Module 6 Flashcards
organic compound required in the diet in small amounts for the maintenance of normal metabolic integrity
Vitamins
___ are NOT vitamins
Vitamin D and Niacin
Vitamins that are more dangerous in excess
Fat Soluble Vitamins
What are the Fat-Soluble Vitamins?
vitamin A
vitamin D
vitamin E
vitamin K
- absorption dependent on ileum, bile and pancreas (need fat to absorb vitamins)
- toxicity more common (high intake leads to eventual storage in fatty tissues)
- affected by Malabsorption Syndromes (Cystic Fibrosis, Celiac Sprue, Mineral Oil Intake)
Fat-Soluble Vitamins
- affects mostly white caucasians
- exocrine pancreatic deficiency (lack pancreatic lipase)
- unable to degrade and absorb fat
Cystic Fibrosis
- gluten enteropathy; blunting ot the small intestine’s microvilli
Celiac sprue
compete with the absorption of fat soluble vitamins
Mineral Oil intake
Site for absorption of Iron and Vitamin C
Duodenum
Main site for absorption of Carbohydrates, Fats, Water and Protein
Jejunum
Site for absorption of Fat Soluble Vitamins, Vitamin B12, Intrinsic Factor and Bile salts
Ileum
Absorption of the Fat Soluble Vitamin in what part of the Ileum?
Terminal Ileum
4 Forms of Vitamin A
- Retinol - Vitamin A alcohol
- Retinal - Vitamin A aldehyde
- Retinoic Acid - Vitamin A acid
- Beta Carotene
- found in the gonads; supports gametogenesis in gonads
Retinol
- needed for the eyes to produce rhodopsin needed for night vision
Retinal
- Vitamin A needed for skin degeneration
Retinoic Acid
- type of Retinoic Acid used to treat psoriasis; highly teratogenic
Tretinoin
- type of Retinoic Acid used to treat Acne; highly teratogenic
Isotretinoin
storage form of Vitamin A
retinyl esters
Transport form of Vitamin A
retinol-binding protein (RBP)
Vitamin that is used to treat APML (Acute Promyelocytic Leukemia)
Vitamin A - All-trans retinoic acid
FUNCTIONS
– Retinoic Acid: growth regulators in the epithelium
• All-trans retinoic acid or TRETINOIN
• 13-cis-retinoic acid or ISOTRETINOIN
– Retinol: supports gametogenesis in gonads
– Retinal: present in rod and cone cells for vision
• Fxns as prosthetic group of opsins,
forming rhodopsin and iodopsin
Cells that are found in the liver that stores Fat Soluble Vitamins mainly Vitamin A
Ito Cells
Earliest sign of Vitamin A Deficiency
Night Blindness/Nyctalopia
- Lost of sensitivity to green light leading to Nyctalopia (night blindness): earliest manifestation
- Xerophthalmia: corneal keratinization and ulcerization
- Increased infections
- impotence
- growth retardation
Vitamin A Deficiency
One of the leading causes of blindness in the Philippines esp the poor people
Vitamin A Deficiency
- pseudotumor cerebri (increase ICP): headache, nausea, ataxia, anorexia
- Excessive dryness, desquamation, alopecia
- hepatomegaly
- increased fractures
- teratogenic (neural tube defects, facial malformation, cardiac abnormality)
VITAMIN A EXCESS (Hypervitaminosis A)
false mass in the brain; excess production of CSF
Pseudotumor Cerebri
Vitamin D (Calciferol): Forms
Ergocalciferol
Cholecalciferol vitamin D3, skin, animal sources
Calcitriol 1,25-(OH)2vitamin D3
vitamin D2, milk, plant sources
Ergocalciferol
vitamin D3, skin, animal sources
Cholecalciferol
vitamin D3; synthesize inside the body
Calcitriol 1,25-(OH)2
Precursor form of the Vitamin D
7-dehydrocholesterol
Storage Form of Vitamin D
25-(OH) vitamin D3
Active Form of Vitamin D
1,25-(OH)2 vitamin D3
Site of the hydroxylation (addition of hydroxyl group) in Carbon 25
Liver
Site of the hydroxylation (addition of hydroxyl group) in Carbon 1
Kidney
Remember: Vitamin D
Vitamin D comes from Cholesterol
Starts at the Skin
1st activation: Liver
2nd activation: Kidney
Vitamin D (Calciferol): Function
Responds to hypocalcemia and PTH
end goal = Increase Calcium and Increase PO4
– increase intestinal absorption of calcium
– increase bone deposition/resorption
– increase kidney reabsorption
Effects of PTH in Intestine, Kidney and Bone
Intestine: Indirectly increases calcium and phosphate absorption by increasing Vitamin D metabolite (No Effect)
Kidney: Decreased calcium excretion, increased phosphate excretion
Bone: Calcium and phosphate resorption increased by continuous high concentrations. Low intermittent doses increase bone formation
Effects of Active Vitamin D metabolites
Intestine: Increased calcium and phosphate absorption
Kidney: Increased resorption of Calcium and phosphate but usually net increase in urinary calcium due to effects in GI tract and bone
Bone: Direct effect is increased calcium and phosphate resorption; indirect effect is promoting mineralization by increasing the availability of calcium and phosphate
VITAMIN D DEFICIENCY
- Rickets: in children only, before growth plate closes
- Osteomalacia: in adults only, after growth plate closes
Signs of Rickets
- Short
- Soft Spot on baby’s head is slow to close
- bony necklace (rosary ribs)
- curved bones
- big, lumpy joints
- bowed legs (knees bent out/genu varus)
What causes Rickets/Osteomalacia?
- Lack of Vit D, calcium in diet
- Lack of Sunlight Exposure
- Intestinal Malabsorption
- Chronic Renal Failure
- Target Organ Resistance
- MOST TOXIC VITAMIN
- Hypercalcemia
- Anorexia and nausea
- Thirst
- Stupor
VITAMIN D EXCESS (Hypervitaminosis D)
Manifestation og Hypocalcemia
- Tetany and seizures
- Chvostek’s Sign
- Trosseau’s Sign
- long QT on ECG
Manifestation of Hypercalcemia
- Stones (Urolithiasis)
- Bones (Pain, Osteoporosis)
- Abdominal Groans (Constipation, PUD, Pancreatitis)
- Psychic Overtones (depression, anxiety)
- Psychosis
- Short QT on ECG
Vitamin E (a-Tocopherol): Function
antioxidant in the lipid phase
- protects membrane lipids from peroxidation
- prevent oxidation of LDL decrease atherogenesis
VITAMIN E DEFICIENCY
Dietary deficiency among humans is actually unknown
- RBC fragility hemolytic anemia
- neurologic dysfunction (neuropathy)
- Muscle membrane damage
Least toxic Vitamin
Vitamin E Excess
Vitamin K: Forms
- Phylloquinone/Vitamin K1 - Green vegetables
- Menaquinone/Vitamin K2 -Intestinal Bacteria
- Menadione Synthetic
Vitamin K: Function
for carboxylation of glutamic acid residues in many calcium-binding proteins
– coagulation factors X, IX, VII, II (1972)
– protein C and S
VITAMIN K DEFICIENCY vs VITAMIN K EXCESS
VITAMIN K DEFICIENCY
- rare because vitamin K can be produced by bacteria in the GIT
- Hemorrhagic Disease of the Newborn
• presents as bleeding (including intracranial bleeds)
• neonates at risk because of sterile GIT and low vitamin K
content of breast milk
VITAMIN K EXCESS
- jaundice + hemolytic anemia
CLINICAL CORRELATES (Vitamin K)
Heparin is the time for Peace (Antidote: Protamine Sulfate)
Warfarin is the time for Killing (antidote: Vit K and FFP (Fresh Frozen Plasma))
Water-Soluble Vitamins
- vitamin B1 or Thiamine (thiamine PP)
- vitamin B2 or riboflavin (FAD, FMN)
- vitamin B3 or niacin (NAD+)
- vitamin B5 or pantothenic acid (CoA)
- vitamin B6 or pyridoxine (pyridoxal phosphate)
- vitamin B12 or cobalamin
- vitamin C or ascorbic acid
- biotin
- folate
generally NON-TOXIC compared to the oil-solubles
– excesses just wash out of the body in urine
– Exceptions: vitamin B3, B6 and B12
Water-Soluble Vitamins
- Active Form of Vitamin B1 (Thiamine)
- used as a cofactor in
• Pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and branched chain AA dehydrogenase
• transketolase reactions in the HMP shunt
thiamine pyrophosphate (TPP)
What is the difference between Cofactor, Coenzyme and Prosthetic Groups?
Cofactor - transiently attached
Coenzyme - shuttles of substrate
Prosthetic Groups - Tightly attached to enzyme (permanent)
Vitamin B1 (Thiamine) Deficiency:
– beriberi (dry and wet)
– Wernicke-Korsakoff syndrome
Dry Beriberi vs Wet Beriberi
Dry Beriberi
– dry = no heart failure
– polyneuritis
– symmetrical muscle wasting
Wet Beriberi
– wet = with heart failure
– high-output cardiac failure (dilated cardiomyopathy)
– edema (pulmonary edema)
Wernicke Encephalopathy vs Korsakoff Psychosis
“Weird ACO”
Wernicke Encephalopathy
Ataxia, Confusion, Ophthalmoplegia
“Korny si CHA”
Korsakoff Psychosis
Confabulation, Hallucination, Amnesia
active forms: flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD)
– used as cofactors in redox reactions, as electron carrier
– Has intense yellow color: used as food additive
Vitamin B2 (Riboflavin)
– NO deficiency state but with s/sx
• Stomatitis (inflammation of oral mucosa)
• Cheilosis (inflammation of lips and angle of mouth)
• Seborrheic Dermatitis
• Corneal vascularization
Vitamin B2 (Riboflavin) Deficiency:
active forms: nicotinamide adenine dinucleotide + phosphate (NAD+ and NADP+)
– used as coenzymes in redox reactions, as -> electroncarriers
– Source of ADP-Ribose: for proteins and nucleoprotein in DNA repair
– may be derived from tryptophan using vitamin B6
Vitamin B3 (Niacin)
– Pellagra = 4 Ds
– Diarrhea, Dermatitis, Dementia, Death
Hartnup Disease - dec Tryptophan absorption
Carcinoid Syndrome - inc Tryptophan metabolism
Isoniazid Use - dec Vitamin B6
Vitamin B3 (Niacin) Deficiency
Vitamin B3 (Niacin) Excess
Liver Damage
active form: constituent of Coenzyme A
– used as cofactor for acyl transfers
– component of fatty acid synthase
Vitamin B5 (Pantothenic Acid)
NO deficiency state but with s/sx – dermatitis – enteritis – alopecia – adrenal insufficiency
Vitamin B5 (Pantothenic Acid) deficiency
active form: pyridoxal phosphate – used as coenzyme in AA transamination – used as coenzyme for: • glycogen phosphorylase • cystathionine synthase • ALA synthase – Removes hormone-receptor complex from DNA: stops steroid hormone action – synthesis of niacin from tryptophan
Vitamin B6 (Pyridoxine)
Isoniazid toxicity – INH + pyridoxal phosphate = inactive derivative – peripheral neuropathy – Excess: – intake of > 200 mg/day – gait problems and CNS toxicity
Vitamin B6 (Pyridoxine) deficiency
Vitamin B12 (Cobalamin) structure
cobalt in center of corrin ring
Methylcobalamin vs Cyanocobalamin
Methylcobalamin - contains methyl group
Cyanocobalamin - contains CN
- Binds initially to salivary cobalophilin in the stomach
- needs intrinsic factor for absorption
– IF produced by stomach parietal cells
– absorbed in terminal ileum
Vitamin B12 (Cobalamin)
Vitamin B12 (Cobalamin) 2 active forms
- 5-deoxyadenosylcobalamin: used for methionine synthesis
- homocysteine + N-methyl THF»_space;methionine + THF - methylcobalamin: used for isomerization reactions
methylmalonyl CoA -> succinyl CoA; methylmalonyl mutase
Vitamin B12 (Cobalamin) deficiency
Pernicious Anemia (autoimmune destruction of parietal cells leading to dec IF secretion and decrease vitamin B12 absorption)
Vitamin B12 (Cobalamin) deficiency: early s/sx and late s/sx
early s/sx megaloblastic anemia
late s/sx neuropsychiatric
Diagnostic Test for Pernicious Anemia
Schilling Test, Vitamin B12, anti-IF
structure: pterin ring + para-aminobenzoic acid (PABA) + glutamate residues
– humans cannot synthesize PABA and add glutamate, therefore humans cannot synthesize folate
– should be provided from diet
Folic Acid
- active form of Folic Acid
- used as coenzyme for 1-carbon transfer
• methylation reactions, like synthesis of purines and thymine
tetrahydrofolate (THF)
CLINICAL CORRELATION (FOLIC ACID)
Methotrexate: anti-cancer drug, inhibitis dihydrofalte
reductase of humans
Co-Trimoxazole: an anti-metabolite antibiotic, inhibits both processes in THF synthesis of bacteria:
– Trimethoprim: dihydrofolate reductase
– Sulfamethoxazole: dihydropteroate synthase
Folic Acid Deficiency
– megaloblastic anemia with no neurologic symptoms
• HYPERSEGMENTATION OF NEUTROPHILS (earliest manifestation)
• macrocytic anemia
– Functional folate deficiency in those with increease homocysteine»_space; INCREASE RISK OF M.I.
– neural tube defects
• pregnant mothers must be given 400 mcg folate daily
- used as cofactor for carboxylation reactions
pyruvate carboxylase - pyruvate»_space; oxaloacetate
acetyl CoA caboxylase - acetyl CoA»_space; malonyl CoA
prop’l CoA carboxylase - propionyl CoA»_space; methylmalonyl CoA
Biotin
– induced by avidin in egg whites
• dermatitis
• enteritis
Biotin Deficiency
Vitamin C (Ascorbic Acid) Functions:
- Used as a cofactor in:
• hydroxylation of proline and lysine (collagen synthesis)
• dopamine β-hydroxylase (dopamine to norepinephrine) - reduces Fe3+ to Fe2+ in stomach to h Fe absorption
– Scurvy • loose teeth and sore gums • swollen joints • fragile vessels • anemia
Vitamin C Deficiency
Minerals for Structural Function
Calcium, Magnesium, Phosphate
Minerals Involved in membrane function
Sodium, Potassium
Function as prosthetic groups in enzymes
Cobalt, Copper, Iron, Molybdenum, Selenium, Zinc
Regulatory role or role in hormone action
Calcium, Chromium, Magnesium, Manganese, Sodium, Potassium
Known to be essential, but function unknown
Silicon, Vanadium, Nickel, Tin
Have effects in the body, but essentiality is not established
Fluoride, Lithium
May occur in foods and known to be toxic in excess
Aluminum, Arsenic, Antimony, Boron, Bromine, Cadmium, Cesium, Germanium, Lead, Mercury, Silver, Strontium
SETTING
- industrial exposures (usually via the inhalation of dust)
- children who have ingested large quantities of chips or
flakes of lead-containing paint (PICA)
BIOCHEMICAL EFFECTS
- Replaces normal functional metals of enzymes
- Developmental and neurologic effects maybe due to
replacement of Ca2+ in two regulatory proteins important in the central nervous system and other tissues, Ca2+ calmodulin and protein kinase C
Acute Inorganic Lead Poisoning
PRESENTATION
- acute abdominal colic (lead colic) and CNS changes (acute
encephalopathy)
- high mortality rate
TREATMENT
- prompt chelation therapy is mandatory
Acute Inorganic Lead Poisoning
PRESENTATION
- peripheral neuropathy (wrist-drop), anorexia, anemia,
tremor, weight loss, gastrointestinal symptoms
- in children, growth retardation, neurocognitive deficits, developmental delay
TREATMENT
- removal from the source of exposure
- chelation therapy
- oral SUCCIMER in outpatients
- EDTA +/- DIMERCAPROL in severe cases
- dietary modification (high dietary calcium)
Chronic Inorganic Lead Poisoning (Plumbism)
SETTING
- usually due to tetraethyl lead or tetramethyl lead contained in antiknock gasoline additives
PRESENTATION
- hallucinations, headache, irritability, convulsions, coma
TREATMENT
- decontamination, seizure control
Organic Lead Poisoning
SOURCES
- mercury-containing materials in dental laboratories
- manufacturing of wood preservatives, insecticides and
batteries
- organic mercury compounds are used as seed dressings and fungicides
BIOCHEMICAL EFFECTS
- Heavy metal that binds to many enzymes (often at reactive
sulfhydryl groups in the active site)
Mercury
SETTING
inhalation of inorganic elemental mercury
PRESENTATION
- chest pain, shortness of breath, nausea and vomiting, kidney damage, gastroenteritis, CNS damage
- life-threatening hemorrhagic gastroenteritis followed by
renal failure
TREATMENT
- intensive supportive care
- prompt chelation with oral SUCCIMER or IM DIMERCAPROL
Acute Inorganic Mercury Poisoning
SETTING
- inhalation of mercury vapor
PRESENTATION
- loosening of gums and teeth, gastrointestinal disturbances, and neurologic and behavioral changes (ERETHISM)
TREATMENT
- chelation therapy with SUCCIMER and UNITHIOL
- dimercaprol should not be used
- may redistribute mercury to the CNS
Chronic Inorganic Mercury Poisoning
SETTING
- consumption of fish or grains containing methylmercury
PRESENTATION
- Minamata disease (cerebral palsy, deafness, blindness,
mental retardation)
TREATMENT
- uncertain benefits from chelation therapy
Organic Mercury Poisoning
- Radioactive gas
- May be found in buildings, soil, hot springs, etc.
- 2nd most common cause of lung cancer after cigarette
smoking
Radon
- Study of the qualitative and quantitative requirement of diet necessary to maintain good health
- Concerns with the food people eat and how their bodies use it
Nutrition
Types of Nutrients
- Macronutrients - Carbohydrates, fats, proteins
- Micronutrients - Vitamins, minerals
- Water
Functions of Nutrients
1. Provide energy sources Carbohydrates – primary source of energy Fats – secondary source and storage form Proteins – “back-up” 2. Build tissues (Proteins) 3. Regulate metabolic processes - Vitamins and minerals
- Levels of intakes of energy and nutrients which, on the basis of current scientific knowledge, are considered adequate for the maintenance of health and well being of nearly all healthy persons in the population
- Previously called RDA
RECOMMENDED ENERGY AND NUTRIENT INTAKES (RENI)
National Cancer Institute Dietary Guidelines
- Reduce fat intake to 30 percent of calories or less.
- Increase fiber to 20-30 grams/day with an upper limit of 35 grams.
- Include a variety of fruits and vegetables in the daily diet.
- Avoid obesity.
- Drink alcoholic beverages in moderation, if at all.
- Minimize consumption of salt-cured, salt-pickled, and smoked foods.
A measure of the digestibility a food based on the extent to which it raises the blood concentration of glucose compared with an equivalent amount of glucose or a reference food such as white bread or boiled rice
- Carbohydrates that breakdown quickly during digestion have high glycemic indexes
- Carbohydrates that breakdown slowly, releasing glucose gradually into the blood stream, have low glycemic indexes
GLYCEMIC INDEX
GLYCEMIC INDEX RANGE
Low GI = 55 or less
Medium GI = 56 – 69
High GI = 70 or more
SIGNIFICANCE OF GLYCEMIC INDEX
- Foods with low GI
- Smaller rise in blood glucose level
- Can improve diabetes control
- Makes you feel fuller longer - Foods with high GI
- Help refuel carbohydrate stores after exercise
- Translate the qualitative information contained in the GI into quantitative which can be used to calculate the carbohydrate content of a given portion of food
GL = GI / 100 X CHO (grams per serving)
GLYCEMIC LOAD
- Non-digestible carbohydrate and non-carbohydrate substances for which hydrolytic enzymes are lacking in the human digestive system
- May be acted upon by bacteria in the large intestine producing short-chain fatty acids that serve as fuel for enterocytes and other beneficial intestinal bacterial (prebiotic)
- High intake associated with reduced incidence of diverticulosis, cancer of the colon, cardiovascular disease and diabetes
Dietary Fibers
FUNCTIONS OF DIETARY FIBERS
- Aids in water retention during passage of food along the gut, producing larger, softer stools
- Soluble fibers lower blood cholesterol by binding bile acid and dietary cholesterol
- Slows stomach emptying and delay post-prandial rise in blood glucose with consequent reduction in insulin secretion
Soluble Fiber vs Insoluble Fiber
Soluble fiber
- Retains water and turns to gel during digestion; slows digestion and nutrient absorption from the stomach and intestine
- Found in foods such as oat bran, barley, nuts, seeds, beans, lentils, peas, and some fruits and vegetables.
Insoluble fiber
- Speeds the passage of foods through the stomach and intestines and adds bulk to the stool
- Found in foods such as wheat bran, vegetables and whole grains
TYPES OF DIETARY FIBERS
- Cellulose - Principal structural material in plant cell walls
- Non-cellulose polysaccharide - Hemicellulose, pectin, gums, mucilages, algal substances; Found in fruits, beans, rice
- Lignin - Non-carbohydrate; are phenylpropane polymers derived from higher alcohols; Makes up the woody part of plants
- Carbohydrates may contribute 55-70% of total dietary energy (TDE), 70% of which should come from complex carbohydrate and not more than 10% should come from simple sugars
- Minimum intake of 50-100 g of CHO/day is recommended to prevent ketosis and loss of muscle protein; no upper limit provided energy needs are in balance
- A daily intake of 20-25 g dietary fiber for adults is suggested
RECOMMENDED INTAKE
- Synthetic compound, benzosulfimide
- Linked to the development of bladder cancer in rats
Saccharin
- Dipeptide made up of phenylalanine and aspartic acid
- Provides 4 kcal/gram; 200 x sweeter than sucrose
Aspartame (Nutrasweet, Equal)
- Manufactured by selective chlorination of sucrose, by which 3 –OH groups of sucrose are substituted with chlorine atoms
- Twice as sweet as saccharin, 4x as sweet as aspartame
- Unlike aspartame, is stable under heat and over a broad range of pH conditions
Sucralose (Splenda)
- Has been used as an herbal sweetener for centuries in South America
- Contains a component called stevioside
- 200-300 times sweeter than sugar; provides no calories
- Non-fermentable, maintains heat stability at 95 °C and has a long shelf life; can be added to cooked/baked goods or processed foods and beverages
Stevia
REASONS FOR USE OF SUGAR SUBSTITUTE
- Assist in weight loss
- Regulate blood glucose levels of people with diabetes
- Prevent reactive hypoglycemia
- Dental hygiene - Are not fermented by the microflora of the dental plaque
- Most of the __ in foods occur as triglycerides
- Triglycerides when hydrolyzed yield fatty acids
Fats
Functions of Fats
- Supply a concentrated available fuel for energy production
- Thermal insulation - Layer of fat underneath the skin controls body temperature
- Vital organ protection - Surrounds organs such as kidneys and protect against mechanical injury
- Nerve impulse transmission - Fats surrounding myelinated nerve fibers provide electrical insulation and aids transmission of nerve impulse
- Essential precursor substance for synthesis of many materials required for metabolic function and tissue integrity
* E.g. lipoproteins and cell membranes - Supply essential fatty acids
- Serve as carriers of fat-soluble vitamins
- Food satiety
- Supplies taste and flavor to food; contributes to feeling of satisfaction after eating
- Introduction of hydrogen into available double bonds of unsaturated fats
- Converts liquid fats such as vegetable oils into solid form for use as vegetable shortening or margarines
- Changes cis form of fatty acids in naturally occurring food fats to trans form —> Intake of trans fats can lead to inhibition of essential fatty acid metabolism, elevation of serum lipid levels and modification of membrane properties
Hydrogenation
Recommended intake of Fats
- Recommended intake for Filipinos is 20-30% of total dietary energy (TDE) for all age group, except for infants which is 30-40%
- The lower limit for adult is to promote absorption of vitamin A which has been found to be generally low in the average Filipino diet
- The upper limit is the maximum intake level recommended as a preventive measure against the risk of cardiovascular and other degenerative diseases
(Fat Substitute)
- Minute protein globules from egg white and whey (a milk protein); has 1.3 kcal/gram
- Simulates consistency of fats
- Used in frozen desserts, mayonnaise and salad dressing
- Structure altered by high temperature; cannot be used for cooking and frying
Simplesse
(Fat Substitute)
- Made by adding fatty acids to sucrose molecule (sucrose polyester)
- Cannot be digested by human digestive enzymes or intestinal bacteria, hence yields no energy
- Can be used for frying
- Tends to bind fat-soluble vitamins such as vitamin E reducing its absorption
Olestra
- Made up of amino acids which can be classified into essential and non-essential
*Essential amino acids – cannot be synthesized in the body hence must be obtained from the diet
Histidine Phenylalanine
Isoleucine Threonine
Leucine Tryptophan
Lysine Valine
Methionine
Proteins
Complete vs Incomplete Protein
Complete proteins
- Those that contain all the essential amino acids in sufficient quantity to meet the body’s need
- Includes protein of animal origin: eggs, milk, cheese, meat (an exception is gelatin)
Incomplete proteins
- Deficient in one or more essential amino acids
- Mostly of plant origin: grains, legumes, nuts, seeds
Corn – deficient in Trp and Lys
Wheat – deficient in Lys
Beans – deficient in Met
Functions of Protein
- Supply amino acids for growth and maintenance of body tissues
- Maintain fluid balance
- Plasma proteins especially albumin are necessary for osmotic pressure regulation in capillaries - Contribute to acid-base balance
- Acts as buffers to regulate acid-base balance in blood - Formation of enzymes, hormones and immunoglobulins
- Substrate for gluconeogenesis
- Provide energy when carbohydrates and fats in the diet are not adequate
- Refers to the difference between total nitrogen intake and total nitrogen loss in feces
- Useful measure of general nutritional status
Nitrogen Balance
Positive vs Negative vs Normal Nitrogen Balance
Positive nitrogen balance - Intake of nitrogen exceeds its output; Characterized growing infants and pregnant women
Negative nitrogen balance - Nitrogen output exceeds intake; Occurs following surgery, in advanced cancer
Normal nitrogen balance - Nitrogen intake matches output; Seen in normal adults
MEASURES OF PROTEIN QUALITY
Depends on its content of essential amino acids
- Chemical Score
- Biologic Value
- Net Protein Utilization
- Protein Efficiency Ratio
- Based on percentage of limiting amino acids (tryptophan, lysine, methionine) present in foods in comparison with a standard protein
- Uses egg as standard with a value of 100
Chemical Score
- Percentage of absorbed nitrogen retained in the body, estimated from nitrogen balance study
Biologic Value (BV)
- Product of biologic value and the degree of the foods protein’s digestibility
Net Protein Utilization (NPU)
- Based on the weight gain of a growing test animal divided by its protein intake over a study period of about 10 days
Protein Efficiency Ratio (PER)
PROTEIN QUALITY
- Eggs and milk are high quality proteins
- Meat is also high quality protein
- Proteins from plants are relatively deficient in certain essential amino acids
- Corn deficient in tryptophan and lysine
- Wheat deficient in lysine
- Some beans deficient in methionine
- In a mixed diet, a deficiency of an amino acid in one protein is made up by its abundance in another; such proteins are described as complementary; the proteins of corn and beans combined provides a satisfactory amino acid intake
PROTEIN: RECOMMENDED INTAKE
- 10-15% of TDE
- 1.14 g/kg/day; adjusted for the protein quality of Filipino rice-based diet
- A safe protein intake level for adults is defined as the lowest level of dietary protein intake that will balance the losses of nitrogen from the body in person maintaining energy balance at modest level of physical activity
Units of energy
Kilocalorie – amount of heat required to raise the temperature of 1 liter of water 1oC
Kilojoule – amount of work involved in moving 1 kilogram for 1 meter with the force of 1 newton
1 Kcal = 4.184 KJ
1 MJ = 239 Kcal
(Measurement of Energy)
- Subject is placed in an insulated chamber and body heat released raises the temperature of a layer of water surrounding the chamber
- Expensive and complex; used only in research studies
Direct calorimetry
(Measurement of Energy)
- Estimates energy expenditure by measures the exchange of gases in respiration
- Respiratory Quotient =volume of CO2 produced/ volume of O2 consumed
- One liter of O2 consumed accounts for approximately 20 KJ (4.83 Kcal) of energy expended
Indirect calorimetry
- Number of kilocalories one gram of nutrient yield when oxidized
Carbohydrate = 4 Kcal / g (17 KJ / g) Protein = 4 Kcal / g (17 KJ / g) Fats = 9 Kcal / g (38 KJ / g) Alcohol = 7 Kcal / g (29 KJ / g)
Fuel Factor
- Food intake is influenced by:
- Hunger – physiological drive to eat and is controlled by internal body mechanisms
- Appetite – psychological drive to eat and affected by external food choice mechanisms
- Satiety – state in which there is no longer a desire to eat; controlled by the hypothalamus
ENERGY BALANCE
Anorexigenic substances (Appetite-Inhibiting)
- Cholecystokinin
- Cocaine-amphetamine- related transcript (CART)
- Corticotropin-releasing hormone (CRH)
- Insulin
- Leptin
- Peptide YY
- POMC/α-MSH
- Serotonin
Orexigenic substances (Appetite-Stimulating)
- Agouti
- Agouti-related peptide
- Ghrelin
- Melanin-concentrating hormone
- Neuropeptide Y
- Orexins A and B
Energy expenditure depends on:
- Basal metabolic rate
- Physical activity
- Thermogenic effect of food
- Adaptive thermogenesis
- Energy expenditure necessary to maintain basic physiologic function under standardized conditions; subjects should be at rest, awake and in a warm environment and measurements should be taken at least 12 hours after the last meal
- Energy needed to sustain the metabolic activities of cells and tissues and to maintain circulatory, respiratory, gastrointestinal, and renal processes
- Measurements made early in the morning before the person has engaged in any physical activity and l0 to 12 hours after the ingestion of any food, drink, or nicotine
BASAL METABOLIC RATE
If any of the conditions for the BMR are not met, energy expenditure should be referred to as the ___. In most cases RMR are higher than the BMR by 10% to 20%
Resting metabolic rate (RMR)
FACTORS DETERMINING BMR
- Lean body mass - More lean body mass, higher BMR; Muscles are more metabolically active than adipose tissue
- Body surface area - Greater body surface area, higher BMR; Children has higher BMR than adults
- Gender - Men have higher BMR than women
- Body temperature - Fever increases BMR
- Thyroid hormone - Presence of hyperthyroidism increases BMR
- Age - BMR decreases with age
- Nutritional state - Starvation lowers BMR
- Growth - Growing children have higher BMR than older people
- Varies widely among individuals; largest variable affecting energy expenditure ACTIVITY LEVEL % BMR Sedentary 20% Light 30% Moderate 40% Heavy 50%
PHYSICAL ACTIVITY
- Previously referred to as Specific Dynamic Action
- Energy expenditure due to digestion, absorption and transport of nutrients
- Accounts for about 10% of total energy expenditure
THERMOGENIC EFFECT OF FOOD
- Represents a small portion of energy use
- When environmental temperature is low, it causes increased energy expenditure owing to shivering and non-shivering thermogenesis in animals having brown fat
- Above body temperature, extra energy is expended in cooling
ADAPTIVE THERMOGENESIS
PATHOPHYSIOLOGY
- Protein energy malnutrition (PEM)
Marasmus – deficiency of energy and protein
Kwashiorkor – deficiency of protein - Obesity – excess in body fat due to dietary excess
- Cachexia - wasting syndrome characterized by weight loss, anorexia and malnutrition associated with advanced cancer, HIV infection and other chronic diseases
Body Mass Index (BMI)
- recommended for assessing body fat
BMI = Weight (in kg)/Height 2 (in meter)
ASIA PACIFIC GUIDELINES
Underweight -
CLASSIFICATION OF OVERWEIGHT AND OBESITY
Waist Circumference
- Use to evaluate a patient’s abdominal fat
- Fat located in the abdominal region is associated with greater health risk than peripheral fat (i.e., fat in the gluteal-femoral region)
- Men > 90cm (35 in.)
- Women > 80cm (31 in.)
STEPS IN CALCULATING DIETS
- Estimate the desirable body weight (DBW)
- Determine the reasonable energy allowance of the individual by multiplying his DBW with given values for level of activity
- Determine amount of carbohydrate, protein and fat intake
- Design a practical meal plan taking into consideration a person’s food habits, food behavior and preferences, etc.
METHODS FOR DETERMINING DESIRABLE BODY WEIGHT
- Use of standard tables (FNRI Standard Weight for Filipinos)
- Tannhauser’s Method
- Use of derived formula based on Body Mass Index (BMI)
- Use of the NDAP formula which gives the closest approximation of the desirable BMI as well as the midpoint of FNRI’s range of reference weights
- Measure height in cm, deduct from the measurement the factor 100 and the difference is the DBW in kg. To apply to Filipino stature, deduct 10%
Tannhauser’s Method
Use of derived formula based on Body Mass Index (BMI)
Desirable BMI for men= 22
Desirable BMI for women = 20.8
BMI = wt (kg) / ht (m)2
DBW = desirable BMI x ht (m)2
- A BMI range of 19 – 24.9 is considered normal
Use of the NDAP formula which gives the closest approximation of the desirable BMI as well as the midpoint of FNRI’s range of reference weights
- DBW for men 5 feet tall is 112 lbs. Add (subtract) 4 lbs for every inch above (below) 5 feet
- DBW for women 5 feet tall is 106 lbs. Add (subtract) 4 lbs for every inch above (below) 5 feet
COMPUTING FOR TOTAL ENERGY ALLOWANCE
ACTIVITY - Kcal/kg DBW/day
Bed rest but mobile (hospital patients) - 27.5
Sedentary (mostly sitting) - 30.0
Light (tailor, nurse, physician, jeepney driver - 35.0
Moderate (carpenter, painter, heavy housework) - 40.0
Very active (swimmer, lumberman) - 45.0
- is accomplished with the aid of hydrolase enzymes of the digestive tract that catalyze the hydrolysis of proteins to amino acids, starches to monosaccharides, and triacylglycerols to monoacylglycerols, glycerol, and fatty acids
Digestion
(Carbohydrate digestion)
- 99.5% water; pH 6.8
- contains mucin, a glycoprotein which acts as a lubricant
- vehicle for excretion of certain drugs (ethanol, morphine) and inorganic ions
- amylase hydrolyzes starch and glycogen by digesting (1-4) glycosidic bonds but is inactivated at pH
Saliva
- The increase in blood glucose after a test dose of a carbohydrate compared with that after an equivalent amount of glucose (as glucose or from a reference starchy food) is known as the ___.
- Glucose and galactose have an index of 1 (or 100%), as do lactose, maltose, isomaltose, and trehalose
- Foods that have a low glycemic index are considered to be more beneficial since they cause less fluctuation in insulin secretion
glycemic index
The hydrolysis of starch is catalyzed by __, which catalyze random hydrolysis of α(1 → 4) glycoside bonds, yielding dextrins, then a mixture of glucose, maltose, and maltotriose and small branched dextrin.
salivary and pancreatic amylases
The disaccharidases, maltase, sucrase-isomaltase (a bifunctional enzyme catalyzing hydrolysis of sucrose and isomaltose), lactase, and trehalase are located on the __, where the resultant monosaccharides and those arising from the diet are absorbed.
brush border of the intestinal mucosal cells
__ occurs among the Inuit, leading to sucrose intolerance,
with persistent diarrhea and failure to thrive when the diet contains sucrose.
Congenital deficiency of sucraseisomaltase
__ are absorbed by a sodium-dependent process. They are carried by the same transport protein (SGLT 1) and compete with each other for intestinal absorption
Glucose and galactose
Because they are not actively transported, fructose and sugar alcohols are only absorbed down their concentration gradient, and after a moderately high intake, some may remain in the intestinal lumen, acting as a substrate for bacterial fermentation. Large intakes of fructose and sugar alcohols can lead to __
osmotic diarrhea
The major lipids in the diet are triacylglycerols and, to a lesser extent, phospholipids. These are hydrophobic molecules and have to be hydrolyzed and emulsified to __ before they can be absorbed.
very small droplets(micelles)
The fat-soluble vitamins, A, D, E, and K, and a variety of other lipids (including cholesterol and carotenes) are absorbed dissolved in the lipid micelles. Absorption of carotenes and fat-soluble vitamins is impaired on a __
very low fat diet
Hydrolysis of triacylglycerols is initiated by __, which attack the sn-3 ester bond forming 1,2-diacylglycerols and free fatty acids, which act as emulsifying agents.
lingual and gastric lipases
- is secreted into the small intestine and requires a further pancreatic protein, colipase, for activity.
- It is specific for the primary ester links—ie, positions 1 and
3 in triacylglycerols—resulting in 2-monoacylglycerols and
free fatty acids as the major end products of luminal triacylglycerol digestion. - Inhibitors of __ are used to inhibit triacylglycerol hydrolysis in the treatment of severe obesity
Pancreatic lipase
- in the intestinal lumen hydrolyzes monoacylglycerols, but they are poor substrates, and only ∼25% of ingested triacylglycerol is completely hydrolyzed to glycerol and fatty acids before absorption
Pancreatic esterase
- formed in the liver and secreted in the bile, permit emulsification of the products of lipid digestion into micelles together with dietary phospholipids and cholesterol secreted in the bile (about 2 g/d) as well as dietary cholesterol (about 0.5 g/d)
- remain in the intestinal lumen, where most are absorbed from the ileum into the enterohepatic circulation
Bile salts
- are less than 1 μm in diameter, and soluble, so they allow the products of digestion, including the fat-soluble vitamins, to be transported through the aqueous environment of the intestinal lumen to come into close contact with the brush border of the mucosal cells, allowing uptake into the epithelium.
Micelles
Within the intestinal epithelium, 1-monoacyglycerols are hydrolyzed to fatty acids and glycerol and 2 monoacylglycerols are reacylated to triacylglycerols via the __
monoacylglycerol pathway
Glycerol released in the intestinal lumen is absorbed
into the hepatic portal vein; glycerol released within the epithelium is reutilized for triacylglycerol synthesis via the __
normal phosphatidic acid pathway
Long-chain fatty acids are esterified to yield to triacylglycerol in the mucosal cells and together with the other products of lipid digestion, secreted as chylomicrons into the lymphatics, entering the bloodstream via the __
thoracic duct
Short- and medium-chain fatty acids are mainly absorbed into the hepatic portal vein as __.
free fatty acids
- (in which the B ring is saturated) compete with cholesterol for esterification, but are poor substrates, so that there is an increased amount of unesterified cholesterol in the mucosal cells.
- effectively inhibit the absorption of not only dietary cholesterol, but also the larger amount that is secreted in the bile, so lowering the whole body cholesterol content, and hence the plasma cholesterol concentration.
Plant sterols and stanols
__ are resistant to digestion because few peptide bonds are accessible to the proteolytic enzymes without prior denaturation of dietary proteins (by heat in cooking and by the action of gastric acid).
Native proteins
The __ Na+-independent facilitative transporter allows fructose, as well as glucose and galactose, to be transported down their concentration gradients. Exit from the cell for all sugars is via the GLUT 2 facilitative transporter.
GLUT 5
- The efficiency of starch digestion is only 70% to 90%
- Plant polymers, including cellulose, hemicelluloses, inulin, and pectin (seen in apple skin) are resistant to human digestive enzymes
POORLY DIGESTED CARBS
- begins in the stomach
- gastric juice has a pH of 1.0 and is 97-99% water
- parietal (oxyntic) cells secrete HCl to denature protein and kill bacteria
- Parietal cells also secrete intrinsic factor for Vit B12 absorption from the ileum
- Pepsinogen —–> Pepsin
- In the duodenum, chyme from the stomach is neutralized and then alkalinized
Protein Digestion
- An __ often follows the ingestion of a meal because of the formation of bicarbonate in the process of HCl secretion
- HCl secretion is driven by the H+ K+ ATPase
- HCO3 passes into the plasma in exchange for chloride
alkaline urine
(Protein Digestion)
In the pancreas there are 4 endopeptidases:
Trypsin – digests peptide bonds of basic amino acids
Chymotrypsin – attacks peptide bonds of uncharged amino acids
Elastase – attacks peptide bonds next to glycine, alanine, and serine (small amino acids)
Pepsin – specific for peptide bonds formed by aromatic amino acids or dicarboxylic a. acids
Activation of __ is due to enterokinase, secreted by the intestinal mucosa. Once trypsin is formed, it activates chymotrypsinogen, proelastase, and procarboxypeptidase.
trypsinogen to trypsin
(Protein Digestion)
__ secrete aminopeptidase and dipeptidases to complete protein digestion to its final amino acid products. Amino acids are then rapidly absorbed from the intestine into the portal circulation
Intestinal glands of Brunner and Lieberkuhn
(Protein Digestion)
The __ of amino acids are actively transported across the intestine from the mucosa to the serosa with the help of Vit B6 (Pyridoxal phosphate)
L-isomer
Amino acids are transported through the brush border through Na-dependent mechanisms. This usually happens in the __
duodenum
Shorter FA’s are transported in the portal venous blood unesterified. Of the plant sterols, only __ is absorbed from the intestine
ergosterol (Provitamin D)
__ catalyzes the hydrolysis of cholesteryl esters, which are absorbed from the intestine in nonesterified form
Cholesteryl ester hydrolase or cholesterol esterase
__ are responsible for dietary nucleic acid digestion
Ribonuclease and deoxyribonuclease
__ hydrolyzes the ester bond in the 2 position of glycerophospholipids to form lysophospholipids, which aid in emulsification of lipids
Phospholipase A2
(Site of Absorption)
Monosaccharides and Dissacharides; Monoacylglycerols, fatty acids, glycerol, cholesterol; Amino Acids, Peptides Vitamins, Folate Electrolytes, Iron, Calcium, Water
Jejunum
(Site of Absorption)
Bile acids
Vitamin B12
Electrolytes
Water
Ileum
Measurement of the ratio of the volume of carbon dioxide
produced: volume of oxygen consumed __is an indication of the mixture of metabolic fuels being oxidized.
(respiratory quotient, RQ)
One of the metabolic reactions to a major trauma, such as a
burn, a broken limb, or surgery, is an increase in the net catabolism of tissue proteins, both in response to cytokines and glucocorticoid hormones, and as a result of excessive utilization of threonine and cysteine in the synthesis of __.
acute-phase proteins
Prolonged bed rest results in considerable loss of protein because of atrophy of muscles. Protein catabolism may be increased in response to cytokines, and without the stimulus of exercise it is not completely replaced. Lost protein is replaced during __, when there is positive nitrogen balance
convalescence
- are chemical substances produced by specialized tissues and secreted into blood, in which they are carried to target organs and triggers specific biological functions
- is a non-nutrient chemical, intercellular messenger that is effective at micromolar concentrations or less (high efficiency)
Hormones
Hormone Synthesis
Hormones synthesized in discrete organs
- Thyroid (triiodothyronine),
- Adrenal (glucocorticoids and mineralocorticoids),
- Pituitary (TSH, FSH, LH, growth hormone, prolactin, ACTH)
Hormones produced in specialized cells within other organs
- Small intestine (glucagon-like peptide)
- Thyroid (calcitonin)
- Kidney (angiotensin II)
Synthesis of some hormones requires the parenchymal cells of more than one organ
- Skin, liver, and kidney are required for the production of 1,25(OH)2-D3 (calcitriol)
- communicates to distant tissues through blood-carried chemicals
- Acts through chemical messengers (hormones) carried in the circulation by secretion into blood and extracellular fluid
- Cells must bear a receptor for the secreted hormone to respond
Endocrine system
- Proteins or glycoproteins
- Specifically binds a hormone and produces a biologic action after binding
- Have high specificity
- May be found on the plasma membrane or inside the nucleus of the cell
Receptors
Concentration: Very low (thousands/cell) Binding affinity: High (pmol/L to nmol/L range) Binding specificity: Very high Saturability: Yes Reversibility: Yes Signal transduction: Yes
Receptors
Concentration: Very high (billions/ μL) Binding affinity: Low (μmol/L range) Binding specificity: Low Saturability: No Reversibility: Yes Signal transduction: No
Transport Proteins
Receptors and Target Cells
Hormone usually affects only target cells
- Responds to a hormone because it bears receptors
Receptors are either on the cell surface or inside the cell
- Recognize a unique binding site in the hormone
Classification of Hormones by Receptor Location
- Hormones that bind to cell surface receptors
2. Hormones that bind to intracellular receptors
Classes of Hormones: Proteins and Peptides; catecholamines and eicosanoids (water soluble)
Principle Mechanism of Action: Generation of second messengers which alter the activity of other molecules - usually enzymes - within the cells
Cell surface Receptors (Plasma membrane)
CLasses of Hormones: Steroids and thyroid hormones (Lipid soluble)
Principle Mechanism of Action: Alter transcriptional activity of response genes
Intracellular Receptors (cytoplasm and/or nucleus)
Structure of Cell Surface Receptors
Integral membrane proteins and have three basic domains:
- Extracellular domains: residues exposed to the outside of the cell interact with and bind the hormone (ligand-binding domain)
- Transmembrane domains: Hydrophobic stretches of amino acids in the lipid bilayer that anchor the receptor in the membrane
- Cytoplasmic or intracellular domains: Tails or loops of the receptor within the cytoplasm interact with other molecules to generate Second messengers and transduction of the hormonal signal
Hormones undergo different actions:
Endocrine action: the hormone is distributed in blood and binds to distant target cells
Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood
Autocrine action: the hormone acts on the same cell that produced it
Types of Hormone Actions
- Autocrine - secreted by cells in a local area and influences the activity of the same cell from which it was secreted; Eg Prostaglandin
- Paracrine - Produced by wide variety of tissues and secreted into tissue spaces; has a localized effect on adjacent cells; Eg Histamine and Prostaglandin
- Hormone - Secreted into the blood by specialized cells; travels by the blood to the target tissues; Eg Thyroxine
- Neurohormone - Produced by neurons and functions like hormones. Eg Oxytocin, Antidiuretic Hormone
Hormone can change its target cells by:
- activation of enzymes
- Modulation of gene expression
Hormones can be classified according to:
- Chemical composition
- Solubility properties
- Location of receptors
- Nature of the signal used to mediate hormonal action
TYPES: \_\_ SOLUBILITY: Lipophilic TRANSPORT PROTEINS: Yes PLASMA HALF-LIFE: Long (hours to days) MEDIATOR: Intracellular RECEPTOR: Receptor-hormone complex
Steroids, iodothyronines, calcitriol, retinoids
TYPES: \_\_ SOLUBILITY: Hydrophilic TRANSPORT PROTEINS: No PLASMA HALF-LIFE: Short (minutes) MEDIATOR: Plasma membrane RECEPTOR: Second messengers: cAMP, cGMP, Ca2+, metabolites of complex phosphoinositols, kinase cascades
Polypeptides, proteins, glycoproteins, catecholamine
- Nonsteroid hormones (water soluble) do not enter the cell but bind to plasma membrane receptors, generating a chemical signal (second messenger) inside the target cell
- Second messengers activate other intracellular chemicals to produce the target cell response
Second Messenger Systems
Epinephrine and Norepinephrine, Glucagon, Luteinizing Hormone, Follicle Stimulating Hormone; Calcitonin, PTH, ADH
Cyclic AMP
Insulin, Growth Hormone, Prolactine, Oxytocin, Erythropoietin, Several Growth Factors
Protein Kinase Activity
Epinephrine and Norepinephrine, ADH, Gonadotropine-Releasing Hormine, Thyroid Releasing Hormone
Calcium and/or Phosphoinositides
Atrial Naturetic Hormone, Nitric Oxide
Cyclic GMP
Hormones that bind to cell surface receptors: Second messenger is cAMP
- α2-Adrenergic catecholamines
- β-Adrenergic catecholamines
- Adrenocorticotropic hormone
- Antidiuretic hormone
- Calcitonin
- Chorionic gonadotropin, human
- Corticotropin-releasing hormone
- Follicle-stimulating hormone
- Glucagon
- Lipotropin
- Luteinizing hormone
- Melanocyte-stimulating hormone
- Parathyroid hormone
- Somatostatin
- Thyroid-stimulating hormone
- is a nucleotide generated from ATP through the action of ADENYLATE CYCLASE.
- Elevated concentrations of cAMP causes activation of a cAMP-dependent protein kinase called protein kinase A
- Protein kinase A (inactive) becomes active when it binds cAMP
- Upon activation, protein kinase A phosphorylates other proteins which alters the cell’s state
e. g. Glucagon
Cyclic AMP Second Messenger Systems
- binds its receptor in the plasma membrane of target cells (hepatocytes)
- Bound receptor interacts with G proteins, turns on adenylate cyclase
- Activated adenylate cyclase convert ATP to cyclic AMP - ↑ intracellular concentration of cAMP
- ↑cAMP in the cytosol make it probable that protein kinase A will be bound by cAMP making it catalytically active
- Active protein kinase A adds phosphates to other enzymes, changing the conformation and modulate the catalytic activity
Glucagon
Levels of cAMP ↓ due to __
destruction by cAMP phosphodiesterase and the inactivation of adenylate cyclase
- Analogous to the cAMP pathway
- Synthesized from GTP by a membrane-bound form of GUANYLATE CYCLASE
- Activates cGMP-dependent protein kinase or protein kinase G
- Action also terminated by PHOSPHODIESTERASE
CYCLIC GUANOSINE MONOPHOSPHATE
Unlike cAMP which affects a wide variety of processes, cGMP functions as a specialized messenger, being involved in:
- smooth muscle relaxation
- platelet aggregation
- visual system
- __, all cause smooth muscle relaxation and are potent vasodilator
- These agents increase cGMP by activating the soluble form of guanylyl cyclase, and inhibitors of cGMP phosphodiesterase (the drug sildenafil[Viagra], for example) enhance and prolong these responses
Nitroprusside, nitroglycerin, nitric oxide, sodium nitrite, and sodium azide
Hormones that bind to cell surface receptors: 2nd messenger is Calcium or phosphatidylinositols (or both)
- Acetylcholine (muscarinic)
- α1-Adrenergic catecholamines
- Angiotensin II
- Antidiuretic hormone (vasopressin)
- Cholecystokinin
- Gastrin
- Gonadotropin-releasing hormone
- Oxytocin
- Platelet-derived growth factor
- Substance P
- Thyrotropin-releasing hormone
- Many receptors respond to hormones by activating a membrane-bound phophodiesterase called __
- Activated Phospholipase C subsequently cleaves membrane-bound phophatidylinositol 1,4,5-trisphosphate, releasing two fragments (inositol 1,4,5-trisphosphate and diacylglycerol)
- Inositol 1,4,5-trisphosphate (IP3) binds to receptors on the endoplasmic reticulum, causing a rapid release of calcium from intracellular stores
Phospholipase C
Released calcium ions permits the formation of a calcium-calmodulin complex that mediates a wide variety of effects
- __ is a protein that acts as a mediator of calcium-linked effects in the cell
- Structurally and functionally related to troponin C, which mediates the role of calcium in skeletal and cardiac muscle contraction
Calmodulin
IP3 is a short-lived signal and is inactivated to __
inositol 1,4-bisphosphate and inositol 1-phosphate
__ activates protein kinase C, an enzyme that phosphorylates proteins
Protein kinase C requires calcium for maximum activity
DAG and IP3 act synergistically to cause increased phosphorylation of proteins
Diacylglycerol (DAG)
Hormones that bind to cell surface receptors: 2nd messenger is a Kinase or Phosphatase cascade
- Chorionic somatomammotropin
- Epidermal growth factor
- Erythropoietin
- Fibroblast growth factor
- Growth hormone
- Insulin
- Insulin-like growth factors I and II
- Nerve growth factor
- Platelet-derived growth factor
- Prolactin
- e.g. Insulin
- Hormone binds to cell surface receptors resulting in a conformational change that activates kinase in the cytoplasm
- Activated receptor phosphorylates itself and phosphorylates enzymes (Tyrosine kinase) that become activated or inactivated
- Tyrosine kinases leads to modulation of target proteins – places phosphates on Tyrosine residues of target cells
Tyrosine Kinase Second Messenger Systems
- Steroid and thyroid hormone receptors are composed of a single polypeptide chain with three distinct domains:
- Amino-terminus: Involved in activating or stimulating transcription
- DNA binding domain: Amino acids in this region are responsible for binding of the receptor to specific sequences of DNA
- Carboxy-terminus or Ligand-binding domain: region that binds hormone
Intracellular Receptors
Hormones that bind to Intracellular receptors
- Androgens
- Calcitriol (1,25[OH]2-D3)
- Estrogens
- Glucocorticoids
- Mineralocorticoids
- Progestins
- Retinoic acid
- Thyroid hormones (T3 and T4)
- Most hormones are Polypeptides or Glycoproteins
- Adrenal Steroid hormones (Synthesized from cholesterol)
- Catecholamine Hormones (Derived from Tyrosine; Thyroid and the Adrenal medullary hormones)
Hormone Composition
Hormone Receptor (first messenger)
- Binds to the plasma membrane at a specific site
- Receptor protein changes shape and activates theG protein
Effector Enzyme
- G proteincomplex activatesadenylate cyclase
- Adenylate cyclasebreaksGTPtoGDP
- Generatessecond messengercyclic-AMPfromATP
Cyclic-AMP (cAMP) moves around the cell triggering chemical reactions with protein kinases
Hormone Signalling Action: cAMP
Hormone Receptor (first messenger)
- Binds to the plasma membrane
- Receptor protein changes shape and can bind withG protein
- G protein bindswithGTPreplacingGDP
Effector Enzyme
- G protein-GTPcomplex activatesPhospholipase(PhospholipasebreaksGTP toGDP)
- PIP2 (phosphatyidyl inositol biphospate)intodiacylglycerol andIP3(inositol triphosphate)
Second Messenger
- Diacylglycerol (DAG)activates protein kinase
- IP3releases Ca+
Third messenger
- Ca+ activates enzymes
Hormone Signalling Action:PIP-Calcium
- are synthesized in ER as the prohormone, transferred to the Golgi and packaged into secretory vesicles for export
- Half-life of circulating is only a few minutes
- Several important __ hormones are secreted from the pituitary gland
The Anterior pituitary secretes:
Luteinizing hormone and Follicle stimulating hormone, Prolactin, Adrenocorticotrpic hormone (ACTH), Growth hormone
The Posterior pituitary gland secretes: Antidiuretic hormone (Vasopressin) and Oxytocin
Peptide hormones
__ are produced by different organs and tissues including:
- Heart (Atrial-natriuretic peptide (ANP) or Atrial natriuretic factor (ANF)
- Pancreas (Insulin and Somatostatin)
- Gastrointestinal tract (Cholecystokinin, Gastrin)
- Fat stores (Leptin)
Peptide hormones
- cannot cross the cell membrane
- bind with a protein on the outside of the cell membrane
- Tyrosine derivatives
Thyroid hormones
*2 tyrosine with the incorporation of 3 or 4 iodine atoms
*Catecholamines (Epinephrine and Norepinephrine)
*Half life: few days
Tryptophan (Serotonin and Melatonin)
Glutamic acid (Histamine)
Amino Acids Derivatives
- Stored as their precursor derivative cholesterol
- Rate-limiting step: conversion of cholesterol to pregnenolone
- Enzymesare needed to convert cholesterol into a steroid hormone
- Bounded to a plasma protein and diffuses easily from the cell membranes
- E.g Cortisol and Testosterone
Steroid Hormones
- Thin barrier separating inside of cell (cytoplasm) from outside environment or internal compartment of organelles from the other cell
- Composed of lipids, proteins and carbohydrate-containing molecules
- Phosphoglycerides – major lipids, but sphingolipids and cholesterol are also present
- Basic structure: Phospholipid bilayer
- Amphipathic in nature - contains both hydrophilic heads and hydrophobic tails
Plasma membrane
Plasma membrane: Functions
- Isolate and protect cell’s contents from outside environment
- Regulate exchange of substances between inside and outside of cell
- Communication and recognition with other cells
- Responds to environment
Plasma Membrane
Glycocalyx – short chains of carbohydrates attached to proteins and lipids extending in the aqueous media
Glycerol based-lipids contain a glycerol backbone and phosphatidic acid, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phophotidylethanolamine, phosphatidylserine, cardiolpin
Spihingosine-based lipid – sphongomyelin
Cholesterol is present maintains membrane fluidity
Fluidity of membrane determined by:
Unsaturated fatty acids – liquid at room temp
Chain length of fatty acids – shoter chains = more fluid
Lipid-soluble substances vs Water-soluble substances
Lipid-soluble substances (e.g., O2, CO2, steroid hormones)
cross cell membranes easily because these dissolve in the hydrophobic lipid bilayer
Water-soluble substances (e.g., Na+, Cl-, glucose, H2O)
cannot dissolve in the lipid of the membrane, but may cross through water-filled channels, pores or carriers
- represents the membrane structure
- Fluid because lipids and proteins can move laterally
- As temperatures drop, liquid membrane solidify
- Saturated fatty acid tails - more solid than unsaturated fatty acid tails
- Cholesterol found in membrane helps with fluidity of membrane
- Membranes need to be fluid to work properly - systems in place to help keep it fluid
“Fluid mosaic model”
Integral proteins vs Peripheral proteins
Integral proteins
- Anchored, embedded in the cell membrane through hydrophobic interactions
- May span the cell membrane
- Ex: ion channels, transport proteins, receptors, and guanosine 5′-triphosphate (GTP)-binding proteins (G proteins)
Peripheral proteins
- Not imbedded in the cell membrane
- Not covalently bound to membrane components
- Loosely attached to the cell membrane by electrostatic interactions
- Provides mechanical support e.g. spectrin
Functions of Proteins in cell membrane
- Maintain shape of the cell
- Act as enzymes that catalyze biochemical reaction
- Receptor Protein - Trigger cell activity when molecule from outside environment binds to protein; Mediators that aid receptor-ligand complex
- Recognition Proteins -Allow cells to recognize / attach to one another
- Glycoproteins: Proteins with attached carbohydrate groups
- Transport Proteins - Regulate movement of hydrophilic molecules through membrane
- Channel Proteins (e.g. Na+ channels)
- Carrier Proteins ( e.g. glucose transporter )
Selectively interacts with specific molecule or ion so that it can cross the plasma membrane. the inability of some persons to use energy for sodium-potassium transport has been suggested as cause of their obesity
Carrier Proteins
is shaped in such a way that a specific molecule can bind to it. Pygmies are short, not because they do not produce enough growth hormone, but because their plasma membrane growth hormone receptors are faulty and cannot interact with growth hormone
Receptor Proteins
Allows a particular molecule or ion to cross the plasma membrane freely. Cystic fibrosis, an inherited disorder, is caused by faulty Chloride (Cl-) channel; a thick mucus collects in airways and in pancreatic liver and ducts
Channel Proteins
Catalyzes a specific reaction. The membrane protein adenylate cyclase is involved in ATP metabolism. Cholera bacteria release a toxin that interferes with the proper functioning of adenylate cyclase; sodium ions and water leave the intestinal cells and the individual dies from severe diarrhea
Enzymatic Protein
- Requires no energy nor carriers
- Substances move down concentration gradients (“downhill”)
- Ex: A. Simple Diffusion - Small molecules pass directly through the phospholipid bilayer depends on:
Molecule size
Concentration gradient
Lipid solubility
Passive Transport
- Includes Facilitated diffusion and Primary and Secondary active transport
- Exhibits: Stereospecificity, saturation, competition
- Requires binding to channel or carrier proteins (e.g. ions, amino acids, sugars)
Carrier-mediated transport
- Movement of molecules from a region of high concentration to an area of low concentration “downhill”
- Faster than simple diffusion
- Does not require an input of chemical energy (Passive)
- Uses channel proteins or carrier proteins ( e.g. ions, amino acids, sugars)
Facilitated diffusion
- Occurs against an electrochemical gradient (“uphill”).
- Requires direct input of metabolic energy in the form of ATP and therefore is active
- Carrier-mediated exhibits stereospecificity, saturation, and competition
Ex:
a. Na+ K+-ATPase
b. Ca2+-ATPase (or Ca2+ pump)
c. H+ K+-ATPase (or proton pump)
Primary active transport
- Transport of 2 or more solutes is coupled
- 1 solute (usually Na+) is transported “downhill” and provides energy for the “uphill” transport of the other solute(s).
- Energy comes indirectly from Na+ gradient maintained by Na+ K+-ATPase
- Cotransport, or symport – solutes move in the same direction
Ex: Na+-glucose cotransport in the small intestine and Na+-K+-2Cl- cotransport in the renal thick ascending limb - Countertransport, exchange, or antiport – solutes move in opposite directions
Ex: Na+-Ca2+ exchange and Na+-H+ exchange
Secondary active transport
– transmembrane proteins forming a pore for ions that opens/closes in response to a stimulus
- Voltage gated channels – responds to voltage change
- Ligand gated channels – binding of a ligand to a protein
- Phosphorylation-gated channels – covalent change (phosphorylation) on the protein e.g. Cystic fibrosis
Gated channels
- Exocytosis
- Endocytosis
Vesicular transport
- Cellular secretion
- Transport vesicle buds from Golgi apparatus
- When membranes meet and fuses - material is let out to outside of cell
- E.g. Insulin from beta cells of the pancreas
Exocytosis
- Cell brings in macromolecules and matter by forming new vesicles from plasma membrane
- Membrane is inwardly pinched off and vesicle carries material to inside of cell
Endocytosis
- “Cell eating” - cell engulfs particle by extending pseudopodia around it, packaging it in a large vacuole
- Contents of vacuole are digested when vacuole fuses with lysosome
Phagocytosis
- “Cell drinking”
- Cell creates vesicle around droplet of extracellular fluid
Pinocytosis
- specific particles, recognition
Receptor-mediated endocytosis
- Portion of the brain located underneath the thalamus contaning nuclei and serves to link the nervous system to the endocrine system via the pituitary gland (hypophysis)
- Found in all vertebrate nervous systems
- responsible for certain metabolic processes and other activities of the autonomic nervous system
- body temperature, Hunger, parenting and attachment behaviors, Thirst, fatigue, sleep, circadian rhythms
Hypothalamus
Temperature regulation
Anterior hypothalamus - response to heat
Posterior hypothalamus - response to cold
- Neuroendocrine control of Catecholamines
- Limbic areas concerned with emotion
Dorsal and posterior hypothalamus
- Neuroendocrine control of Vasopressin
- Osmoreceptors, “volume receptors”
Supraoptic and paraventricular nuclei
- Neuroendocrine control of Oxytocin
- Touch receptors in breast, uterus, genitallia
Supraoptic and paraventricular nuclei
- Neuroendocrine control of TSH via TRH
- Temperature receptors in infants
Paraventricular nuclei and neighboring areas
- Neuroendocrine control of ACTH and B-lipotropin via GnRH
- Limbic system (emotional stimuli); reticular formation (systemic stimuli); hypothalamic and anterior pituitary cells sensitive to circulating blood cortisol level; suprachiasmatic nuclei (diurnal rhythm)
Paraventricular nuclei
- Neuroendocrine control of FSH and LH via GnRH
- Hypothalamic cells sensitive to estrogens, eyes, touch receptors in skin and genitalia of reflex ovulating species
Preoptic areas; other areas
- Neuroendocrine control of Prolactin via PIH and PRH
- Tough receptors in breast, other unknown receptors
Arcuate nucleus, other areas (hypothalamus inhibit secretion)
- Neuroendocrine control of Growth hormone via somatostatin and GRH
Periventricular Nucleus
Thirst
Lateral superior thalamus
Hunger
Ventromedial, arcuate and paraventricular nuclei; lateral hypothalamus
Sexual Behavior
Anterior Ventral Hypothalamus plus in the male piriform cortex
Defensive reactions (fear, rage)
Diffuse, in limbic systam and hypothalamus
Control of body rhythms
Suprachiasmatic nuclei
- The secretion of anterior pituitary hormones is regulate by some six sets of releasing factors that originate in the hypothalamus
- Many of these releasing factor hormones also function as - neurotransmitters or neuromodulators
HYPOTHALAMIC HORMONES
Pituitary Control (Anterior Lobe vs Posterior Lobe)
Anterior lobe
- hypothalamus acts as an endocrine gland
- sent from the hypothalamus to the anterior pituitary via the portal vein
Posterior lobe
- hormones synthesized in the hypothalamus and transported
- Nerve impulses towards posterior pituitary cause release of vesicles into the blood
- Thyroliberin; Peptide to 3 aminor acids
- simplest of the hypothalamic neuropeptides
- consists essentially of three amino acids glutamic acid-histidine-proline
- Produced in medial neurons of the paraventricular nucleus
- synthesized as a 242-amino acid precursor polypeptide that contains 6 copies of the sequence -Gln-His-Pro-Gly-, flanked by Lys-Arg or Arg-Arg seqences
- multiple steps produce 6 copies of the mature TRH molecule per precursor molecule for human TRH
Thyrotropin-releasing hormone(TRH)
Thyrotropin-releasing hormone(TRH): Functions
- stimulates the secretion of thyroid-stimulating hormone from the pituitary
- affects the secretion of prolactin from the pituitary
- luteinizing hormone-releasing hormone (LHRH)
- peptide chain of 10 amino acids
- synthesis and release of: luteinizing hormone (LH) , follicle-stimulating hormone (FSH)
- GNRH1 gene for the GnRH precursor is located on chromosome 8
- the linear decapeptide end-product is synthesized from a 92-amino acid preprohormone in the preoptic anterior hypothalamus
- secreted in the hypophysial portal bloodstream at the median eminence
- portal blood carries the GnRH to the pituitary gland
Gonadotropin-releasing hormone (GnRH)
- single chain of 41 amino acids
- Stimulates synthesis and secretion of corticotropin (adrenocorticotrophic hormone; ACTH) in the pituitary gland
- Regulated by: Cortisol, vasopressin
- often produced in response to biological stress
- the hormone also has anti-inflammatory actions in its own right, through activation of macrophage (melanocortin) MC3 receptors
- Used as a test to assess adrenal function
- Increased ACTH adrenal insufficiency
Corticotropin-releasing hormone (CRH)
(Corticotropin-releasing hormone (CRH))
-principal effects are increased production and release of cortisol by the cortex of the adrenal gland:
- increase blood sugar through gluconeogenesis
- suppress the immune system
- aid in the metabolism of fat, protein, and carbohydrates
- decreases bone formation
Corticotropin-releasing hormone (CRH)
Excessive secretion of CRH leads to an increase in the size and number of corticotrophs
- pituitary tumor
- Cushing’s syndrome
deficiency of CRH-producing cells
- adrenocortical deficiency
- Somatoliberin, somatocrinin
- peptide with 40-44 amino acid residues
- Produced n the arcuate nucleus
- Blocked by somatostatin
- stimulated by stresses (physical exercise)
- Negative feedback control mediated largely through somatomedins (IGF)
- Isolated deficiency of GHRH may cause dwarfism
Growth hormone-releasing hormone (GHRH or GRH)
- a peptide of 14 amino acid residues
- Inhibits the release of growth hormone and thyroid-stimulating hormone (TSH, thyrotrophin) from the anterior pituitary
- Growth hormone release-inhibiting hormone (GHRIH), somatotropin release-inhibiting hormone (SRIH)
- refers to a number of polypeptides consisting of chains of 14 to 28 amino acids
somatostatin
- hypothetical human hormone or hormone releasing factor which regulates the circulating level of prolactin
- prolactin is the only currently known hormone for which almost exclusively negative regulating factors are known but few stimulating factors
- thyrotropin-releasing hormone, oxytocin, vasoactive intestinal peptide and estrogen
Prolactin Releasing factor (PRF)
secreted at several locations in the digestive system
- Delta cells in the pyloric antrum
- the duodenum
- pancreatic islets
suppresses the release of gastrointestinal hormones:
- Gastrin; Cholecystokinin (CCK); Secretin; Motilin; Vasoactive intestinal peptide (VIP); Gastric inhibitory polypeptide (GIP)
Potent inhibitor of many functions in the GI tract
- Stomach acid secretion
- Secretion of pancreatic enzymes
- Intestinal absorption
Somatostatin
- Dopamine and GAP (GnRH-associated peptide)
- The hypothalamic regulation of prolactin secretion from the pituitary is different from the hypothalamic regulation of other pituitary hormones in two respects:
1. the hypothalamus primarily inhibits rather than stimulates the release of prolactin from the pituitary
2. this major inhibiting factor is not a neuropeptide, but rather the neurotransmitter dopamine
Prolactin release-inhibiting hormones
- lies in a pocket of the sphenoid bone at the base of the brain (Selluaturcica)
- The optic chiasm is 5-10mm above this diaphragm
- Hypophysis; “master gland”
- roundish organ that lies immediately beneath the hypothalamus
- two distinctive parts:
anterior pituitary (adenohypophysis)
posterior pituitary (neurohypophysis)
Pituitary Gland
Pituitary Gland Secretes:
- thyroid-stimulating hormone (TSH, thyrotropin)
- adrenocorticotropic hormone (ACTH)
- luteinizing hormone (LH)
- follicle-stimulating hormone (FSH)
- Prolactin
- growth hormone
Hormone: Anterior Pituitary vs Posterior Pituitary
Anterior Pituitary
- Growth Hormone (Liver, adipose tissue)
- Thyroid-stimulating hormone (Thyroid Gland)
- Adrenocorticotropic horond (Adrenal gland(cortex))
- Prolactin (Mammary Gland)
- Luteinizing Hormone (Ovary and Testis)
- Follicle-stimulating Hormone (Ovary and Testis)
Posterior Pituitary
- Antidiuretic Hormone (Kidney)
- Oxytocin (Ovary and Testis)
- protein hormone of about 191 amino acids and two intramolecular disulfide bridges
- Secreted by somatotrophs and is the most abundant pituitary hormone
- The main effect of growth hormone (and its analogues) is to stimulate normal growth and/ it affects many tissues
- Plasma concentrations low during the daytme (
Somatotropin
Growth Hormone: Two distinct types of effects
- hormone binding its receptor on target cells (direct)
2. mediated primarily by a insulin-like growth factor-1 (IGF-1) (indirect)
Metabolic Effects of Growth hormone
Protein metabolism - increased amino acid uptake, increased protein synthesis and decreased oxidation of proteins
Fat metabolism - triglyceride breakdown and oxidation in adipocytes.
Carbohydrate metabolism - “anti-insulin activity”
Mineral metabolism- positive calcium, magnesium and phosphate balance
- Promote of Na+, K+ and Cl- retention
Control of Growth Hormone Secretion
Growth hormone-releasing hormone (GHRH)
- Hypothalamic peptide
- Stimulatory
Somatostatin (SS)
- Hypothalamus, stomach
- inhibitory
Ghrelin
- stomach
- stimulatory
Growth Hormone: Disease States
Dwarfism - deficiency in growth hormone or receptor defects
Gigantism - excessive growth hormone secretion that begins in young children or adolescents
usually resulting from a tumor of somatotropes
Acromegaly - excessive secretion of growth hormone in adults
- Thyrotropin
- secreted from cells in the anterior pituitary called thyrotrophs
- glycoprotein hormone composed of two subunits
alpha subunit present also in FSH and LH - Effects:
*increases all phases of T3 and T4 biosynthesis
*increases in the synthesis of proteins, phospholipids, and nucleic acids and in the size of number of thyroid cells
*thyroid-releasing hormone most important controller
Thyroid Stimulating Hormone
- corticotropin.
- stimulates the adrenal cortex by enhancing the conversion of cholesterol to pregnenolone
- stimulates secretion of glucocorticoids such as cortisol from the adrenal crtex
- little control over secretion of aldosterone
- secreted in response to many types of stress
- inhibited by glucocorticoids —> Feedback inhibition
- Within the pituitary gland, ACTH is produced in a process that also generates several other hormones
- proopiomelanocortin (POMC) cleaved into: ACTH; Lipotropin; Beta-endorphin; Met-enkephalin; Melanocyte-stimulating hormone (MSH)
Adrenocorticotropic Hormone
- single-chain protein hormone closely related to growth hormone
- secreted by so-called lactotrophs in the anterior pituitary
- 199 amino acids
- three intramolecular disulfide bridges
Prolactin (PRL)
Control of Prolactin Secretion
- Hypothalamus suppresses prolactin secretion from the pituitary
- Dopamine - Major inhibiting factor (D2 receptors)
- Postively regulated by thyroid-releasing hormone, gonadotropin-releasing hormone and vasoactive intestinal polypeptide
- stimulates secretion of sex steroids from the gonads
In the testes - stimulates the synthesis and secretion of testosterone
In the ovary - secretion of testosterone, which is converted into estrogen by adjacent granulosa cells. - required for continued development and function of corpora lutea (Induces luteinization of ovarian follicles)
Luteinizing Hormone
- stimulates the maturation of ovarian follicles
- critical for sperm production
- supports the function of Sertoli cells
Follicle-Stimulating Hormone
- Oxytocin and vasopressin
- Small peptides (8-9 amino acids)
- Synthesized in the hypothalamus
- Stored in the pituitary
- Release is NOT under control of hypothalamus releasing hormones
Posterior Pituitary Hormones
- a nine amino acid peptide
- key player in control of body water and solute concentrations
- conserve body water by reducing the output of urine
Antidiuretic Hormone (Arginine Vasopressin)
Effects of Antidiuretic Hormone
- stimulates contraction of the muscles of the capillaries and arterioles, raising blood pressure
- promotes contraction of the intestinal musculature , increasing peristalsis
- stimulates water reabsorbtion by stimulating insertion of “water channels” or aquaporins into the membranes of kidney tubules
Antidiuretic hormone receptors
- V1, V2 and V3
- V2 receptors, which are coupled to adenylate cyclase, mediate its main physiological actions in the kidney
- V1 and V3 receptors are coupled to the phospholipase C/inositol trisphosphate system
Control of Antidiuretic Hormone Secretion
- Plasma osmolarity
2. decreases in blood pressure and volume
Physiologic Effects (ADH)
- Released in response to ↓ Blood pressure
- Acts to maintain blood osmolality and volume
* Increases water reabsorption in the collecting ducts of the kindey - Binds to V2 receptors in the kidney
- Binds to V1 receptors in the vascular smooth muscle (vasoconstriction)
- stimulates blood platelet aggregation and mobilisation of coagulation factors
- In the CNS, ADH acts as a neuromodulator and neurotransmitter
- When released into the pituitary ‘portal circulation’, it promotes the release of ACTH from the anterior pituitary by an action on V3 receptors
- characterized by excessive thirst and excretion of large amounts of severely dilute urine
2 Causes:
Hypothalamic (“central”) diabetes insipidus
Nephrogenic diabetes insipidus
Diabetes Insipidus
- nine amino acid peptide
- synthesized in hypothalamic neurons
- transported down axons of the posterior pituitary for secretion into blood
Oxytocin
Oxytocin Function
- Oxytocin Causes Contraction of the Pregnant Uterus
- Oxytocin Aids in Milk Ejection by the Breasts
* milk letdown or milk ejection
- Takes part in the regulation of cellular responses to cytokines and growth factors
- Cytokines are a group of proteinaceous signalling compounds that, like hormones and neurotransmitters, are used extensively for inter-cell communication
JAK-STAT signaling pathway
- are therapeutically useful agents for the treatment of a variety of inflammatory and immune diseases
- Their anti-inflammatory and immunomodulatory actions are explained in part by the inhibition of NF- κB and its subsequent actions
Glucocorticoid hormones
- is a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription
- The sequence is most commonly a pair of inverted repeats separated by three nucleotides, which also indicates that the receptor binds as a dimer
- A gene may have many different response elements, allowing complex control to be exerted over the level and rate of transcription
Hormone Response Element (HRE)
- An acetyltransferase enzyme which regulates genes by activating transcription
- They are nuclear receptor coregulators
CBP and its close relative, p300, interact directly or indirectly with a number of signaling molecules - Several other families of coactivator molecules have been described (ex. P160)
- The exact role of these coactivators is presently under intensive investigation
CREB-binding protein, CBP
