Thyroid gland is located at the base of the neck and wraps around the trachea below the cricoid cartilage. The two lobes are connected by a isthmus. A pyramidal lobe, is a remnant of embryonic thyroglossal duct, is sometimes present. The thyroid gland is about 20g but can grow if patients have goiters. The blood supply comes from the inferior and superior thyroid arteries that come from the external carotid and subclavian arteries. Venous drainage is through the paired superior, middle, and inferior thyroid veins into the internal jugular and innominate veins. It has a rich lymphatic system that play an important role in delivery of hormone to the general circulation. It also has abundant supply of sympathetic and parasympathetic nerves.
Vitamin notes taken in class.
Vitamins-organic nutrients body needs in small amounts only. In terms of mg sometimes micro grams. You don’t need vitamins in grams except vitamin C. 1G only. Usually vitamins are not synthesized in the body vitamin D and niacin are the exception. They must be provided in diet. Exception is vitamin D, from cholesterol. You need sunlight for the activation of Vitamin D. Vitamins don’t give you calories and can’t be substituted by carbs/proteins/fats. You can’t live off multi-vitamins.
Fat-soluble ADEK. Water soluble vitamins are vitamin C and B complexes. The first difference between fat-soluble and non-fat soluble vitamins are: Fat soluble are non-polar or hydrophilic vitamins. Water soluble vitamins are polar. The second difference is fat soluble requires fat in your diet, you can’t absorb fat soluble vitamins without fats. These are stored in liver and adipose. For B-complex you don’t store EXCEPT for vitamin B12. Since you can store fat-soluble vitamins you can get toxicity è liver toxicity. But because fat-soluble are stored you are less prone to deficiency for ADEK since you have storage. You require lipoproteins for fat-soluble. Excreted via urine for water-soluble. Fat-soluble is usually excreted in bile.
Most pathways require vitamins.
Vitamin B1 - Thiamine
Is composed of methylated pyrimidine ring with thiazole ring. TPP is most important coenzyme form. Marjory of function is carb metabolism. Required metabolism is 1:1 thiamine and carbohydrate. 1-1.5mg of VitB1. Add K ferricyanide è thiochrome è spectrophotometer è concentration of vitamin B1, quantitative way of measuring thiamine.
Energy releasing vitamin. First coenzyme of carb metabolism is TPP during pyruvate dehydrogenase. Without TPP your glucose can’t go through oxidative phosphorylation. You need to produce 40ATP but you make 10ATP. 1st manifestation You get severe muscle weakness. Weakness also affect cardiac muscles. You can die from Vitamin B1 deficiency. You get beriberi. You get edema in beriberi. Pyruvate will become lactate è lactic acidosis will occur.
Acetyl coA is from pyruvate è CAC and can also come from fats è beta oxidation, and catabolism of amino acids. You can get a shit load of ATP as long as you have acetyl CoA. But even if you have acetyl coA you can’t go through CAC because alphaKG needs TPP also. Any vitamin involved in a pathway that produces ATP è energy releasing vitamin.
Introconversion of sugars. Transketolase and transaldolase. Transketolase transfers 2 carbons. Transaldolase tranfers 3 carbons. Transketolase active only with thiamine. Review PPP. If you don’t have thiamine, transketolase is inactive. Ribose and xyulose will accumulate. Accumulation of pentoses è pentocemia. The 3rd manifestation of thiamine deficiency è leads to pentosuria. Measure Transketolase activity to get quantitative assay to determine status of vitamin B1.
Metabolism of nerve tissues. Thiamine triphosphate, neural vitamin. With deficiency of VitB1 you’ll have neurological manifestation 4th manifestation. Initially it is tingling sensation of your fingers and toes, manifestation. Eventually numbness è you’ll have paralysis.
If your main source of energy is rice, polished and unpolished rice. Unpolished rice is made in remote area, hand-pounding. During milling process it removes the outer covering of rice è where most of VB1 is located. You decrease your intake of vitB1 if you eat unpolished rice. DARAK. DARAK eaten by pigs, and you eat pigs. In polished rice, the outer layer of rice in in-tact. So you’ll get 80% higher Vitamin B1 (thiamine). Normally, unless the rice is from dirty place, you wash it 2 times, before you cook it. You remove 5-10% of VitaminB1 washing it. If you don’t use rice cooker, and you can’t get the amount of water right you dump out water è lose another 5% of VitaminB1. If you just rely on rice you’ll get vitamin B1 deficiency. There is a way DARAK is converted into flour, the nutrition center of Philippines, prepared DARAK so that it become flour like consistency so you can bake it now. You can make it biscuits. Probably you tasted it already usually before the biscuits are used in seminars for snacks è high in VB1.
Ingestion of foods containing anti-thiamine factors. Raw fish, sushi, sahimi, raw oysters, raw clams. Rich in thiaminase is an anti-thiamine factor because it destroys thiamine. 3rd trimester in pregnancy and lactation you’ll be thiamine deficient so you’ll need to double your VB1. 4th cause of thiamine deficiency is hard physical labor. If you see them, they eat rice. They don’t eat much of anything but rice, and they can’t buy multi-vitamins because they are poor. They are prone to thiamine deficiency. Caloric intake, the higher caloric intake the higher vitB1 requirement. High in fat intake, you only require 1 TPP. In carbs 2 TPP needed. In pregnant and lactation, and activity will increase intake of VB1. Age refers to retirement 60 up, supposedly you are not working anymore, so you expect their activity goes down and VB1 also decreases. Less activity less intake of food. As you grow old the capacity to absorb goes less. At our age, if we eat, we can absorb 90%. If you get old you’ll only absorb 30%. So when you grow old you requirement goes up and there is a special type of multi-vitamins for old people, the concentrated type è centrum silver. The concentration is double in concentration. You take centrum silver, but the price is also doubled.
All diseases that increase BMR also increase VitB1. Chronic peripheral neuritis is the normal beriberi. Acute pernicious beriberi, shoshin beriberi, is heart failure and metabolic abnormalities predominate without peripheral neuritis. Whenever you see fulminating you’ll die 2 weeks time. Wernicke-Korsakoff syndrome is in alcoholics because alcohol prevents the absorption of thiamine. Mental confusion, ataxia, and opthalmoplegia- loss of eye coordination.
The adult type of beriberi 3 types. 1stDry typeè neurologic symptoms. The 2nd type is cardiac type edema. And there is 3rd type mixed.
For the infantile is phonic type- no sound because of pharyngeal paralysis- a baby that doesn’t cry. The cry is like a cat. Babies need to cry to develop their lungs è it expands. When they’re sleeping don’t wake them up, you need to examine them first, listen to heart lungs, then examine everything outside, then you wake them up and make them cry, to look inside their mouths. That’s how to examine a baby. The second type the pseudomeningitic type is convulsions. These convulsions occur without fever. It’s easy to diagnose if they have a fever because convulsions are caused by the fever. Without a fever than it’s harder to diagnose because so many genetic defects have convulsions. How do you rule out? You cant because there’s too many. You’ll rarely think its beriberi unless the mother is malnourished. But if the mom is fine then you wont think it’s beriberi. The third type (cardialgic) is cyanosis manifestation- the baby is blue. They have cardialgic type of beriberi. The reason why they can’t stand is because they have severe weakness and have big feet because of edema. Its called pitting edema.
Vitamin B2- (VitB2 / Vit G / Lactoflavin)
lactoglobin/riboflavin (FAD) the best source is milk. 1 quart of milk a day you get your days requirements of vitaminB2. Required daily intake (RDA) = 1.2-1.7 adult. 2.0-2.5 in pregnant/lactating women
Energy releasing vitamin. The most important function is hydrogen transfer reactions redox reactions. The flavin ring is where the hydrogen attaches and detaches the active part of riboflavin that is involved in redox reactions. Part of the krebs/CAC: succinate è fumarate. It is also an energy releasing vitamin. Glycerophosphate to DHAP gluconeogenesis. Just like thiamine it is also part of pyruvate DH and alpha-ketogluterate DH complexes (so glycolysis and CAC). It’s also required in the electron transport chain(FAD è FADH) to carry electrons.
Uric acid synthesis. Aside form that, it’s needed in the synthesis of uric acid: (1)conversion of hypxanthine èxanthine (2) hypoxanthine è uric acid. Both reactions use xanthine oxidase, so xanthine oxidase needs VitB2 as a coenzyme.
Glutathione. Glutathione also requires FAD, reduces glutathione to keep it active. You assay glutathinone reductase to access vitamin b2. If it is active then you have active vitB2.
Manifestations. Are mostly in the mouth. Cheilosis è angular stomatitis, painful cuts in the mouth. Also you have magenta tongue secondary to glossitis è inflammation of tongue. Corneal vascularization è you get reddish eyes. This is different from acute conjunctivitis because it doesn’t have pain. You’ll develop seborrheic dermatitis è scaly dermatitis especially around nasolabial folds and scrotal areas. And photophobia secondary to vascularization.
Niacin- Vitamin B3.
Energy releasing vitamin. Like riboflavin. It acts in redox reactions. Examples, of a reaction is in the krebs cycle which involves isocitrate, malate, and alphaKG. Niacin is energy releasing. Aside from the 3 enzymes of CAC you also need NAD+ to convert lactate to pyruvate during gluconeogenesis. Aerobic glycolysis, the reverse is gluconeogenesis. You need to know all the pathways where vitamins are involved. 2nd reaction krebs/ketogenesis (look at book).
Synthesis.You can synthesize Niacin from tryptophan. You need Vitamin B6 and vitamin B2 to convert tryptophan to niacin. If you don’t have B6 and B2 then you’ll end up with niacin deficiency. Both manifest with pellagra. The 3 Ds: dermatitis, dementia, diarrhea.
Specifically if B6 is deficient, hydroxyl (??) è xanthoric acid (???) only occurs if VitaminB6 is deficient. Do a tryptophan load test. If xanthorenic(???) increases than the patient is deficient in vitamin B6. Take note that B6 needed to convert tryptophan to serotonin. The first step in catabolism is called tryptophan tyrolase è hartnup disease, where you can’t convert tryptophan to niacin. It manifests the 3Ds.
Dermatitis manifests and is located in the areas of the skin that is exposed to the sun. Full-blown dermatitis, your skin is black to dark-brown. Neck-lesions is called casal’s necklace. Lesions on the arms and legs is called gloves and stocking lesions. The lesions look lace-like in appearance. Initially they’re pink/red in color and its called maldelerosa (its Spanish “bad” “red/pink”). Dogs can also develop this and they’ll get a black tongue. There will be sloughing of off mouth mucosa. Tongue is always out because it stings and so it turns black. Dogs eventually will die if untreated because they won’t eat. Diseases of pellagra – Carcinoid syndrome because of overproduction of serotonin è divert pathways away from NAD synthesis. Manifestations of pellagra but the face is spared from lesions. Treat with high dose of niacin. Don’t give a high dose of niacin to normal people or else they’ll get a severe allergic reaction (because it releases histamine). If you know they get severe allergic reactions then just give the usual dose of niacin.
Vitamin B6- (Pyrodoxine / pyridoxal / pyrioxamine)
aka amino acid metabolism vitamin because it is related to protein metabolism. Requirement is directly proportional to protein intake. Just like how vitB1 : carbohydrate. Vitamin is also called Vitamin H (Dr. Harris discovered it). Ademin- because it’s anti-dermatitis vitamin.
Manifestations. To produce GABA (natural tranquilizer) you need PLP (pyridoxal phosphate) most active form of B6. If you are deficient in vitamin B6 then you’ll decrease GABA and then you’ll get convulsive seizures. Pellagra-like symptoms manifests because you have no tryptophan being converted to niacin. If you are deficient in B6 you’ll can’t convert tryptophan è serotonin (which is used as a neurotransmitter and for normal GIT contraction). You’ll manifest with camps, vomiting, and diarrhea. PLP is also the carrier for transamination. You also can’t produce heme and will present with hypochromic (pale) microcytic anemia. When you’re deficient in vitB6 you’ll have an accumulation of homocysteine because it is related to the catabolism of methionine. Normally SAM is converted to homocystein è cysteine. When homocystein accumulates èhyper-homocystemia. This leads to hypertension because homocystein in blood causes injuries to the blood vessel walls. Once you have damaged walls, than cholesterol will cling to the walls and atherosclerosis will occur.
The treatment is to lower the level of homocystein. You need VitaminB6 to decrease the level of homocysteine because it hastens the conversion of homocysteine è cysteine. High dosage of Vitamin B6 usually doesn’t work because patients with hyperhomocystemia are also deficient in enzyme cystathionine synthase (inborn error). If the enzyme is deficient than giving high dose of VitB6 won’t work. How do you lower levels of homocysteine then? You’ll want to convert homocysteine back to methionine with the use of vitB9 (folic acid) and VitB12.
Energy releasing vitamin. VitB6 is considered energy releasing vitamin because it derives its energy from amino acids.
More manifestations… Anemia is present if deficient. Oxalate stones will also form because glyoxalate is usually converted to glycine in the presence of VitB6. Without VitB6 glyoxalate will eventually turn into oxalate stones. You can also get oxalate stones with large doses of vitamin C. It gives rats abnormal pigmentation. Assay transaminases/aminotransferases to see if a person if VitaminB6 deficient. If the transaminase is active, than you have normal vitB6 levels.
Panthothenic Acid or “the everywhere vitamin”. Usually people aren’t deficient in this because God put this vitamin everywhere. The most important component is coenzymeA. Mostly all the pathways need coA. If you are deficient in panthothenic acid then you’ll die because you can’t go though pathways è no energy. There are still instances where you can develop deficiencies because when you eat food that inhibit panthothenic acid then you’ll be deficient in this. It is found in royal jelly, derived form beehive’s honey.
Energy releasing vitamin. There are 3 forms: succinylcoA, acyl carrier protein, and acetylCoA. Krebs cycle’s first reaction in the formation of citrate needs pantothenic acid. No krebs cycle without pantothenic acid. Most common manifestation is fatigability because you’ll have no energy to do anything since you have no energy. This is different from laziness. Most people our age who are tired aren’t diagnosed with pantothenic acid deficiency if they say they are tired all the time. First rule out any heart problems, then lungs, then kidneys. These organs is responsible keeping us active. If all the tests come back normal then you’ll diagnose with pantothenic acid deficiency. Start with 25mg or if the person is larger, 50mg. You can ingest pantothenic acid if you’re always tired.
Steroid synthesis. This also serves as precursors of steroid hormones. So if you are deficient in pantothenic acid then your adrenals won’t produce hormones è atrophy of the organ. No hormones means your metabolism will also be affected. No activity will lead to depression.
Depression presents itself usually during puberty (if the kid doesn’t know what’s going on w/ his or her body) and graduation (because of having no job and money). Parents think medical students will be rich after they graduate but in reality they only make 8-10k(residency in private hospitals) or 18-20k(in public hospitals). There is a wrong notion you make big bucks initially; it takes about 10 years for you to roll in dough. An FEU student finished their residency abroad and came back to Philippines. Doctora asked “what’s your plan now? Are you going to practice here or abroad?” he answered “I don’t know”. Then doctora thought “then why did you do residency in the first place?”. Then doctora said “why don’t you teach biochem with us?” the kid said, “I don’t even know how I passed biochemistry”. Then the kid went back to his province Batangas, sat under a coconut tree and pulled the trigger in his temple. Another FEU student who was a top-notcher commit suicide. (Great school huh…)so the bottom line is to make sure you’re not deficient in pantothenic acid or else you’ll commit suicide, and most likely die.
If you are deficient in pantothenic acid, you will be deficient in succinylCoA and you’ll produce less heme. You’ll present with anemia. You’ll also be deficient in ACP- involved with extramitochondrial lipogenesis and protein and lipid metabolism.
VitaminB12- is found in egg yolk but in the egg whites there is avadin. Avadin is an antagonist of VitB12. It also is responsible for hair loss and early hair going gray. VitB12 is major component of amphibolic reactions. Its involved in CPS- urea cycle and it forms C6 in the synthesis of purines (comes from CO2). It causes depression and hallucinations when you are deficient in it. Rats have spectacle appearance, where they lose hair around their eyes and look like they have white eye glasses.
Folic acid Vitamin B9 is also called THF. The active part of THF is N-5 and N-10. It carries 1 C units usually methyl, formyl groups ect. Either 1C groups attached to the 5-N è N5 methyl folic acid – most abundant. If formyl on N10, called N-10-formyl folic acid. Activation 2 steps of reduction (1) NADPH + folate reductase + Vit C keep it reduced (2) another THF acid THFA. A group of drugs are called folic acid antagonists. They inhibit folate reductatse. It prevents purine and pyrimidine synthesis in the steps where THF is involved. You need them for DNA synthesis, growth, and maturation. The drugs prevent THF activation and is used in cancer patients. It is a double-blade drug because it also kills normal cells.
If you apply THF to RBC è they’re large at first but then when they mature they become smaller. You need DNA for maturation. A deficiency in folic acid è RBC will remain big and immature è megaloblastic/macrocytic anemia. VitB12 also produces megaloblastic anemia but with the addition of neurological symptoms. Folic acid does NOT have neurological symptoms associated with it.
Another function is its relation to histidine. The catabolism of histidine è uroconic acid è FIGLU è glutamic acid. If deficient in folic acid, then FIGLU wont become glutamic acid èit will instead be excreted in the urine in great amounts. FIGLU excretion/ histidine load test. Most significant job of folic acid is its participation in purine and pyrimidine synthesis è NO DNA. Stoeratitis (???) and magenta tongue will also present. Rats acrotencia – abnormal pigmentation of hair in mice, looks like they have “highlights”. There are drugs that interfere with folic acid, like anti-convulsion drugs, and contraceptive drugs. You need to give a higherER dose of folic acid if the patient is already deficient in folic acid. For manifestations pan cytopenica means all WBC/RBC/platelets are low because no DNA. There is also growth failure.
B12-cbalamine because it has cobalt in the center and pernicious anemia. Megaloblastic anemia (pernicious anemia) AND neurological manifestations occur if you’re deficient. Extrinsic factor castle (another name) because it needs intrinsic factor for it to be absorbed (made in stomach). Total gastrosectomy means all of your stomach is removed and a plastic bag replaces it. You’ll need to inject VitB12 forever because you’ll be forever deficient in intrinsic factor.
All the B12 is stored in the liver. So you only have to get injections once a month, intramuscularly DEEP because of it’s viscosity. The needle needs to be 1.5 inches long. It is a vitamin structure that resembles heme with 4 pyrrole rings except in the center, instead of iron, it is cobalt. Whatever you attach to cobalt is what VitB12 is called. Example, methyl cobalt is what VitB12 is called if methyl group is attached to it (it’s the most common). 5’dexoy ..(???) gringard reagent (review your organic chemistry). Corrin ring system.
Maturation of RBC. Pressure of B12 prevents trapping of folic acid in methyl form. Look at page 126 in lecture guide. Remove methyl so folic acid is free. It is needed for purine and pyrimidine synthesis è add B12 to remove. “prevention of the trapping”.
Biochemistry Vitamins (Part 2)
BeriBeri- which was not in class last time. Vitamin B1 deficiency, thiamine. They have edema è pitting edema. Opthalmoplegia- no coordination of eye movement. For VB2 deficiency, this is the stomatitis and angular stomatitis- inflammation of the tongue. It has secondary infection there is puss. You can’t just inject VB2 but also antibiotics for the infection. Opening of the mouth is limited. Glossitis- the tongue is hardened and sense of taste is gone, this is chronic sickness. Pellagra- black cassal’s necklace. For this particular tribe there is facial lesions, usually there isn’t lesions è high dose of niacin. The lesions are on hands and legs, so that’s pellagra. Biotin deficiency è alopecia or loss of hair. And for the rats there’s a spectacle eye appearance, where the hair around the eyes are lost so it looks like they have white eye glasses. Those were the pictures that were not here last time. Last water soluble vitamin, vitamin C.
Among all the vitamins, vitamin C is the most easily destroyed. Even at room temperature, it can destroy vitamin C. Day by day fruits’ and veggies’ vitamin C goes down so put it inside the refrigerator. Uronic acid pathway includes vitamins C è ascorbic acid from glucose. We don’t do that because we don’t have the enzyme gulonolactone oxidase. So we need vitamin C in the diet everyday. The extra vitamin C we excrete, so tomorrow we need to take it again. We can’t store it.
Oxalic acid comes out in crystals. High vitamin C creates oxalic stones formation è cystals. Vitamin B6 deficiency also causes oxalic acid formation. You’re not going to form oxalate stones (from high vitC) as long as you drink plenty of water because when you urinate there will be a lot of volume so the crystals won’t aggregate.
Collagen synthesis. Vitamin C function is synthesis of collagen. You have discussed this before in conference. Hydroxylation of hydroxyproline and hydroxylysine. Why is it important to form these? What is the primary structure of collagen? (Gly-x-y)n- x and y are amino acids. Vitamin C deficiency leads to no hyroxyproline and lysine è form abnormal collagen, collagen not as strong as it should be. Collagen is the most abundant protein in the body, including blood vessel wall. Your blood vessels can rupture è spontaneous bleeding and hemorrhages.
Ferric, ferrous role. Another important is ferric è ferrous Fe2+. Foods you eat are usually ferric. You need vitamin C so you can absorb iron. You can develop iron deficiency if you don’t have vitamin C. So if you go to stores, you’ll see that iron supplements will have vitamin C with it. The presence of the vitamin C ensures absorption of the iron. Also Dra. Santos mentioned before, if folic acid can’t be converted to the active form è megaloblastic type of anemia.
Cholesterol excretion. The role of vitamin C on cholesterol. Only way to excrete cholesterol is to react it with vitamin C so cholesterol doesn’t deposit on blood vessel wall. If you go to a party you’ll eat high fat foods because there’s no such thing as a vegetarian party è so make sure you take high dosage of vitamin C when you eat plenty of fatty foods at a party. Take vitamin C 1000mg before (the party), and serine 500mg each to promote conversion of cholesterol to bile acid so it won’t accumulate on blood vessel wall, and you will prevent atherosclerosis.
Antioxidant role.It is also an anti-cancer vitamin (ACE- vitamins that are anti-cancer). Prevents nitrosamines. Colored foods, like hot dog, tapa, tosino, and foods with preservatives è all cancer producing substances. To prevent this 1000mg of vitamin C. It makes immune system strong especially if there is an epidemic. That’s why when there was SARS epidemic they ran out of vitamin C, because they wanted to make people’s immune system stronger.
Bones. It also is related to bone strength since the bone matrix needs vitamin C. You need a higher concentration of vitamin C in your diet. If you read a book about philippinos only 100mg of vitamin C. But if you look at all the function of vit C in your body 100mg isn’t enough. Your diet is usually high in carcinogenic substances, take 1000mg of vitamin C. The best source of vitamin C is guapple, (20 pieces of calamanci are needed for you to get 1000mg, so it’s not a good source of vitamin C. Dra. Santos: “there is a banana apple è I heard it when I was on tour in Hawaii the tourist guide and bus driver said to look to the left, where the mountain of Jurassic Park was shot. And the he said to look to the right where the beach scene was shot. Eat banana apple è ‘why is banana apple circle’ asks doctora? Nipahut?? That was manned by a woman that worked as a farmer that was a filippino (so was the driver, was also Filipino but spoke Hawaiian). There were different people on the bus. So Dra was like ‘that is a lakatan’. Toron was being sold 5 dollars a piece = 200p. Dra. Said ‘you’re robbing me, that’s why you’re so rich’ so Dra. Santos thought of selling toron there also instead of being a doctor. The filippina gave Dra. Santos 2 torons because she was filippina and because she knew she was getting robbed by paying 5 dollars for toron.
Manifestations.So what are the effects of Vitamin C? Scurvy. Gums are red and bleeding and spongy. Falling of teeth but scurvy is more than that. Not healing cuts. Decreased ability to combat infections there are also skin changes. Its like vitamin A, your skin gets rough if you have vitamin C deficiency. There are spontaneous hemorrhages brought about the fragility of blood vessels. This is the reason why when you go to sleep you have hematoma when you wake up (IF you have vitC deficiency). This is especially true for women. During menstruation. What is a rosary? It’s filled with beads. It’s swelling of junctions of sternum and ribs. Under normal conditions it’s not prominent but vitC deficiency you’ll see it on chest. Scorbutic Rosary. Vitamin D- Rachitic rosaryè same thing as vitamin C deficiency. The usual manifestations: easy fatigability, and weak bones. Now this is Vitamin C deficiency, initially swollen and bleeding gums. Then you’ll have loosening of the teeth and then it will fall eventually. Then splinter hemorrhages, under your nail beds. You’ll have rough skin. Scorbutic Rosary Beads on the chest. Scurvy, your skin you’ll have sandpaper skin. So if you rub elbows with a friend they’ll get cuts because your skin is so rough (I think she is exaggerating here…MAYBE).
Fat soluble vitamins are stored so you can’t take large doses of this because its toxic to the liver.
VitaminA should not be given to pregnant women in high doses because it will cause abnormalities in fetus. The precursors are carotenes. The best is beta-carotenes because you’ll already get 2 mols of vitamin A, retinal retinol, and retinoic acid. The retinoic acid is least stored and least toxic. The conversion of beta-carotene takes place in the liver, small amounts in intestinal cells. For you to convert you’ll need thyroid hormone, zinc, insulin, and vitamin E to prevent destruction of vitamin A. Vitamin A is easily destroyed by oxidative reactions. Now take note that you need insulin. This is the reason why diabetics who lack insulin have dry skin. If your skin is dry, your tendency is to have itchy skin è patient scratches skin. If the fingernails are dirty and scratch è If this is infected, and you know that diabetics wounds take long to heal, can become infected and become gangrenous è cut of limb. It all started with a scratch. So if you’re a diabetic pat the itchiness, unless they want their limb cut off. If the patting doesn’t work then put a handkerchief on the skin.
Absorption. So what are the different factors that prevent absorption? The amount of fats you eat. Proteins and zinc, vitamin E. Now infections, usually viral, increases the catabolism of vitamin A. For children with rashes they need a high dose of vitamin A. Parasitic infections can also decrease absorption.
Vision. Different functions is vision. You need rhodopsin to see in the dark and rhodopsin is made up of opsin and 11-cis retina. So specific form of vitamin A is 11-cisretina. Deficiency of vitamin A, it’ll take a long time for your eyes to make rhodopsin è night blindness. That’s why night blindness is the earliest manifestation of vitamin A deficiency. Now this is reversible è with high dose of vitA.
Antioxidant. Another function is anti-infective vitamin è that makes it anti-cancer. Anti-infective vitamin and it is anti-cancer like vitamin C. It maintains normal lining of the epithelial lining è smooth and moist. It is said that if the epithelial lining is smooth and most it prevents entry of microorganisms. So this makes in anti-infective. It is also a barrier for carcinogenic agent è anti-cancer agents. If the lining dries up, you get cracks and opening. You compare that to a leaf. If you crumple it, in tact is the leaf. If you get a dry leaf, it will crumble into pieces, like the epithelial lining if you’re deficient in vitA. Then carcinogenic agents enter and you die from cancer. VitaminA is also maintains the smoothness of the skin. You get toad skin if you are deficient in vitamin A. The frog we eat isn’t rough. When you eat it its like eating chicken.
Other functions and more anti-oxidants. Another important function of vitamin A is its roll in growth of chondroitin sulfates. Its role is in males only. Dryness of epithelial in males è loss of spermatogenesis. Males will become sterile. You also need vitamin A for bones and teeth. For normal cell differentiation, it’s related in anti-cancer. No vitamin A it will lead to proliferative division of cell è cancer. Immune system gets stronger with vitamin A. Without it you’ll get more infections.
Vision, Filipino diets, other things that get fucked up. You need it in formation of rhodopsin so you can see in the dark. If vitamin A is deficient, earliest sign is nicteophia/night blindness. Then dryness of eyes è conjunctiva è serosis conjunctiva. Then you’ll develop foam like spots when you have serosis conjunctiva, higher on the lateral portion of the eye. Usually this doesn’t impair vision as long as it stays in the lateral portion of the eye, unless it coverers the eye. Give high dose of vitamin A. When the eye dries up è corneal ulcers è infected è pus formation in corneaè becomes soft jelly-like mass because of puss called it Keratomalacia . If it gets soft its easily opened è then all the shit in your eye comes out è you’ll become blinds. Usually this is what squatters suffer from. This is why they’re sometimes blind. You’ll see the scar of the rupture. Why are Filipinos prone to vitA even if they eat veggies? It’s more secondary to protein deficiency. Because you need proteins to transport vitamin A for absorption. If you look in Filipino diet, high in carbs, low in fats and proteins. So you’re low in protein to transport vitamin A.
The drying effect could be in epithelial cells so it’s easier for you to develop infections. So you can get respiratory infections. If kidney dries up è kidney stones. If glands dry up è blacks in glands. If it’s black then the secretions can’t go to target organ. Pancreas is connected to duodenum to pancreatic duct. If no pancreatic duct no lumen because they stick together so no pancreatic enzymes/digestive enzymes è no digestion è no absorption èmalnourished. Hormones are also produced in pancreas insulin/glucagon/ect. Bilot’s spots è blocks entire eye so you wont be see, but it can be reversed by giving vitamin A. What is permanent is if your cornea is affected. The cornea with ulceration with pus è opens è contents go out. (Grossss.) It will cause blindness, because nothing is in your eye. (duh Lol.) The only treatment for that is eye transplant.
For vitamin D.
It can be from veggies, but usually comes from cholesterol. You need to be exposed to sun. It’s called the sunshine vitamins. If you can’t have exposure to sunlight then you can’t activate it. Cholecaliferol è liver- 1 hydroxylation = 24-hyroxycaliferol, storage form of vitD in liver è kidneys its hyroxylated again 1,25 dihydroxycholecalciferol. Calcitrol. This is the one that performs vitamin D in body. The most important is absorption of calcium and phosphorous è bones and teeth strong. Bones and teeth will be weak w/o vitamin D. how does it maintain the calcium levels? It is used to increase absorption, reduces excretion of calcium, and mobilizes bone minerals. This is to maintain calcium serum level. If low calcium then withdraw bone calcium. This is called bone demineralization è bones will have holes, like a piece of wood with holes in it. So if someone bumps you you’ll die because your bones will all break. Plus if your serum Ca2+ goes down you’ll develop tetany. As much as possible they’ll withdraw all calcium. Uncontrollable spasms of muscles. Sometimes you experience that then your face twitches. Sometimes its not tetany its just fatigue of muscles. Laryngeal spasms è no voice. Most dreaded is cardiac muscles è then it’ll stop suddenly, cardiac standstill è death. No joke. Your body doesn’t wan that to happen. By the way, what’s the difference of tetany and tetanus? Tetanus is an infection by a deadly bacteria Clostridium tetani.
“During the years where we have oral revalida(???) You are lucky, one against 3 faculties. They can ask anything under the sun. So that’s a very traumatic experience, students shit themselves. So they took it out. Then the student says tetany for women tetanus for men. He turned out to be an idiot. He repeated med school.” (yet another great kwento)
Rickets in children. Osteomalasia in adults. The bones remain soft and pliable for children rickets. A form of bone deformation is a manifestation of rickets è bowleg and knocked-knees. Swelling of Rachitic Rosary è same shit as vitamin C. When you palpate you need to feel it, and its soft, then that’s vitamin D deficiency. If it vitamin C then there is angulation, a sharpness. So smooth for vitamin D. “there is contraction of peliv bones, you saw it in anatomy??” (Really. I didn’t see anything.) The hole is for delivery. If no hole then no delivery of baby. C-section. With vitamin D deficiency fontanlles are open even after a year. Baby’s teeth wont grow. Harrison’s growth depression under the lower border of thorax è advanced rickets, a spongebob head (says colleague Andrei) è the head is square.
Osteomalasia means easily fracture of the bones because there are holes in the bones è can lead to tetany because no more Ca2+.
Rejuvenating vitamin. Precursors are tocopherols and best is alpha tocopherol?? The best role is anti-oxidant. Anti aging because of its anti-oxidant. Intake of fats determines / poly unsaturated fatty acids. If you eat a lot of fats 20-25% more of developing cancer because if fats undergo oxidative destruction è fatty acid peroxides è toxic already è another oxidative destruction è radicals è carcinogenic. Then more fats you eat, the more radicals you produce è cancer. Vitamin E prevents the radical formation. So if you eat a lot of fats eat a shit tone of vitamin E. Carinogenic agents you’re exposed to comes from other foods like preservatives, and food coloring. So they’re all considered to be carcinogenic. Also in environment all the air pollutants. With all the exhaust coming form tricycles all of them are radicals so cover your nose and mouth, unless you want to get cancer.
Smoking causes cancer, it causes 35% of all types of cancer in your body. It doesn’t necessarily mean you’re the one smoking but second hand smoking is worse. I already told you about our lab technician because she married a smoker è 2years dedz. In FEU she married at 40, 2 years lung cancer. So if you wan to die within 2 years, marry a smoker, he’s going to kill you softly. So do not marry someone who smokes. What if you really love them? They say love lasts, it doesn’t. So don’t marry a guy who smokes because you will regret it since it is a 2-year death sentence.
Why is it rejuvenating? Anti-aging? If you’re going to study all the theories the most acceptable is the radical theory. The more exposed you are to radicals the faster you are in aging. It destroys more pathways è you age faster. The vitamin E is a radical scavenger- it converts radicals to not dangerous. Research is prostate cancer if high dose of vitamin E you get selenium it won’t cause cancer. There is already made Vitamin E with selenium 400mg vit E + 25mg of selenium. Vitamin E also inhibits shit in your respiratory tract. Patients were exposed to pollutants one w/ and w/o Vitamin e. those without vitamin E has lack of black spots in lung. Those with vitamin E have low black spots in lungs. This is because vit E inhibits damage. If you have low vitamin E the RBC easily hemolyse è hemolytic anemia. You need it to maintain muscle integrityè atrophy. Vitamin E and selenium prevents liver necrosis. It is useful in people who like to drink alcohol.
coming from plants. And one not coming from plants. I don’t know what they’re called. You inject vitamin K to prevent hemorrhagic effect in newborns. If you don’t know patient and you ask prenatal the usual answer is yes. If your not sure inject with vitamin K anyway. If the mother is deficient in vitamin K then the baby is also deficient. There will be continuous bleeding in the core, ear, nose. Spontaneous blood vessel rupture, and when it poops it is bloody, bloody shit (says colleague Andrei… amazing input btw). So to prevent all that shit just inject it with vitamin K meyadyon??. The main role is blood coagulation, factor 2,7,9,10. The specific reaction is called gama-carboxylation of glutamine acid residues. Gama-carboxylation is the coenzyme. All the synthesis that requires that needs vitamin K. this is also a component of co-enzyme Q. you also need vitamin K for bone-calcium binding proteins. This proteins also has gamma-carboxyl.
What are the conditions that cause vit K def. malabsorption, lack in diet, sterilization of antibiotics of gastro intestinal tract. Because bacteria produces vitamin K. For example, stone in bile duct è no bile è no bile salts è can’t absorb lipids è no vitamin K absorption or any of the fat-soluble vitamins ADEK. So you will show manifestations of all.
Toxicity of water soluble vitamins
Its not as often, and usually happens if you go on mega doses on long periods of time. Or if you’re allergic to vitamins
I know what you’re thinking “Dafuq?!”
Good luck my brehz.
Sit vis vobiscum.
How to use these notes: make sure you look at the diagrams in the biochemistry lecture guide. I know how most of you are allergic to textbooks, but it’s better if you look at the pathways in Harpers or Lippincott while you’re reading these notes. These notes are NOT trans. It’s from the books and hopefully it puts biochemistry in layman’s term. Make sure to cross reference with someone that did do trans though .Yup it’s work but hey, you’re the one that chose this profession (awoo-awoo).
Recap: Nucleotide Structure is made up of nitrogen base + pentosemonosaccharide (5 carbon sugar) + phosphate group. The bases are A/G/T/C/U. These bases can be modified through methylation / glycosylation /acetylation /or reduction. The reason why you want to modify the bases is so enzymes in your cell can “recognize” them to protect them from degradation. The phosphate groups on nucleotides are responsible for (-) charge and cause DNA/RNA to be called “nucleic acids”.
èSynthesis of Purine Nucleotides (adenine/guanine)
Purines are made in the liver. To create a purine ring you’re going to use a 5-phosphate ring (that’s already premade) and start adding carbons and nitrogens to it. The last sentence basically means your going to take a pentose (close your eyes and visualize a pentose) and your going to attach carbons and nitrogens to it until it looks like a purine. Your goal is to create inosine monophosphate (IMP). Why IMP?Because with IMP you can create ANY purine, meaning IMP can become either adenine or guanine. Here are the steps:
(1) Remember in FA metabolism you need to “activate” the FA chain before you can react it with anything. Same goes for purine synthesis. You need to “activate” the 5-phosphate ring using the enzyme PRPP synthetase. The product of PRPP synthetase is 5-phosphoribosyl-1-pyrophosphate (or simply PRPP). The enzyme name gives you a hint to what the product will be (PRPP syntetase = PRPP). Your body needs to regulate PRPP syntetase because you don’t want to make ridiculous amounts of purines. That would be inefficient and stupid. So to regulate it, your body uses negative feedback. PRPP is inhibited by its product: purines. It is activated by Pi.
(2) Committed step!! The committed step means memorize this upcoming enzyme. If you don’t learn anything from these notes, at least memorize this enzyme glutamine : phosphoribosylpyrophosphate aminotransferase (glutamine PRPP anminotransferase). It’s used for this rxn PRPP + glutamine = 5-phosphorylribosylamine. Glutamine PRPP aminotransferase is inhibited by it’s end products AMP and GMP (another negative feedback).
(3) So remember your goal is to make inosine monophosphate (IMP) the “parent” purine nucleotide. Your going to go through a bunch of reactions that you don’t need to know and use 3 ATP and 2 N^10-formyltetrahydrofolate (THF). That you need to know. Check the #of ATP used…I dunno if it’s right. Then boom. You have IMP.
(4) Once you have IMP you’d want to convert it to adenosine monophosphate AMP or guanosine monophosphate GMP. It’s a 2 step process (there’s a diagram in textbook). What you need to know is (1) AMP uses GTP as an energy source and GMP uses ATP as its energy source. It’s reversed. (2) to make AMP you need to use enzyme adenylosuccinate synthase (which is inhibited by AMP) and to make GMP you need to use IMP dehydrogenase (inhibited by GMP). The inhibitory mechanism is to keep equal amounts of AMP and GMP. Too much production of one will promote the production of the other. If you have adequate amounts of both, the aminotransferase step is turned off.
èInhibition of Purine Synthesis
Ok, so you learned how to create purine nucleotides. Why on earth do you want to learn how to inhibit it? It’s inhibition means your death because no purine nucleotides means no DNA. Thankfully, that’s where N^10-formylTHF comes in (look at step 3 of purine synthesis if you already forgot…). These are used as “markers” for the drugs you’ll be taking against bacteria. Example, Sulfonamides are analogs of para-aminobenzoic acid that competitively inhibits bacterial synthesis of folic acid. No folic acid means slow production of purines because THF is used as a coenzyme (as mentioned in step 3) to make purines. This will decrease bacterial replication.
èhumans DON’T synthesize THF (we get it from our diet). So we don’t get dominated by sulfonamides like bacteria do.
We DO get dominated by methotrexate. It’s a cancer treatment that’s also toxic to normal cells. Its pathway inhibits the reduction of THF. You need to keep THF reduced in order for it to work.
èConversion of Nucleoside Monophosphate to Nucleoside Diphosphate & Triphosphates
You have AMP and GMP. You want to make it to either ADP/ATP or GDP/GTP. You want to do this because ATP and GTP are sources of energy. You can’t push a reaction forward using AMP/GMP. Without ATP/GTP half your body’s reactions won’t work è death.
-To convert nucleoside monophosphate è di/triphosphates you need the enzyme nucleoside monophosphate kinase.
Example: adenylate kinase is used to keep ATP/ADP/AMP levels in equilibrium.
-To interconvert diphosphates and triphosphates you need the enzyme nucleoside diphosphate kinase. This has broad specificity.
èSalvage Pathways of Purines
What and why do you need “salvage” pathways? On top of synthesizing purines (which is what I’ve been talking about in the last page), you ingest hundreds, maybe even millions (whoa.) of purines each day. Your body doesn’t want to throw these away, so it converts it to nucleoside triphosphates (ATP/GTP) so it can be used in the body. Hence, your “salvaging ” purines. To make ATP/GTP via salvage pathway, you just need to attach a ribose-5-phosposphate ring to it, PRPP. Use the enzyme adenine phosphoribosyl transferase (APRT) to make ATP or hypoxanthine-guanine phosphoribosyl transferase (HGPRT) to make GTP.
Another reason why your body doesn’t want to “throw away” purines is because you can’t just “THROW AWAY” purines. You need to convert it to uric acid before you can pee it out. Uric acid fucks up your body in more ways than 1 if it accumulates.
è Syndromes and Disorder Disorder Associated with the Above
Lesch-Nyhan Syndrome- is and X-linked, recessive disorder caused by deficiency in HGPRT. Remember when I said you can’t just “throw away” purines because it will eventually lead to a fucked up body? Well I did mention it, and if you’re deficient in HGPRT it means an increase in guanine and hypoxanthine. An increase in these purines will increase uric acid levels because you’re metabolizing purines instead of salvaging it.
(1) increase PRPP levels- because it’s not being used to salvage guanine and hypoxanthine. An increase in PRPP will further promote purine synthesis (it’s a purine synthesis substrate)
(2) There will be a decrease of purine synthesis inhibitors (IMP/GMP) and so this will further fuel the purine synthesis pathway
These 2 facts will create hyperuricemia. Uric acid stones will form in the kidneys, deposition of urate crystals will be stored in joints and soft tissues è your body will be fucked in more ways than 1.
èSynthesis of Deoxyribonucleotides
We’ve—I’ve been talking about ribonucleotides this entire time. DNA doesn’t use ribonucleotides. It uses DEOXYribonucleotides. The synthesis of deoxyribonucleotides only occurs during S-phase of the cell cycle, so you will only see the enzyme ribonucleotide reductase during the S-phase of the cell cycle. This enzyme has nonidentical dimeric subunits R1 & R2. It is specific to nucleoside diphosphates EXCEPT(!!) thymine diphosphate.
Ribonucleotide reductase, reduces nucleoside diphosphates by using 2 hydrogens on its sulfhydryl groups. They become disulfide bonds after the redox reaction. Ok, now I’m going to speak English. Basically ribonucleotide reductase reduces nucleoside diphosphates to make deoxyribonucleotides.
Thioredoxin is a coenzyme to keep ribonucleotide reductase in its reduced form. If ribonucleotide reductase is in it’s oxidized form, it can’t reduce nucleoside diphosphates anymore. Thioredoxin reductase uses NADPH to keep thioredoxin in it’s reduced state. You need BOTH to keep ribonucleotide reductase working.
Example: you have ATP but your cell is in S-phase mode. You need to turn that ATP in to dexoyadenosine triphosphate (dATP) so you can stick it on a newly synthesized DNA (for replication). ATP + ribonucleotide reductase = dATP. Yup it’s that simple.
èRegulation of Deoxyribonucleotide Synthesis
Ribonucleotide reductase has an active site and an allosteric site. Active site is inhibited by dATP (one of its products). This prevents it from making any of the other 4dNTPs. ATP (the substrate) activates this enzyme. The allosteric site regulates substrate specificity and increases conversion of different species of ribonucleotides è deoxyribonucleotides.
èDegradation of Purine Nucleotides
Degradation of nucleic acids occurs in the small intestine where enzymes hydrolyze nucleic acids to nucleotides/sides/ and free bases. Uric acid becomes the end product. The pancreas secretes:
hydrolyze DNA/RNA è oligonucleotides
hydrolyze oligonucleotides è 3’-5’ mononucleotides
(3) intestinal mucosa nucleotides
dephosphorylates hydrolytically è nucleosides and free bases
The free bases are usually not used and are converted to uric acid. It’s eventually excreted in the urine.
èFormation of Uric Acid & Genetic Disorder Disorder
(1) convert AMPè IMP by removing amino group
(2) convert IMP/GMP to nucleosides (inosine & guanosine)
(3)convert inosine & guanosine è purine bases (guanine)
purine nucleoside phosphorylase
(4)guanine needs to be deaminated to xanthine
(5) Hypoxanthine is oxidized by xanthine oxidase è Xanthine. Use xanthine oxidase again è uric acid.
Gout- disease where there’s an increase level of uric acid. It gets deposited into a person’s joints (urate crystals) and causes acute (and eventually chronic) gouty arthritis. Monosodium urate crystals can be deposited into soft tissues è tophaceous gout. Uric acid stones in kidneys. Gout is caused by 2 ways: (1) under excretion (which is more common) and (2) over production.
Over production is caused by x-linked PRPP synthetase that either increases the affinity to ribose-5-P (decrease km) or decrease sensitivity for its inhibitors (purines) è leads to increase uric acid. Secondary to hyperuricemia is increase in purines. Von-Gierk disease or fructose intolerance.
Treatment for acute attacks is anti-inflammatory, chchicine-prednisone, non-steroidal indomethacin. Probenecid/fulfinpyrazone increases renal excretion. Allopurinol are used on over-producers to inhibit synthesis of uric acid by inhibiting xanthine oxidase.
Adenosine deaminase (ADA) deficiency- accumulation of adenosine because lack of ADA. dATP increases, ribonucleotide reductase is inhibited, NO DNA production. Lymphocytes are most affected. Eventually you’ll end up with SCID- severe combined immunodeficiency disease.
èPyrimidine Synthesis & Degradation
The pyrimidine ring is made BEFORE attaching it to ribose-5-P. So you make the pyrimidine ring first THEN attach it to PRPP. This is different from the purines. Glutamine + CO2 + aspartic acid = pyrimidine. Steps:
(1)Rate limiting!!! If you don’t learn anything from these notes at least memorize this enzyme carbomyl-phosphate synthetase (CPS) II . It is inhibited by UTP (it’s end product) and activated by PRPP.
(2)Synthesis of orotic acid –( 2nd step) make carbamoylaspartate using aspartate transcarbamoylase. Then close the pyrimidine ring using dihydroorotase. Oxidize the ring to make it orotic acid. Orotic acid goes to the inner mitochondria membrane because that’s where the enzyme dihydroorate dehydrogenase is è orotate.
(3) Orotate phosphoribose-transferase makes OMP (the parent pyrimidine nucleotide).
a. OMP è UMP with orotidylate decarboxylase
b. Deficiency in either 2 will give you orotic acid in urine
You have UMP but you want UTP. So just phosphorylate. UDP is a substrate for ribonuclotide reductase (this is for making DEOXYnucleotides). dUDP è phosphorylated dUTP è rapidly hydrolyzed to dUMP by using UTP diphosphatase/dUTPase. It’s important because dUMP reduces available dUTP to be incorporated into DNA. That’s a bad thing because our DNA doesn’t want uracil (dUTP) in the base pairing. It’ll cause mutations if dUTP isn’t rapidly hydrolyzed to dUMP.
èSynthesis of UTP and Cytidine Triphosphate (CTP)
Right now you only know how to make the pyrimidine, uracil. To produce CTP you need to aminate (add N) UTP using CTP synthetase + glutamine. Some CTP needs to be converted to CDP (use the enzyme nucleoside diphosphate kinase. Remember? Well I mentioned it during “conversion of nucleoside monoèdi/triphosphate”) so it can be a substrate for ribonuclotide reductase (remember this converts ribonuclotides do DEOXYribonucleotides) è dCDP è dCTP è incorporate into DNA during replication (when during cell cycle?? S-PHASE.)
èSynthesis of Thyamidine monophosphate (TMP) from dUMP
dUMP èdTMP by thymidylate synthase. This enzyme uses tetrahydrofolate (THF) for its carbon unit and 2 hydrogens. THF becomes DHF and can be reduced again to THF by dihydrofolate reductase. Blocking THF by using 5’-florouracil will decrease amount of THF. This will lead to no thymine AND purine è decrease in DNA synthesis.
èSalvage of Pyrimidines- use nucleoside kinases that use ATP to phosphorylate nucleoside è nucleotides.
èDegradation of pyrimidine nucleotides
You need to open the pyrimidine ring to make it soluble. You’ll create beta-alanine and beta-aminoisobutyrate è NH3 + CO2
If you have questions/comments/concerns I’ll be forever at McDoU. Or get my number…so call me maybe. Remember dapat walang hiya.
Membrane potential and Action Potential
Before you read about membrane potentials and action potentials you need to know the physics behind why they actually happen. Even before you find out the physics behind it all, remember there is high [K+] INSIDE the cell and there is low [Na+] INSIDE the cell. It’s opposite in the ECF. This is why Na+/K+ Pump uses ATP. It pumps 3 Na+ OUTSIDE the cell (where [Na+] is already high) and it forces 2 K+ into the cell (even though [K+] is already high inside the cell).
Basic Physics of Action Potentials
èA concentration difference across a selectively permeable membrane, can create a membrane potential.
If a membrane is permeable to only K+, than normally K+ would want to leak out of the cell. Once it moves out, it will create a positive electro gradient outside the cell because the negatively charged proteins will stay inside the cell. Diffusion potential will block further leakage of K+ ions out of the cell even though there is still higher concentration of K+ inside the cell. Potential difference (in a regular mammalian nerve fiber) required is about -94mV. I can use the same example using Na+, but Na+ would leak inside the cell, creates a positive electro chemical gradient inside the cell, until diffusion potential blocks the leakage, even though [Na+] is still higher outside the cell ect. Potential difference (in a regular mammalian nerve fiber) is about +61 mV.
Nernst equation: can calculate the potential of any univalent ion at normal body temperature (98.6F/37C) è EMF (mV) = +/- 61 x log ( [inside]/ [outside]). Assume that (1) temperature is normal levels (2)potential outside the cell = 0 (3) potential it measures is the inside of the cell. + sign if ion is negative, - if the ion is positive.
When you want to measure different ions use Goldman’s equation. The potential difference depends on (1) polarity of the ion (2) the permeability of the membrane (3) concentration of the membrane.
Resting Membrane Potential of Nerves
èThe total resting membrane potential is -90mV.
Remember the Potential difference of K+ (-94) and Na+ (+61) but since the membrane is 100 times more permeable to K+ than the potential difference becomes (-86mV), which makes sense because it’s closer to K+’s (-94). The Na/K Pump pumps 3Na out and 2K+ in with a net difference of -4. The total resting membrane potential is -90mV.
Part of the factors that determine the level of resting potential is the active transport of Na+/K+ pump. This pump is electrogenic meaning that it creates an electric gradient by pumping more positive ions out (3Na+ out/ 2K+in). There’s also a leakage of K+ through the nerve membrane. Potassium “leak” channels allow K+ to leak out even in a resting cell. Na+ can also leak out but K+ is more permeable, so that doesn’t really happen much. If you only account for the “leak” channels of K+ and Na+, then the resting membrane would be -86mV and K+ contributing more to the membrane potential than Na+. But if you add the Na+/K+ pump which pumps 3Na+ out and only 2K+ in, than it will cause the membrane potential to be -90mV (add an extra -4 charge inside the cell). In a resting cell the Na+/K+ pump is working so even in a resting cell, it still uses ATP.
èNerve Action Potential
Resting stage- the membrane is polarized -90mV
Depolarization stage- Is when Na+ suddenly becomes permeable and the membrane gains + charge because of it. Sometimes certain cells overshoot the 0mV and go up to +35mV but in small fibers, and in many CNS neurons, the potential merely reaches 0.
Repolarization Stage- when the Na+ channels close and the K+ channels open more than normal. The influx of K+ ions lets the membrane get back to original resting state.
· Voltage-gated Sodium Channel- this channel has 2 gates. One on the outside of the cell called the activation gate and one on the inside, the inactivation gate. At resting state the activation gates are closed. When the resting state becomes about -70 to -50mV (threshold), there is a conformation change that will open the gate fully, the activation gate opens. This is called the activated state and it increases Na+ permeability to 500-5000 fold. The inactivation of the channel will close when the membrane potential reaches about +35, here the activation gate stays open while the inactivation gate closes. The inactivation process means the inactivation gates will not reopen until the membrane potential becomes resting levels.
· Voltage-gated Potassium Channel- when the membrane potential goes from negative 90mV close to 0, the K+ channels undergoes a confirmation change that will open the channel. The decrease in Na+ entry and the simultaneous increase in K+ exit form the cell combine to speed repolarization.
èRoles of other Ions During Action Potential
Negatively charged ions (anions)(eg. Sulfate compounds, organic phosphate compounds, ect.) inside the nerve axon is one of the causes that makes the membrane potential negative. Calcium ions are used in some cells in place of Na+. Same thing happens to Ca++ like with Na+. The Ca++ will pump Ca++ out the cell. There is about 1000-fold Ca++ outside the cell than inside, so when voltage-gated Ca channels open, there will be a flow of Ca++ inside the cell. These channels are also called slow channels because it takes 10-20 times longer for activation. Ca++ are numerous in cardiac muscles and smooth muscles. There is an increase in Na+ channels when there is a deficiency in Ca++. When there’s a deficit of Ca++, the Na+ channels will become activated (open) by a small increase of the membrane potential from its normal, very negative level. This causes the fiber to become highly excitable and cause spontaneous discharge. This spontaneous discharge is called muscle “tetany” . This is sometimes lethal because it causes contraction of respiratory muscles.
Positive-feedback Cycle Opens the Sodium Channels. When the potential from -90mV gets close to 0mV, then Na+ channels will start to open. This will cause even more voltage-gated Na+ channels to open. This is a positive feedback cycle that continues until all the voltage-gated Na+ channels are open. A potential will occur when Na+ ions entering the fiber becomes greater than the K+ions leaving the fiber. This doesn’t occur until about -65mV so this is called the threshold.
èPropagation of the Action Potential
When a nerve fiber gets excited, Na+ will rush into a part of the cell. This makes part of the cell reach -65mV threshold and cause an action potential, and then because of the positive charge in this area of the cell, it will open other Na+ channels around the area. This is why an action potential travels along a nerve fiber. It is called a nerve or muscle impulse.
The direction of propagation can go either way. There all-or-nothing response means that an action potential will be administered only if all the conditions are met. The ratio between action potential : threshold for excitation must be greater than 1. This is called the safety factor.
èRe-establishing Na+ and K+ ionic gradients after action potentials are completed—importance of Energy metabolism.
Re-establishing ionic gradients is due to the Na+/K+ pumps. This “recharging” of the nerve fiber uses ATP. The activity of the pump increases when there’s a lot of Na+ inside the cell. If the [Na+] rises it can increase the pump’s activity eightfold.
èPlateau in Some Action Potentials
Sometimes the excited membrane doesn’t repolarize immediately after depolarization. It sometimes remains on a plateau near the peak of the potential. This type of action potential occurs in the heart muscle fibers. The cause is a combination of (1) Na+ channels, fast channels (2) Ca++ channels, slow channels. Opening of fast channels causes the spike portion of the action potential, and the prolonged opening of the slow Ca++/Na+ channels allows Ca++ to enter the fiber, which is largely responsible for the plateau portion of the action potential as well. (3) The K+ channels are slower than usual to open.
èRythmicity of Some Excitable Tissues – Repetitive Discharge
(1) heart (2) peristalsis of intestines (3) neuronal events of control , like breathing. Other tissues can discharge repetitively if the threshold for stimulation is reduced low enough. Large muscle fibers can discharge repetitively when they are placed in a solution that contains the drug veratrine or when [Ca++] falls below critical value, both increases Na+ permeability of the membrane.
For spontaneous rhythmicity to occur, the membrane must be permeable enough to Na+ ions, or to Ca++ and Na+ ions (through the slow gates). For the heart -60 to -70mV (1) Na+ and Ca++ flow inward (2) this increases membrane voltage in the positive direction which increases permeability (3) even more ions flow inward (4) permeability increases more until AP is generated. Then the membrane repolarizes. The AP doesn’t happen immediately after because of repolarization. In this state, self-re-excitation cannot occur.
Myelinated fibers causes salutatory conduction. This increases the speed at which an action potential occurs and it also conserves energy. Absolute refractory period is when an AP cannot be elicited even with a strong stimulus.
Alimentary mnemonics (Anatomy) » FC Barcelona style
Last season 2010-11 Dani Alves (FC Barcelona) made us hold our bowel components just so we can find out if he would renew his contract.
“Dani Just Increased Annual Cash Signing Reports”.
From proximal to distal
Duodenum Jejunum Ileum Appendix Colon Sigmoid Rectum
Diaphragm apertures : spinal levels
Aortic hiatus = 12 letters = T12
Oesophagus = 10 letters = T10
Vena cava = 8 letters = T8
Duodenum: lengths of parts
“1-4 in a circle”: (because 3 FCB players pass in circles around 1 FCB piggy > piggy in the middle game, how la masia to 1st team practice)
1st part : 2 inches
2nd part : 3 inches
3rd part : 4 inches
4th part : 1 inch
Gut intrinsic innervation functions: M to M, S to S
Myenteric plexus: Motility
Submucosal plexus: Secretion
2 feet from end of ileum
2 types of tissues may be present
2 -wice more common in males
2% occurrence in population
On DNA: Replication, Transcription, Translation
DNA has 3 main functions to support all forms of life. Replicationis the duplication of DNA parental strand using a semi-conservativemodel. Transcriptionis when DNA is copied into mRNA, which are information carrying intermediates in protein synthesis. Translationis the synthesis of proteins according to instructions given by mRNA templates. Monomers in protein are nucleotidesand DNA/RNA are polymers with poly nucleotides. Each has a base, phosphate, and sugar. Learn to draw and pair AT, CG bases usinghydrogen bonds. In a stick an P model the bottom of the stick is carbon 5, where the phosphate is linked by an ester bond.