Chemistry and Biochemistry II; Proteins, enzymes, genetics and energy production with their clinical applications

Question 1

Learning Outcomes

Answer 1

• The structure and function of proteins
• The structure of genetic material, mutations, as well as the role of nutrition
• The activity and importance of enzymes, including enzymes found in food and their therapeutic applications
• The process of energy production and the key enzymes and nutrient co-factors, as well as mitochondrial damage

Question 2

Proteins

Answer 2

Amino acids are the building blocks of proteins.
* They are formed from the elements carbon, hydrogen, oxygen and nitrogen. The nitrogen component distinguishes proteins from fats and carbohydrates.
* 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
Amino acids = named because of the ‘amino group’ and ‘acid’ group, Carbo = carbon, -Oxy = oxygen)

Question 3

Peptides

Answer 3

Amino acids join together using dehydration synthesis (by removing water) to create ‘peptide bonds’.
* When two amino acids are joined together by peptide bond, it is called a dipeptide. When three joined together, it is a tripeptide.
* Aspartame is an example of a harmful dipeptide. It does not occur in nature and is a neurotoxin. It is manufactured to become an artificial sweetener
* A 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 and eggs) you will optimise glutathione production
Di = two, peptide = protein

Question 4

Amino acids types - side chains

Answer 4

• 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 it will affect its 3-D structure and, therefore, its function
• Look at what happens in ceviche –when you squeeze lemon juice (citric acid) on raw fish, the protein changes structure as it is denatured. It changes from soft and translucent to firm and more opaque. Ceviche does not necessarily kill potentially harmful organisms, including parasites.

Question 5

Amino acid types; non-polar and polar

Answer 5

• Non-polar amino acids are hydrophobic. When 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 of 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 3-D shape of the protein
  Hydro = water, Phillic = loving, phobic = hating

Question 6

Functions of proteins

Answer 6

• Structure of body tissues, e.g. collagen
• Movement e.g. actin and myosin fibres (in muscles)
• Carrier molecules, e.g. haemoglobin
• Storage molecules, 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

Question 7

Denaturation

Answer 7

The 3-D structure of the protein is key to its function. Proteins work like a ‘lock and key’. If a protein 3-D structure changes or ‘unfolds’, we say it has ‘denatured’. Denatured proteins no longer functioning correctly, e.g. protein fibres in muscle cells.
* Proteins can be denatured by:
o Heat, e.g. cooking (i.e. egg whites become denatured during cooking) and pH changes. (N/B this is not necessarily bad)
o 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, + mint for flavour)
De = reversal, naturation = nature

Question 8

Protein digestion

Answer 8

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 of 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 convert 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

Question 9

Protein digestion and absorption part 2

Answer 9

• As protein-rich chyme enters the small intestine, the hormone CKK 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
• Amino acid and small peptides are then absorbed into the blood
  Trypsi = Greek for ‘friction’, because it was first obtained by rubbing down the pancreas with Glycerine

Question 10

Nucleic acids

Answer 10

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)
* The building blocks of nucleic acids are called ‘nucleotides’
* Nucleotides consist of a phosphate group, sugar and a nitrogenous base.
Deoxyribose = sugar with 1 oxygen missing, nucleic = ‘nucleus’ / core Functions of nucleic acids

Question 11

Functions of nucleic acids

Answer 11

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 2 m 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 in human genome (complete set of DNA)

Question 12

DNA

Answer 12

The nucleotides in DNA contain the 5-carbon sugar ‘deoxyribose’.
* DNA has four possible nucleotide bases (amino acids):
o Adenine (A) – a ‘purine’
o Cytosine (C)
o Guanine (G) – a ‘purine’
o Thymine (T)
* Purine rich foods (e.g. shellfish, Red meats) contain lots of adenine and guanine bases. These are metabolized to form uric acid and, when in excess, can crystallise and joints and cause gout

Question 13

Structure of DNA

Answer 13

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 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 hormones such as insulin)

Question 14

RNA

Answer 14

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 of the ‘recipe’ in DNA (a ‘gene’). This is known as transcription. The mRNA then travels to ribosomal where it is ‘read’. The ribosome then produces the protein coded for, e.g. a hormone. This is called translation.

Question 15

Genetics

Answer 15

DNA is also used as a manual for making all the proteins in the body, everything from muscle tissue to enzymes
* DNA is condensed to form ‘chromosomes’. The N sections of DNA called ‘telomeres’.
o 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.
o The herb Centella asiatica (Gotu kola) has been shown to reduce telomere shortening and hence support healthy ageing

Question 16

Mutations

Answer 16

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 in turn can cause the protein to be a slightly different shape. The shake change may affect the functionality of the protein
* For example, sickle-cell anaemia involves a mutation of the gene that codes for the production of haemoglobin proteins. When this mutation occurs, the proteins in haemoglobin become abnormally shaped and hence the red blood cells are defective
A ‘mutation’ describes an abnormal change to the genetic sequence. It can be something someone is born with, most commonly occurs during a persons lifespan
* Haemophilia is a disease linked to mutations of the genes associated with the production of clotting factor 8 (haemophilia A) all clotting factor 9 (haemophilia B). As a result, these individuals cannot adequately synthesise key clotting factors and will have problems clotting and stopping bleeding.
* In cancer, mutations occur due to factors such as radiation, poor nutrition, chronic inflammation, medications, chronic stress and carcinogenic chemicals. These mutations that the genes that code for proteins involved in regulating cell division

Question 17

Gene expression

Answer 17

We can’t change our genes but there are many different things that can change our gene expression – which is whether we copy the gene and make the protein or not
* For example, the liver makes many different enzymes involved in breaking down toxins. The more toxins we are exposed to, the more of the enzymes involved in metabolizing that particular toxin the liver will make. This will change the livers ability to metabolise the toxin but may also affect how quickly the liver breaks down other substances that also require this enzyme such as herbs of drugs
* Therefore, the more these enzymes are used, the less the other functions of those enzymes can be fulfilled

Question 18

Gene expression: nutrients

Answer 18

The expression of genes can also be influenced by certain nutrients.
* Metabolites of vitamin A, vitamin D, essential fatty acids and zinc can influence whether a gene is copied on not
* Components of fibre can also have an effect on gene expression by affecting hormone levels and through the metabolites created when intestinal flora feed on the fibre
* It is essential to consider the environment we bath our genes in. Recall that cancerous cells live in an environment that is acidic, anaerobic and glucose– rich. This environment would promote ‘pathological’ gene expression, encouraging excessive cell growth. We must all consider the importance of a lack of oxygen, chronic stress, radiation, vaccine and drug toxins, junk food etc.

Question 19

Gene expression: gene uniqueness

Answer 19

An understanding of genetic uniqueness is essential. Consider
* Why might an individual who is eating rich appliance beta-carotene (a vitamin A precursor) – rich foods be low in vitamin A?
* Why might an individual getting good sunlight exposure and eating vitamin D rich foods be lacking or have low blood vitamin D levels?
* What role can genetics play?

Question 20

Mutations: folate

Answer 20

Gene mutations can affect enzyme activity.
* ‘MTHFR’ is an enzyme necessary for converting 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 the process also required to remove toxic metals such as mercury from the body
Methylation = the process of adding a methyl group (-CH3)

Question 21

Enzymes; as catalysts

Answer 21

Enzymes are biological catalysts made from protein
* They speed up reactions, but are not themselves is changed in the process, so they can be used over and over again
* Enzymes generally and in the suffix –ase. E.g. lipase pays digests fats, proteases digests 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 bonds, so that the products can be released
Catalysts = speed up chemical reactions

Question 22

Enzymes; conditions

Answer 22

Enzymes are vital for life. They participate in every chemical reaction in the body.
* 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
* This allows biological reactions to occur in relative ‘mild conditions’ within the body.

Question 23

Enzymes: how they work

Answer 23

Enzymes are proteins and so fold into very specific 3-D shapes. This is very important for enzymes because the shape is the key to how they 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 complimentary to the shape of a substrate molecule.
* The model is often referred to as ‘lock and key’.
* Enzymes are highly specific and require optimum conditions; temperature and pH

Question 24

Enzymes: the sofa analogy

Answer 24

Imagine shoppers on the high street are your starting materials.
* At 4 AM on a Monday morning they are not very close together and then not moving very fast, so the chance of them meeting and reacting with one another is very small. This is like most of the reactions that occur in the body
* Now imagine the situation on Christmas eve; Shoppers all moving at high speed & close together -it’s easy to see that ‘reactions’ will occur
* This is what happens if we apply heat or pressure to reaction. But we can’t do this in the body…
* Let’s imagine we at least comfortable sofa into the mix
* At 4 AM on a Monday morning, if there was a really comfortable sofa on the high street, the chances are you’d sit down for a little rest. And so would someone else
* When you sit down together it’s much easier for you to meet and react
* This is how enzymes work
* They create a lower energy way for starting materials to meet and react, which allows reactions to happen in the mild conditions within the body

Question 25

Enzyme co-factors

Answer 25

Some enzymes require co-factors for activity. These are usually minerals or vitamins. Without these, the enzyme is inactive.For example:
o Zinc is required for the enzyme ‘alcohol dehydrogenase’, that breaks down alcohol as part of the alcoholic detoxification process
o Selenium is required for the antioxidant enzyme ‘glutathione peroxidase’.
* A lack of co-factor can lead to a reduction in enzyme activity. This is relevant in clinic, in that deficiencies in these co-factors would affect enzyme reactions all over the body, e.g. a lack of selenium impairs the livers ability to produce glutathione peroxidase
De = removal, hydrogen = hydrogen, -ase = enzyme

Question 26

Enzymes: substrate concentration

Answer 26

Substate 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 utilized
* As more enzymes are involved in reaction - 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
A key example to contextualise the importance of substrate concentration in nutrition:
* If someone ingests lots of omega-6s and a small amount of omega-3s, because these are converted using the same enzymes, the omega-6 will occupy the enzymes’ active sites
* Therefore, the less abundant omega-3 will not be converted
* Hence, it is vital to have a good balance of omega-3 and -6

Question 27

Enzymes: pH and amino acid side chains

Answer 27

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 & interactions which are essential for 3-D structure of enzyme
* Enzymes can be denatured by conditions that are too acidic or too basic
* This is why the body works so hard to control pH

Question 28

Enzymes: pH examples

Answer 28

Enzymes have an optimal pH at which they function best. This is the pH where the protein is the correct shape. For human enzymes the pH range of optimal function is often very narrow
* Salivary amylase is in its correct shape when the surrounding pH is about 7. When swallowed, the amylase enters the stomach (pH of 2 -3), and now the amino acids in amylase pick up the protons from stomach acid; this changes the shape of a amylase, rendering the enzyme inactive
* Hence you chew your food well because amylase stops working in the stomach
* Whereas pepsin is the correct shape at 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

Question 29

Enzymes: Temperature

Answer 29

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 3-D structure together can break and the enzymes become denatured (the structure ‘unravels’)
* Once the 3-D 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

Question 30

Digestive enzymes

Answer 30

The gastrointestinal tract (GIT) contain key digestive enzymes:
* Saliva: Salivary amylase
* Stomach: Gastric lipase, pepsinogen – pepsin
* Pancreas: pancreatic amylase, pancreatic lipase, pancreatic proteases
* Villi (brush border): sucrase, maltase, lactase

Question 31

Digestive enzymes: Diet, stress and nutritional deficiencies

Answer 31

Modern dietary habits mean that many people often struggle to produce enough digestive enzymes
* Enzymes that go into the digestive system are lost once they have done their job by acting on food substrates and need to be replaced
* Constantly eating taxes enzyme production. By eating more often, more enzymes are produced and used up, so that eventually, enzyme production cannot meet the demand. As a result, overeating can impair the digestions and hence absorption of nutrients in food.
* Furthermore, it is important to avoid drinking whilst eating, as this dilutes the digestive juices containing enzymes.
* As well as overheating, digestive enzyme output can also be low due to factors such As prolonged stress and nutritional deficiencies

Question 32

Digestive enzymes: herbal bitters

Answer 32

• Herbal bitters can be used to stimulate the production of digestive enzymes. They should be taken 15–20 minutes before meals. Bitters are thought to work by stimulating the Vagus nerve and also trigger the release of cholecystokinin (CCK)
• These include gentian (in Swedish bitters), barberry bark, andographis and dandelion. Also include bitter greens.

Question 33

Enzymes in food

Answer 33

Plants, like humans, also contain enzymes
* Some of these have similar functions to human enzymes – for example the bromelain in pineapples and the papain in papayas are both proteases– enzymes that help digests proteins
* Unlike human enzymes, plant enzymes tolerate a wider range of pH. It has been demonstrated that bromelain remains intact as it passes through the low pH of the stomach. If the digestive tract is otherwise healthy, the rate of absorption can be very high.
* They are less likely to be denatured by the changing pH conditions through the digestive system
* However, they are denatured by heat. Furthermore, enzymes will be destroyed by microwaving food
Other foods that contain an abundance of enzymes:
* Sprouts: contain up to 100 times more enzymes than fruit & vegetables
* Kiwi: contains the proteolytic enzyme ‘actinidin’. This is the predominant enzyme in kiwi fruit and aids protein digestive
* Avocado: contains the enzyme lipase, which helps digests the fats in avocado
* Garlic: contains the sulphur rich phytonutrient ‘alliin’ and the enzyme which digests it, called ‘allinase’. When a garlic clove is chopped or crushed, the usually separated compounds mix and the enzyme activity converts alliin into ‘allicin’
* Allicin has antimicrobial, antioxidants, cardio – protective and anti-cancer properties

Question 34

Enzymes in food: cooking

Answer 34

Cooking can be damaging to enzyme naturally present in food. The longer the exposure and the higher the heat, the greater the loss
* Enzymes start to be destroyed when food is heated above 40°C. This emphasizes the potential benefit of eating raw foods. Most people consider the upper raw food limit to be 46–40 8°C as there are still some active enzymes after cooking at this temperature.
* The enzymes that remain undamaged in these foods can support digestion, assisting with the breakdown of macronutrients and reducing the digestive burden

Question 35

Raw foods

Answer 35

Raw foods contain more micronutrients then cooked food, i.e. vitamins, minerals, probiotics, antioxidants, reduce free radicals and the need for digestive enzymes
* Cooking often decreases the antioxidant value of food
* Water-soluble compounds can be lost with boiling, e.g. vitamin C which leaches into water
However, some compounds in plant based foods such as lycopene and beta-carotene become more available when heated, as they are released from plant cell walls.
* It may not be advisable for some individuals to eat raw. In some digestive disorders such as small intestinal bacterial overgrowth (SIBO), eating raw can cause immediate bloating
* Brassica (goitrogenic) foods (e.g. turnips, cabbage, radishes) disrupt the uptake of iodine in the thyroid gland. However, goitrogenics are inactivated by the cooking process, so may or may not need to be cooked depending on the thyroid disorder
* As covered earlier, ‘Yin conditions’ may be caused by excessive raw foods. This can cause lethargy, anaemia, a feeling of being cold, through lack of ‘warming Foods’
Goitrogens = substances that disrupt the production of thyroid hormones

Question 36

Enzymes: inflammation

Answer 36

Cyclooxygenase-1 and -2 (COX) and Lipoxygenase-5 (LOX) are enzymes involved in the creation of key inflammatory mediators called prostaglandins and leukotrienes
* Boswellia, curcumin and ginger help to reduce inflammation by inhibiting these enzymes
Lipo = fats, oxygenase = enzymes that oxidises

Question 37

Turmeric, Ginger and Boswell and Boswellia

Answer 37

Boswellia, curcumin and ginger help to reduce inflammation by inhibiting enzymes Cyclooxygenase-1 and -2 (COX) and Lipoxygenase-5 (LOX)
Therapeutic uses:
* Turmeric: easily incorporated into meals. This should be used with black pepper, which significantly enhances absorption of the compound ‘curcumin’. Turmeric is also fat-soluble, so it’s absorption is further supported by the presence of fats, e.g. coconut oil
* Ginger: for maximum medicinal effect use in powder form. Try mixing ¼ tsp to some water. Alternatively grate into boiling water and drink once is steeped in 10 minutes. Also add to meals
* Boswellia: also effective as a powder. Alternatively supplement with pure Boswellia or use frankincense topically

Question 38

Enzyme inhibitors as drugs

Answer 38

Enzyme inhibitors are quite often used as drugs, to decrease the rate of biological reactions. E.g.
* Antibiotics (such as penicillin) work by inactivating an enzyme necessary for the connections of amino acids in bacterial cell walls (both pathogenic and healthy bacteria) which is important for their structure
* Statins work by inhibiting HMG-CoA reductase – the enzyme the liver uses to make cholesterol and CoQ10. This explains why statins also deplete Coq10

Question 39

Enzyme therapies

Answer 39

Systemic enzyme therapy involves taking a large dose of proteolytic enzymes on an empty stomach so that some of the enzymes are able to reach the bloodstream interact

• The proteases are thought to reduce inflammatory processes and aid in the more efficient clearance of damaged tissue
• Commonly used enzymes include bromelain (found in pineapple), serrapeptase and pancreatic enzymes
• The proteolytic enzyme ‘bromelain’ has been shown to have:
  o Anti-inflammatory effects (reduces inflammatory mediators such as ‘bradykinin’) and anti-cancer properties
  o Anti-clotting (acts on fibrinogen); may also have positive effects on atherosclerotic plaques
• biofilms

Question 40

Enzyme therapies: serrapeptase

Answer 40

Serrapeptase is a proteolytic enzyme that has potent anti-inflammatory effects on body tissues.
* This was first isolated from enterobacterium serratia. This microorganism was originally isolated in the late 1960s from the silkworm. Hence the name serrapeptase. It is produced by purification, mainly from the fermentation of serratia
* It is thought to reduce inflammation by:
o Thinning the fluids formed from injury; facilitating fluid drainage.
o Inhibiting the release of pain-mediating chemicals
o Enhances cardiovascular health by breaking down the protein by-product of blood coagulation called ‘fibrin’. It can, therefore, help dissolve blood clots and atherosclerotic plaques

• Serrapeptase reduces pain and swelling without inhibiting prostaglandins and has no gastrointestinal adverse affects (like NSAIDs)
• Serrapeptase alleviates pain by inhibiting the release of bradykinin from inflamed tissues. Serrapeptase hydrolysis bradykinin and histamine, thereby reducing swelling, improving microcirculation, aiding healing, as well as the breakdown of sputum
• Therapeutic uses: inflammatory mediated pain (arthritis, spinal disc injuries), scar tissue, fibrocystic breast disease, endometriosis, autoimmunity, excess mucus, resistant bacterial infections (digests biofilm)
  Brady = slow, kinin = to move (vasodilates)

Question 41

Energy production: nutrition

Answer 41

As nutritional therapists, it is vital to understand that the body does not just need carbohydrates, fats or proteins to create energy.
* There are essential nutrients that support the key processes of energy production. These must also be present in an individual’s diet to ensure that energy (ATP) production is able to operate effectively
* You’ll need to support your clients biochemical processes of energy production.

Question 42

ATP: Adenosine Triphosphate

Answer 42

ATP is the energy currency of the body – the body has to synthesise it before it can spend it
* ATP is used to capture the energy released by reactions in the body such as ‘burning glucose’. ATP is how the body ‘traps’ energy from these reactions in a way that the body can use it
* ATP is a nucleotide with three phosphate groups. This is important because the bonds between phosphate groups contain lots of energy
* When water is added to ATP, one phosphate group is removed, releasing energy via a hydrolysis reaction. For example, so we can move
Adenosine = adrenaline combined with ribose, tri – three

Question 43

ATP and magnesium

Answer 43

ATP is always present as a magnesium– ATP complex
* Magnesium binds to phosphate groups in ATP, holding the molecule in a slightly curved / strained shape that aids the loss of phosphate, facilitating energy release
* Without magnesium, ATP isn’t biologically active as it is difficult to release the energy from between the phosphate groups
* Hence low-energy is a symptom of magnesium insufficiency
* Magnesium is a central component of chlorophyll (like how iron is at the core haemoglobin) = increased intake of green vegetables

Question 44

Functions of ATP

Answer 44

ATP is needed to:
* Capture the energy from oxidisation reactions what (i.e. the energy created when we burnt fuel like glucose)
* Drive body reactions (DG building proteins)
* Fuel movement
* Transport substances across membranes (active transport)
* Cell division

Question 45

Turning food into energy

Answer 45

The process of turning glucose, fat or even proteins into energy isn’t straightforward
* The energy isn’t always released in handy ATP sized packages
* So at certain points during the process, the body has to use ‘Energy carriers’ to temporarily capture the energy released
* And then we can convert the trapped energy into ATP molecules later
* The main intermediate energy carriers are derived from B vitamins

Question 46

Energy carriers

Answer 46

1. NAD: NAD is made from vitamin B3 (niacin), or from the amino acids tryptopan and aspartic acid. When it traps energy, NAD becomes NADH
2. FAD: FAD is made from vitamin B2 (riboflavin). When it traps energy, FAD becomes FADH2
   * NAD or FAD sweep in and steal electrons and a hydrogen from the glucose (or fats)
   * They trap the energy temporarily
   * Hence, an adequate intake of B vitamins is essential for optimal energy levels

Question 47

Energy from carbohydrates; cellular respiration:

Answer 47

Carbohydrates are broken down into glucose by the digestive process.
* Glucose can then be oxidised (chemically ‘burned’ inside the body), to form ATP
* This process is known as cellular respiration and involves four steps:
1. Glycolysis (or anaerobic cellular respiration) – in the cytosol
2. Formation of acetyl CoA }
3. Krebs cycle } – occur in the mitochondria
4. Electron transport chain }
Glyco = sugar, lysis = splitting

Question 48

Cellular respiration: 1; Glycolysis

Answer 48

Glycolysis is the first stage of aerobic and anaerobic respiration and occurs in the cytosol.
* Through the 10 steps in glycolysis, glucose is transformed into two molecules of a substance called pyruvate. Through this ‘splitting’ of glucose, some energy is released, but 2 ATP is used up
* Glucose contains 6 carbon atoms, whilst pyruvate contains 3 (so goes from 6-carbon structure to 2×3-carbon structures)
* Energy is directly released and trapped as 4 ATP and 2 NADH. There is therefore, a net gain of 2 ATP and the 2 NADH (trapped energy)
* Glycolysis therefore, requires magnesium B3
Glyco = sugar (glucose), lysis = splitting, cytosol = cell liquid, pyruvate = a 3-carbon structure. It is key in cell respiration

Question 49

Cellular respiration: Anaerobic respiration

Answer 49

Glycolysis can occur with or without oxygen
* When oxygen is available, NADH can be recycled in the electron transport chain and turned into a ATP. But when oxygen isn’t available, NADH cannot be recycled
* In order to allow energy production to continue, NADH reacts with pyruvate (to keep glycolysis going), turning it into lactic acid (this can cause muscle pain and also challenges the pH balance).
* Anaerobic respiration would ideally only be used for short bursts of activity, but many individuals are chronically ‘hypoxic’ due to factors such as pollution, stress (poor breathing mechanics), a lack of exercise, smoking and obesity. The anaerobic body accumulates lactic acid and creates an acidic environment

Question 50

Cellular respiration: Energy production: oxygen

Answer 50

The presence of oxygen is essential for the body to create an aerobic, alkaline and energy-abundant body
* Given that so many clients present in a relative state of ‘hypoxia’, we must be effective at oxygenating their bodies
* Try the following strategies:
o Exercise regularly (3–5 X a week). Include outdoor exercise
o Diaphragm breathing exercises
o Get outdoors in nature (plants produce oxygen)
o Optimise dietary iron intake to support oxygen delivery to tissues around the body. Consider a green smoothie
o Improve clientS’ desk posture (if they sit at work) and encourage more movement

Question 51

Cellular respiration: 2; Acetyl CoA formation

Answer 51

If oxygen is plentiful, pyruvate will enter the mitochondria and be converted to ‘Acetyl CoA’, ready to enter the Krebs cycle. This process allows us to get more energy out of glucose.
* Pyruvate will react with vitamin B5 carrier molecule, which then allows it to enter the mitochondria
* This process requires vitamin B1, lipoic acid and vitamin B5. Vitamin B1 and lipoic acid enable the pyruvate to lose one of its 3 carbon atoms. Acetyl CoA hence has 2 carbons
* During the transformation, 2 more packets of energy are trapped as NADH

Question 52

Cellular respiration: Coenzyme A

Answer 52

Coenzyme A is naturally synthesised from pantothenate (Vitamin B5), which is found in foods such as meat, vegetables, cereal grains, legumes and eggs.
* It is a vital carrier molecule to transport the acetyl group into the mitochondria so that it can participate in the Kreb cycle
* Coenzyme A carries energy in a high-energy bond
* One glucose produces 2 pyruvate and hence 2 acetyl CoA

Question 53

Cellular respiration: 3; The Krebs cycle

Answer 53

The Krebs cycle is simply a series of reactions, where Acetyl CoA is modified by enzymes. Through this process, energy is released or trapped.

• The Krebs cycle is also known as the citric acid cycle (refers to the first molecule that forms during the cycle’s reaction – citrate)
• Occurs in the mitochondrial matrix
• Acetyl CoA enters the Krebs cycle. For each glucose, enough energy is released to make:
  o 2 ATP
  o 6 NADH
  o 2 FADH
• The Krebs cycle requires the following nutrients – magnesium, manganese, iron, B1, B2, B3
• Many of the enzymes can be easily blocked by heavy metals just aluminium and mercury

Question 54

Cellular respiration: 4; The Electron Transport Chain

Answer 54

The final step in the process allows the energy trapped in the NADH and FADH2 to be turned into a ATP with the help of four enzyme complexes which are embedded in the inner folds of the mitochondria
* Oxygen is very much essential for this step to occur. You should consider how well your client is oxygenating their body. A hypoxic environment will reduce their ability to produce ATP.
* Without oxygen, NAD and FAD cannot be recycled

Question 55

Cellular respiration: enzyme complexes Co-factors

Answer 55

Each of the four enzyme complexes in the electron transport chain requires certain nutrients as cofactors:

1. Complex I: required iron and sulphur
2. Complex II: requires CoQ10
3. Complex III: requires iron
4. Complex IV: requires copper ions

Question 56

Cellular respiration: Summary

Answer 56

One glucose molecule can go through the following four stages to yield a total of 38 ATP molecules:
1. Glycolysis
2. Acetyl CoA formation
3. Krebs cycle
4. Electron Transport Chain

Question 57

CoQ10

Answer 57

Coenzyme Q 10 is a key component of the electron transport chain and is stored in the mitochondria.
* CoQ10 levels are depleted by statin use, which act on the pathway shared for cholesterol and CoQ10 synthesis. This explains adverse effects such as muscle aching and fatigue
* CoQ10 has antioxidant properties and helps to recycle other antioxidants such as vitamins C and E. It therefore, reduces free radical damage, which is a common cause of mitochondrial damage. In addition CoQ10 slows down ageing and also inhibits arterial LDL oxidation.
* Sources: meat, poultry, fish (especially sardines and anchovies). Nuts, sesame seeds, broccoli, cauliflower, oranges, strawberries

Question 58

Mitochondrial damage

Answer 58

Mitochondrial damage can occur due to:
- Free radicals
- Medical drugs and alcohol; these increase free radicals, decrease antioxidants (i.e. glutathione) and deplete key nutrients
- Environmental toxins: pollution, heavy metals, BPA (in plastic)

• This damage may compromise the electron transport chain without generating energy
• Poor mitochondrial functioning is linked to:
• Fibromyalgia, type II diabetes, chronic fatigue syndrome, the pathogenesis

Question 59

Supporting mitochondria

Answer 59

To support mitochondrial health:
* Reduce toxic load (i.e. heavy metals, free radicals, chemicals injected / inhaled /injected to / absorbed through the skin etc)
* Increase nutrient cofactors
* Increased production of glutathione and glutathione peroxidase (by increasing sulphur and selenium rich foods) and mitochondria antioxidants including Coq10
* Support detoxification (liver) and elimination (bowel, kidneys, skin, lungs) processes
* Herbal medicines can also be used to support mitochondrial function in the following ways:
o Supporting mitochondrial functions. These include adaptogenic herbs (especially ginseng, astragalus, rhodiola), as well ginkgo biloba, Rosemary and curcumim (turmeric).
o ‘cleansing the blood’ and removing encumbering elements. These include burdock and dandelion
Adaptogen = helps the body adapt to stress

Question 60

Energy from carbohydrates

Answer 60

Overall, one molecule of glucose makes 38 molecules of ATP during aerobic respiration (occurs in the presence of oxygen)
* This is far more efficient than anaerobic respiration which only makes two ATP
* Water is formed when the electrons combine with oxygen

Question 61

Energy from fats

Answer 61

In the absence of sufficient carbohydrates, fats can also be used for energy production
* Lipases split triglycerides from adipose tissue into fatty acids and glycerol
* The fatty acids are transported to the liver, where the body uses a process called beta–oxidation to convert them into molecules of a acetyl CoA is
* The acetyl CoA can then enter the Krebs cycle, just like carbohydrates
* Fat yields a lot more energy than carbohydrates. So whilst burning carbohydrate is easier, burning fats is more efficient

Question 62

Getting into the mitochondria

Answer 62

In order to get into the mitochondria and be used for energy, fatty acids must first combine with co– enzyme A (from vitamin B5)
* This process occurs ATP, and therefore magnesium
* A carnitine– dependent enzyme is then needed to ferry the fatty acid into the mitochondria
* L–carnitine is therefore required to transport fatty acid into the mitochondria. This explains why L-carnitine is often found in weight loss formulas, to help the fatty acids enter the mitochondria and be ‘burned’ for energy

Question 63

Beta-oxidation

Answer 63

• The aim of beta-oxidation is to gradually chop the fatty acids chain into acetyl CoAs, ready to go into the Krebs cycle. This process occurs in the mitochondria.
• Beta-oxidation requires Vitamin B2, Vitamin B3 and sulphur. This produces energy
• The process repeats until the entire fatty acids chain is broken down into acetyl CoA units, which can then enter the Krebs Cycle. The amount of energy produced depends on the length of the fatty acid chain.
  Beta – oxidation = beta carbon in the fatty acid chains is oxidised

Question 64

Ketone bodies

Answer 64

Most body tissues can use fatty acids for energy directly when carbohydrates are in short supply, but the brain cannot!
* The brain gets its energy from ketone bodies when sufficient glucose is not available, e.g. fasting
* The mitochondria of liver cells can convert acetyl-CoA into ketone bodies – acetone, acetoacetic acid and B-hydroxybutyrate
* These can cross the blood brain barrier & be used as a source of energy
* Ketone bodies can also be formed when protein is used energy

Question 65

Ketosis and ketoacidosis

Answer 65

The production of ketones is called ‘ketogenesis’. The body state of forming ketones is known as ‘ketosis’.
* Ketosis can occur during high-fat (and low carbohydrate) diet and whilst fasting. This state is highly beneficial to the body
* Ketosis is never harmful from diet alone. Although, in some pathological states, ketone bodies form in excessively high quantities; this creates a state known as ‘ketoacidosis’. This dangerous state can occur in diabetes mellitus and alcoholism.
* Both acetoacetic acid and beta-hydroxybutyrate our acidic, so if levels of these ketone bodies are extremely high, the pH of the blood drops. This is dangerous in that it affects the blood pH.
* Ketoacidosis can be smelled on a person’s breath. This is due to acetone (smells like nail varnish remover)

Question 66

Ketosis

Answer 66

Being in Ketosis has been shown to be of benefit in certain disease states:
* A ketogenic diet is sometimes recommended to children with her refractory epilepsy, to help control seizures. It increases the amount of the inhibitory neurotransmitter GABA in the brain.
* Ketosis has also been shown to enhance mitochondrial function and seems to be of huge benefit in neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
* Normal cells can readily adapt to using ketones, but cancerous cells cannot because they rely solely on glucose for their metabolism

Question 67

Fasting

Answer 67

Fasting describes abstinence from food for a specific period of time.
* Fasting prevents the body from expending excessive amount of energy digesting food. Instead, it allows the body to focus its energy on other functions such as healing and regenerating.
* Fasting encourages the body to enter a state of ketosis. This is important, because fats also yield more energy than carbohydrates. This can be an effective way of increasing energy levels.
* The key types of fasting include:
o Intermittent fasting
o Vegetable juice fasting
o Juice fasting
o Water fasting

Question 68

Energy from protein

Answer 68

The carbon parts of amino acids can be broken down to generate ATP, or they can be used for gluconeogenesis – making glucose
* One key points in the degradation of all amino acids is the lots of nitrogen. Vitamins B3 and B6 are important co-factors – both of which help remove nitrogen
* For Amino acids to enter the Krebs cycle, or to be used to make other molecules, they must first lose their amine (NH2) group
* This results in the creation of the ammonia (NH3). Most ammonia is converted to urea in the ‘urea cycle’.

Question 69

Gluconeogenesis

Answer 69

Gluconeogenesis describes the formation of new glucose from other non-carbohydrate sources. Key examples include:
o Pyruvate
o Lactic acid (the heart does this)
o Glycerol
o Some amino acids (e.g. glutamine)
* Takes place in the liver and, to a lesser extent, the kidneys during periods of fasting, starvation or intense exercise. The process requires energy (ATP)
* Biotin is an important co-factor for gluconeogenesis
Gluco = glucose, neo = new, Genesis = formation

Question 70

Energy from food

Answer 70

Adults in their fed state will obtain their energy is:
* 47% from carbohydrate
* 38% fat
* 15% protein

• In fasting states, the body will source its energy from glycogen, then fat, then available protein
• The major source of energy for the body are:
  o Glucose; from carbohydrates
  o Fatty acids; from fat metabolism
  o Ketone bodies; from fat or amino acid metabolism
  o Amino acids; from protein (or body if starving)

Question 71

Energy and Naturopathy

Answer 71

It is also important to consider naturopathic principles when it comes to energy production.
* Given that all body processes are driven by the Vital Force (or Qi/Prana), an illness or pathology can be described as a blockage or insufficiency of the Vital Force
* As naturopathic practitioners, we must try to establish why the Vital Force is obstructed, e.g. stress, toxins/chemicals, a lack of balance life
* Nutrition, herbs, homoeopathy and acupuncture can support the flow of Vital Force