BIOCHEMICAL CONNECTIONS II
ENZYMES AS MARKERS OF DISEASES
- Are the basic elememt that activate all functions in the body.
- 3 classes:
- Metabolic enzyme-runs our body
- Digestive enzyme-for digestion of food
- Food enzyme-present in raw foods
- AST (Serum Glutamic-Oxalocetic Transaminase - SGOT)
Normal Adult Range: 0 - 42 U/L
- LDH (Lactic Acid Dehydrogenase)
Normal Adult Range: 0 - 250 U/L
- ALT (Serum Glutamic-Pyruvic Transaminase - SGPT)
Normal Adult Range: 0 - 48 U/L
- When ALT is generally higher than AST=LIVER DAMAGE
- When AST is generally higher than AST=LIVER CIRRHOSIS
- Less than 4x the Normal level=CHRONIC HEPATITIS
- Very high level(more than 10x the Normal level)=ACUTE PANCREATITIS
Alkaline Phosphatase (ALP)
»Normal Adult Range: 20 - 125 U/L
»Normal Childrens Range: 40 - 400 U/L
Gamma-Glutamyl Transpeptidase (GGT)
» Normal Adult Female Range: 0 - 45 U/L
»Normal Adult Male Range: 0 - 65 U/L
- Creatine Phosphokinase (CK)
- CK-MB CK Isoenzyme
- < 12 IU/L if total CK is <400 IU/L
- <3.5% of total CK if total CK is >400 IU/L
- Lactate dehydrogenase (LDH)
5 types of LDH and their Normal Distribution & Levels in Nondisease/injury:
- LDH 3 - Found in a variety of organs and is 18% - 25% of LDH 1 - Found in heart and red-blood cells and is 17% - 27% of the normal serum total.
- LDH 2 - Found in heart and red-blood cells and is 27% - 37% of the normal serum total.
- LDH 4 - Found in a variety of organs and is 3% - 8% of the normal serum total.
- LDH 5 - Found in liver and skeletal muscle and is 0% - 5% of the normal serum total.
Following a myocardial infarct the serum levels of LDH rise within 24-48 hours reaching a peak by 2-3 days and return to normal in 5-10 days.
Especially diagnostic is a comparison of the LDH-1/LDH-2 ratio. Normally, this ratio is less than 1.
A reversal of this ration is referred to as a "flipped LDH." Following an acute myocardial infarc the flipped LDH ratio will appear in 12-24 hours and is definitely present by 48 hours in over 80% of patients.
Also important is the fact that persons suffering chest pain due to angina only will not likely have altered LDH levels.
Markers of Cholestasis:
- Alkaline Phosphatase (AP)
(Normal values 85-240 U/L)
- Gamma Glutamyl Transpeptidase (GGT)
(Normal values 5-40 U/L)
GGT can be induced by alcohol intake (particularly sensitive) and some drugs (phenytoin, barbiturates).
ARTERIOSCLEROSIS & CORONARY HEART DISEASE
- The term arteriosclerosis is often misused by the layperson
- correct full name is 'arteriosclerosis obliterans’
- formation of plaques of cholesterol, platelets,fibrin, and other substances on the arterial walls
- leads to progressive degrees of blockage of thearterial circulation.
- smoking, high cholesterol levels (diet), high blood pressure as well as hereditary susceptibility and diabetes
- within the arterial walls
- Hereditary factors
- Being male
- Cigarette smoking and high blood pressure
- High blood cholesterol levels
- Risk increases with age
- the most common site is the arteries of the legs
- is unusual for other areas to be affected without the legs being involved, but those with arteriosclerosis in the leg, have a much higher incidence of heart disease, stroke, and kidney artery blockage.
- Where coronary arteries are affected, this will cause angina (chest pain) or even heart attack. If the arteries in the brain are affected, this can lead to a stroke
Treatment & Drug Therapy:
- ranges from light exercise and drug therapy to surgery
- oldest and most common agents are the nitrates, derivatives of nitroglycerine (to dilate the C. arteries and improve blood supply to the heart)
- "beta blockers"- to decrease heart rate and lower Oxygen use by the heart
- calcium channel blockers -to relax the C arteries and all systemic arteries and thus reduce the workload for the heart
- Coronary Heart Disease/coronary artery disease
- narrowing of the small blood vessels that supply blood and oxygen to the heart
- results from the build up offatty material and plaque
- leading cause of death in developing countries
- Family history of coronary heart disease
- Male gender
- Age (65 and greater)
- Tobacco smoking
- High blood pressure
- High cholesterol levels
- Lack of physical activity or exercise
- Chest pain (angina) is the most common symptom - intensity of the pain varies fromperson-to-person ;
- Typical chest pain - felt under the sternum and is characterized by a heavy or squeezing feeling, it is precipitated by exertion or emotion, and it is relieved by rest or nitroglycerin.
- Atypical chest pain - located in the left chest, abdomen, back, or arm and is fleeting or sharp; unrelated to exercise and is not relieved by rest or nitroglycerin.
- Shortness of breath - long-term lack of blood and oxygen; accompanied by swollen feet and ankles
- Heart attack -the first sign of CHD ; pain is usually severe, lasts longer than the chest pain and is notrelieved by resting or nitroglycerin.
- Electrocardiogram (ECG)
- Exercise stress test
- Echocardiogram ·
- Nuclear scan ·
- Coronary angiography/arteriography –the only certain way to diagnose & assess the extent of CHD
- General treatments include lifestyle changes, medications, and sometimes surgery.
- Beta-blockers -to decrease heart rate and loweroxygen use by the heart
- Cholesterol-lowering medication-Antiplatelet agents, such as aspirin to reduce the risk of blood clots
- Don't smoke
- Eat a low fat, low cholesterol diet
- Eat well-balanced meals (fruits & vegetables)
- Keep blood pressure under control
- Manage stress.
- demyelinating disease involving the white matter of the brain and spinal cord
- occurs more frequently in females than males (2:1 ratio)
- mean age of occurrence: 30 yrs old (range bet 18 and 40)
- Multiple Sclerosis
- evidence of the disease may be found on the surface of the brainstem or along the spinal cord, where myelinated fiber tracts course superficially
- lesions appear as multiple, well-circumscribed, somewhat depressed, glassy, gray-tan, irregularly shaped plaques
- Multiple Sclerosis
- although the cause of MS is unknown, autoimmune mechanisms are considered important in the pathogenesis of this disease
- diagnosis can be very difficult; typically involves the evidence from the person’s history, a clinical examination, and one or more laboratory tests
- blurred or double vision
- muscle weakness in their extremities
- difficulty with coordination and balance
- difficulties with concentration, attention, memory
- Sensory disorders
- Visual complaints
- Spastic weakness of the limbs
- Cerebellar signs
- Bladder dysfunction
- Disorders of mood
- MRI (Magnetic Resonance Imaging) diagnostic tool that currently offers the most sensitive non-invasive way of imaging the brain scanning procedure is very sensitive, and can often create pictures of lesions, or areas of damage, that would be missed by a CT scan.
- Cerebrospinal fluid tested for levels of certain immune system proteins and for the presence of a staining pattern of antibodies called oligoclonal bands.
- Intermittent relapses followed by more or less complete remission.
- Severe disability occurs within a few years in a rare, malignant form of the disease.
- ACTH- used during acute phase.
- Immunosuppressive agents and plasmapheresis.
Patients experience alterations in all functions- vision, mobility and coordination, nutrition, elimination and communication.
Care of the patient with MS requires a total health care team approach.
ROLE OF OMEGA-3 FATTY ACIDS IN HUMAN DIET
OMEGA-3 FATTY ACID
- aka "linolenic acid"
- Polyunsaturated fatty acids
- Important to human health
- Play a crucial role in brain function as well as normal growth and development
- Used in the formation of cell walls, making them supple and flexible,
- Improving circulation and oxygen uptake with proper red blood cell flexibility and function.
MAJOR OMEGA-3 FATTY ACIDS
- ALA (Alpha linolenic acid)
- EPA(Eicosapentanoic acid)
- DHA (Decosahexanoic acid)
MAJOR OMEGA-3 FATTY ACIDS
- ALA (alpha linolenic acid)
- Found in food (flaxseed)
- Key player in immunity, vision ,and cell membranes
- Decrease blood clotting and inflammatory processes
- Deficient include loss of motor coordination, tingling in the extremities, vision impairment, and behavioral changes
- DHA (Decosahexanoic acid)
- Made from ALA
- Found mostly in the brain, retina and in sperm
- Important role in vision
- EPA (Eicosapentanoic acid)
- Abundance in cold-water fishes such as salmon and tuna
- Livestock and Poultry sources
Benefits of Omega-3 Fatty Acids:
- promote cardiovascular health
- increase memory and learning ability
- helps brain & vision
- development of infants
- decreased development of age-related macular degeneration (AMD)
- helps boost immune system (defends against cancer)
- promotes natural joint flexibility and mobility (decreases rheumatoid arthritis)
- reduces symptoms of depression
- reduces risk of dementia, e.g. Alzheimer’s disease
OMEGA-3 FATTY ACID
(US NATIONAL INSTITUTES OF HEALTH RECOMMENDS)
- EPA and DHA - 650 mg/day
- ALA - 2.22g/day
- Omega-3- 4.44 g/day
RISKS OF OMEGA-3 FATTY:
- increased bleeding times
- Cause flatulence and diarrhea
Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under supervision of a healthcare provider
- BLOOD- THINNING MEDICATIONS
- ETRETINATE AND TOPICAL STEROIDS
- CHOLESTEROL-LOWERING MEDICATIONS
- NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
HOW DIET AND LIFESTYLE AFFECT SERUM CHOLESTEROL
What affects cholesterol level?
- Diet. Saturated fat and cholesterol in the food you eat make your blood cholesterol level go up. Saturated fat is the main culprit, but cholesterol in foods also matters. Reducing the amount of saturated fat and cholesterol in your diet helps lower your blood cholesterol level.
- Weight. Being overweight is a risk factor for heart disease. It also tends to increase your cholesterol. Losing weight can help lower your LDL and total cholesterol levels, as well as raise your HDL and lower your triglyceride levels.
- Physical Activity. Not being physically active is a risk factor for heart disease. Regular physical activity can help lower LDL (bad) cholesterol and raise HDL (good) cholesterol levels. It also helps you lose weight. You should try to be physically active for 30 minutes on most, if not all, days.
Types of cholesterol:
Cholesterol is transported around the body in the blood attached to a protein. This fat-protein combination is called a lipoprotein. Lipoproteins can be high density (HDL), low density (LDL) or very low density (VLDL), depending on how much protein there is in relation to fat.
LDL (bad cholesterol)
- This is mostly fat and not much protein.
- LDL causes cholesterol to be deposited in the arteries. High levels of LDL are associated with an increased risk of heart disease.
HDL (good cholesterol)
- mostly protein and not much fat.
- HDL actually helps prevent cholesterol building up in the arteries. Low levels of HDL are associated with an increased risk of heart disease.
A different type of fat, which mostly come from fats in food
Calories that are eaten and not used immediately are converted into triglycerides and transported to fat cells for storage.
They are carried in the blood as very low density lipoproteins (VLDL).
Only about 20% of cholesterol comes directly from the diet - the other 80% is produced by the liver. However, a diet high in saturated fats and cholesterol can cause the liver to produce more LDL ("bad") cholesterol. The amount that diet influences cholesterol levels varies from person to person and is probably an inherited characteristic. Some people who eat high-fat diets have high cholesterol levels; others may have normal or low cholesterol levels.
How Lifestyle affects blood cholesterol
- Weight management
- Physical activity
- Other health conditions such as poorly controlled diabetes, certain kidney and liver diseases and an underactive thyroid gland may also cause cholesterol levels to rise. Some medicines such as beta-blockers, steroids or thiazides (a type of diuretic) may also affect blood lipid levels.
- Healthy eating
- Diet should be low in saturated fats in particular,
- Aim to eat at least five portions of fruit and vegetables each day and low in fat overall
- It's also important to eat plenty of fiber, especially soluble fiber, which is thought to lower cholesterol
- Aim to eat at least five portions of fruit and vegetables each day
- Regular exercise
MYELIN AND MULTIPLE SCLEROSIS
Is the name given to an axon (or a dendrite) of a nerve cell.
Two types of nerve fibers are present in the Central and Peripheral Nervous system:
- Non- Myelinated fibers
- Myelinated fibers
Myelinated Nerve fibers
- This nerve fiber is surrounded by a myelin sheath.
- The myelin sheath is not part of the neuron but is formed by a supporting cell:
- Oligodendrocytes –central nervous system
- Schwann cell –peripheral nervous system
- The myelin sheath is a segmented, discontinuous layer interrupted at regular intervals by the nodes of Ranvier.
- As an impulse moves down a myelinated axon, the impulse JUMPS form Node to Node instead of moving along the membrane.
- These sheaths protect the fibers from abuse and help quicken the transfer of nerve impulses along them, like the electrical wire coating protects the wire within.
- Oligodendrocyte – form and maintain myelin sheaths for 60 nerve fibers (axons)
- Schwann cell – 1 nerve fiber
- Myelination begins at about the 16th week of intrauterine life and continues postnatally until practically all the major nerve fibers are segmented by the time the child is walking.
- It is a lipoproteinous substance constituting the sheaths of various nerve fibers throughout the body and enveloping the axis of myelinated nerves.
- Composed of phospholipids and protein
Major Protein in the Myelin CNS are:
- Myelin basic protein
- Proteolipid protein
Functions of Myelin:
- Myelin acts as an electrical insulator for nerve fibers.
- This white matter coating nerves enables them to conduct impulses between brain and other parts of the body.
- Speeds up transmission of action potentials
- Conditions characterized by a preferential damage to myelin, with relative preservation of axons.
- The clinical deficits are due to the effects of myelin loss on the transmission of electrical impulses along axons.
- This is the most common of the demyelinating disorders.
- Characterized by the degeneration and loss of myelin in the brain and spinal cord.
- The appearance of patches in the white matter of the CNS generally starts in the optic nerve, spinal cord or cerebellum.
What causes MS?
- The cause of MS is unknown.
- Researches suggest that a foreign object such as a virus or an abnormal gene alters myelin or the immune system so that the immune system perceives myelin as an intruder and attacks it.
- After patches of myelin are taken off the axon, oligodendrocytes repair the damage but in the process cause scar tissue (gliotic plaques). These hard plaques then interfere with the flow of electrical impulse that move through the axon while some of the myelin disappears and nerves become stripped of this covering. (demyelinated)
- 225 miles per hour – impulse travelled normally
- If destroyed – lowered down to half the speed or less
Type of symptoms produced depends on:
- Size of sclerotic plaques
- Location of the plaque
- Problems with walking
- Bowel and/or bladder disturbances
- Visual problems
- Changes in cognitive function
- Abnormal sensations such as numbness or "pins and needles"
- Changes in sexual function
- Depression and/or mood swings
Is MS inherited?
- Genetics may play a role in MS.
- European, Eskimos and African essentially do not develop MS.
- Native Indians of North and South America, Japanese and other Asian groups have a low incidence.
- The chance increases in families w/ 1st degree relative that has the disease.
- 1-3% chance – brother, sister or parent
- 30% - identical twin
- 4% - non-identical twin
These statistics suggest that genetics may play a role but other data suggest that environmental factors also have as important role.
The disease is more common in temperate climates (1:2,000) than in tropics (1:10,000)
The onset Of MS is usually at age 20 to 40 years.
ROLE OF OMEGA-6 FATTY ACIDS IN THE HUMAN DIET
Omega-6 Fatty Acids
- Are essential fatty acids.
- They are essential to human health but cannot be made in the body.
- They must be obtained from food.
Dietary sources include:
- Most vegetables oils
- Eggs and Poultry
- Baked goods
- Plant and Animals sources
- Unheated and Unprocessed vegetables oil
- Plant materials like Goose Berry oils
- Raw nuts and seeds, legumes, leafy greens, lean meat, breast milk.
Types of Omega-6 Fatty Acids:
1. Linoleic Acids
- Found in vegetable oils.
- Reduced cardiac arrhythmia's and reduced carotid arteriosclerosis.
- It is converted to gamma-linolenic acid in the body.
Gamma Linoleic acid
- Can be ingested from several plant-based oils including evening primrose.
- Reduced inflammation.
- Further broken down to arachidonic acid.
2. Arachidonic acid
- Consumed directly from meat.
- It is present in the membranes of the body’s cells and is enriched in the brain.
- It is a precursor in the production of eicosanoids: the prostaglandins, thromboxanes, prostacyclin and the leukotrienes.
Health benefits of Omega-6:
- Promote efficient nutrient utilization needed for cardiovascular growth and development.
- Increase the fluidity, or pliability of cell membranes.
- Help keep cells functioning efficiently.
- Promotes healthy energy and vitality.
- Promotes healthy cholesterol level.
- Provide critical support for the healthy cellular uptake of nutrients and cellular export of waste and metabolites.
- Play a crucial role in brain function as well as normal growth and development.
- Stimulate skin and hair growth.
- Maintaining bone health.
- Regulating metabolism.
- Maintaining reproductive capability.
Omega-6 Fatty Acids may be useful for the following purpose:
- Anorexia Nervosa
- Attention Deficit/Hyperactivity Disorder
- Eye Disease
- Menopausal Symptoms
If currently treated with any of the following medications, Omega-6 supplements should be avoided:
- Chemotherapy for cancer
- Nonsteroidal Anti-inflammatory Drugs
- Phenothiazines for schizophrenia
- It is available in supplemental oils.
- For general health, there should be a balance between omega-6 and omega-3 fatty acids; the ratio should be in the range of 1:1 to 4:1.
- A diet that is balanced in Omega-6 as well as omega-3 fatty acids may delay the progression of degenerative brain diseases such as Parkinson’s disease and Alzheimer's disease.
- Dietary balanced between the two major fatty acids, so that the body eicosanoids are balanced omega-6 and omega-3.
Imbalance contributes to long term disease such as:
- Heart disease
For nursing infants, adequate amounts of essential fatty acids are generally supplied in breast milk if the mother is adequately nourished.
For essential fatty acids should be obtained through the diet.
- Omega-6 should not be used if you have a seizure disorder because there have been reports of these supplements inducing seizures.
- Borage seed oil, and other sources of GLA, should not be used during pregnancy because they may be harmful to the fetus and induced early labor.