hydrolysis reaction – using water.
- Proteins are mechanically broken down in the mouth, increasing the surface area for the enzymes to work on.
- However, the chemical digestion of proteins begins in the stomach where the enzyme pepsin breaks down long protein chains.
- Pepsin is released by gastric chief cells in the inactive form ‘pepsinogen’. It is the presence of HCl that converts this into pepsin. Pepsin needs to be at pH 2 in order to function correctly, so adequate stomach acid is critical for good protein digestion.
As protein rich-chyme enters the small intestine, the hormone CCK is released, which triggers the pancreas to release pancreatic juices.
• Pancreatic juices contain proteases called trypsin and chymotrypsin.
In the small intestine, these shorter protein chains, that have entered the small intestine from the stomach, are further broken down into tripeptides, dipeptides and single amino acids by pancreatic proteases and brush border enzymes. because it was first
• Amino acids and small peptides are then absorbed into the blood.
Nucleic Acids
Nucleic acids are the largest molecules in the body and are used to store our genetic information.
• The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
nucleotides
The building blocks of nucleic acids are called ‘nucleotides’.
• Nucleotides consist of a phosphate group, sugar and a nitrogenous base.
Functions of Nucleic Acids
DNA stores genetic information and acts like a recipe book.
- Every living cell contains at least one DNA molecule to carry genetic information from one generation to the next.
- Human DNA molecules are huge. If a DNA molecule could be extracted from a human cell, it would be 2m long.
- DNA acts as a template for protein synthesis (a recipe for producing proteins). RNA is used to copy specific sub-sections of DNA called ‘genes’, and translate it into proteins. There are 20,000-25,000 genes in the human genome (complete set of DNA).
DNA
The nucleotides in DNA contain the 5-carbon sugar ‘deoxyribose’.
• DNA has four possible nucleotide bases (amino acids):
– Adenine (A) - a ‘purine’
– Cytosine (C)
– Guanine (G) - a ‘purine’
– Thymine (T)
• Purine-rich foods (e.g. shellfish, red meats) contain lots of adenine and guanine bases. These are metabolised to form uric acid and, when in excess, can crystallise in joints and cause gout.
Structure of DNA
DNA has two strands that are wound together like a twisted ladder. This is called the ‘double helix’.
- The two strands are held together by hydrogen bonds (review Biochem. I) between the bases (i.e. in the middle of the ladder), whilst the sugar-phosphate bonds (i.e. at the sides of the ladder) form covalent bonds. The hydrogen bonds are much weaker, which is how DNA is able to “unzip” during protein synthesis.
- Adenine always pairs with Thymine. Guanine always pairs with Cytosine. This is important because the sequences of these pairs will ultimately code for the production of a certain protein (i.e. a hormone, such as insulin).
RNA
RNA (Ribonucleic acid) is a single strand of nucleotides which contains the sugar ‘ribose’. Whereas DNA is a double stranded structure and instead has the sugar ‘deoxyribose’.
• A molecule of mRNA (messenger RNA) copies the ‘recipe’ in DNA (a ‘gene’). This is known as transcription. The mRNA then travels to a ribosome where it is ‘read’. The ribosome then produces the protein coded for, e.g. a hormone. This is called translation.
telomeres
The end sections of DNA.
– The length of telomeres shortens as cells and tissues age. It has been shown that this process of ageing can accelerate from causes such as stress, poor nutrition, poor sleep, chemical agents, a lack of exercise and even negative thoughts.
– The herb Centella asiatica (Gotu kola) has been shown to reduce telomere shortening and hence support healthy aging.
Mutation
A mutation is a change in the DNA sequence.
- Since the DNA sequence provides the code for making proteins, a mutation can cause a change in the sequence of amino acids in the protein.
- This is turn can cause the protein to be a slightly different shape. The shape change may affect the functionality of the protein.
MTHFR
‘MTHFR’ is an enzyme necessary for con folate (B9) into a form used for methylation.
- This active form of folate (‘methylfolate’) is involved in the metabolism of the amino acid homocysteine a metabolite associated with heart disease and dementia.
- The mutation causes the enzyme to fold up into an abnormal shape.
- People with MTHFR mutations may have higher homocysteine levels and may benefit from taking methylfolate (already activated).
- Harm can come from excessive fortified folic acid foods, e.g. cereals.
- It is worth noting that methylation is a process also required to remove toxic metals such as mercury from the body.
Enzymes
Enzymes are biological catalysts made from protein.
- They speed up reactions, but are not themselves changed in the process, so they can be used over and over again.
- Enzymes generally end in the suffix –ase.
E.g. lipase digests fats, proteases digest proteins.
- In enzymatic reactions, the molecules at the beginning of the process are called ‘substrates’, and the enzyme converts them into different molecules known as the ‘products’, e.g. pepsin is the enzyme, a protein is the substrate, and shorter protein chains are the products.
- When the substrate binds to the enzyme, the enzyme ‘stresses’ the bond in the substrate, which weakens it and allows your body to more easily break the bond, so that the products can be released.
Many biological reactions are actually very, very slow when performed in a test tube or when at body temperature.
• Enzymes bind temporarily to the substrate, providing an alternative pathway to get to the end result much quicker. As this means a lower activation energy point, it uses less energy.
How Enzymes Work
Each enzyme has a specific region called an active site. This is where the substrate binds. The active site has a unique shape that is complementary to the shape of a substrate molecule.
- This model is often referred to as ‘lock and key’.
- Enzymes are highly specific and require optimum conditions: temperature & pH
Enzyme Cofactors
Some enzymes require co-factors for activity. These are usually minerals or vitamins. Without these, the enzyme is inactive.
• For example:
– Zinc is required for the enzyme ‘alcohol dehydrogenase’, that breaks down alcohol as part of the alcohol detoxification process.
– Selenium is required for the antioxidant enzyme ‘glutathione peroxidase’.
• A lack of cofactor can lead to a reduction in enzyme activity.
This is relevant in clinic, in that deficiencies in these co-factors would effect enzyme reactions all over the body. E.g. a lack of selenium impairs the liver’s ability to produce Glutathione peroxidase.
Enzymes – Substrate Concentration
Substrate concentration can affect the speed of enzyme reaction (e.g. a substrate could be ‘starch’, whilst the enzyme is ‘amylase’).
- An increase in the substrate concentration means that more of the enzyme molecules can be utilised.
- As more enzymes become involved in reactions, the rate of reaction increases.
- Eventually, all the enzymes are being involved in reactions. When this happens, some of the substrate must “wait” for enzymes to clear their active sites before the enzyme can fit with them so the reaction cannot become any faster.
Enzymes: pH
Changes in pH can affect the properties of amino acid side chains.
• In acidic conditions, amino acid side chains can bind to H+.
In basic (alkaline) conditions, the side chains can lose H+.
- These changes can affect whether or not these side chains can form the bonds and interactions which are essential for the 3D structure of the enzyme.
- Enzymes can be denatured by conditions that are too acidic or too basic.
Salivary amylase is in its correct shape when the surrounding pH is about 7. When swallowed, the amylase enters the stomach (a pH of 2-3), and now the amino acids in amylase pick up the protons from stomach acid; this changes the shape of amylase, rendering the enzyme inactive.
- Hence you must chew your food well, because amylase stops working in the stomach.
- Whereas pepsin is the correct shape at a pH of 2.
So if stomach acid production is not sufficient, pepsin will not fold up in the right way in order for it to effectively digest proteins.
Enzymes: Temperature
At high temperatures, molecules move much faster. This leads to more collisions and, therefore, a faster reaction rate.
- However, if the atoms in an enzyme vibrate too much, the weak bonds holding the 3D structure together can break and the enzyme becomes denatured (the structure “unravels”).
- Once the 3D structure is lost, the enzyme no longer works.
- Enzymes usually have an optimum temperature at which they work best. For human enzymes, this is body temperature (~37°C).
- A fever works effectively by speeding up the immune reactions in the body. It is important this does not go beyond 40°C, because then enzymes will denature and metabolic processes will break down.
