Proteins are polymers of amino acids (AA's). A very small protein, insulin, has 87 AA's in the polymer; a relatively large protein, one of the smaller contractile proteins from intercostal (striated) muscles of a rabbit lumbar region, has 247 AA's in the polymer. Any polymer of amino acids can be called a polypeptide. I prefer to limit the term protein to those polypeptides which have Biological significance, and will do so for the remainder of these lectures.
Amino acids are organic molecules, with 1 Carbon (C) atom, plus an amino group (-NH2) and
an acid group (our old friend, -(C=O)-OH). In the center between the amino and the acid, we place our
single Carbon atom (-C-) and call it the central carbon [because it is roughly centered between the
two radicals, not exactly centered due to things like electronegativity & bond length]. We usually
put the amino on the left and the acid on the right:
H2N-(HC-)-COOH, or H2N-(HC-)-(C=O)-OH,
where the central -(HC-)- is meant to represent a C with an H on one side (up) and an unused bond location on the other side (down). To the unused bond location we attach a ‘side chain’ or radical (R):
The side chain may be simple, branched, or even a ring structure containing Carbon, Hydrogen, Oxygen, and sometimes Nitrogen or Sulfur. Of the many AA's known to exist, only 20 are commonly found in proteins. The chemical structures [which differ in their side chains (-R)] of these 20 AA's are probably not in your A & P notes, but can be found in most A & P texts, or intro Biology texts [if you care, or even if you don't really care].
Amino acids are polymerized, as usual, by dehydration. One Hydrogen (H) is removed from the amino group on the second AA, and the hydroxyl (OH) is removed from the acid group on the first AA. The Nitrogen (N) of amino group is then bonded to the Carbon (C) of the acid group [using the -(NH)- to indicate that the other H is to the side]:
H-(NH)-(HCR)-(CO)-(NH)-(HCR)-(CO)-OH   +   H-OH
The N-C bond is called a peptide bond, because peptic is the Greek term for the contents of the stomach (especially when the contents have been rejected by the stomach via reverse peristalysis). Before Biologists knew Chemistry, the enzyme which digests protein in the stomach was named ‘peptic juice.’ When Biologists started learning Chemistry, we changed the name of the enzyme to peptase, for ‘stomach enzyme,’ and adopted the name peptide bond for the bond digested by peptase. The polymer of AA's ought to be called a poly-amino acid, but we didn't know chemistry very well, so improperly named the polymer a polypeptide. A dipetide has 2 AA's, but only one peptide bond [Another example of “interesting” trivia which you are welcome to ignore at your pleasure]. A non-trivial tidbit [which you may also ignore] is that the AA's in a polypeptide (or protein) are numbered from the amino-end, and the polypeptides are assembled by ribosomes from the amino-end. I am not sure whether they are digested from the acid-end, or a random locations [although I suspect it is random]. The baby-friendly “proteins” in some baby formula and first ‘solid’ foods are actually proteins which have been digested to shorter [and more easily digested] polypeptides. “Aged” protein foods, such as tender beef and cheese also have pre-digested polypeptides, where mold is used to do the digesting. When beef hangs in the locker plant [as in one of the Rocky movies; The side of beef Rocky used as a punching bag would make very tender, melt-in-your-mouth steaks], it becomes fuzzy green. The fuzz is scraped off, and some of the beef proteins have been digested to more easily digested polypeptides. You can also ‘tenderize’ beef (or any red meat) by adding protein-digesting enzymes from plants (such as Adolph's meat tenderizer or garlic) as a rub [which works better if you repeatedly stab the meat with a fork as you apply the rub]. Likewise, milk solids (curds [whey is lactose-rich skim milk, and curds are “milk solids” (rich in proteins and lipids)] are separated from whey by adding vinegar (acetic acid solution) less than 1 cup per gallon of whole milk] are filtered out of the curds and whey by pouring through cheese cloth (with rather large holes between the threads), then wrapping the curds in the cheese cloth and hanging it in a cold, dark place until it becomes fuzzy green. Most of the fuzz is removed by peeling off the cheese cloth, exposing the cheese. The cheese is then wrapped in wax to slow the growth of the mold (by restricting the air supply). If you leave real cheese [not American processed cheese] in the refrigerator too long, it again becomes fuzzy green. You can safely slice off the fuzzy green parts and eat the now sharper cheese [if the fuzzy parts are black, you should discard the cheese rather than eat it; if the fuzz is any other color, you are gambling if you eat the cheese]. If you skip the molding process, and rinse the curds, still in the cheese cloth, with water, you get cottage cheese. ‘Spoiled’ cottage cheese is called yogurt (and is spoiled by growth of Lactobacillus). American process cheese (most pre-packaged cheese slices and cheese spreads, such as Velvetta or CheeseWhiz) will not grow mold, but will support bacterial growth and accumulation of bacterial toxins. Spoiled processed cheese cannot be eaten safely!
The numbering of the AA's allows us to write down the sequence of the AA's in a protein, which we want to do because the sequence is extremely important to the function of the protein. Each different protein has a unique sequence, even similar proteins from different species. Beef insulin differs from Human insulin by substitution of 4 AA's at non-critical locations, so beef insulin has been used to treat Human diabetics. Sheep insulin differs from Human insulin by 6 substitutions, two of which are in critical locations, so sheep insulin does not work well in Human diabetics. Because of the differences in proteins between species, each species has a unique ratio of the 20 key AA's. The dietary intake of protein must duplicate the correct Human ratio of AA's to provide maximum health. This also applies to pet foods, so I am unsure how cereal [and even vegetables] added to cat food is supposed to be good for a carnivorous cat. Fortunately, cats and dogs don't read Nutrition textbooks, and don't realize that Human-like diets may not be healthy for them -and they still manage to keep setting new records for longevity. A “typical” [that is, a theoretical] Human requires about one serving of red meat per week to get the correct ratio of amino acids in their diet. One serving was once called a ‘petite’ steak on restaurant menus, and is no larger than 6 oz; not half a cow. Some friends of mine used to have ‘contests’ to see who could eat the largest slab of roast beef tenderloin; all but one has now had their first (or more) heart attack, and he is being treated to prevent the heart attack after his first angina pectoris. While they were working on their heart attacks, I would order a white fish, eat half of it and take the other half home for a second meal [a single serving according to the menu was a whole fish, although nutritionally a single serving is one filet, or less for most white fish which tend to large compared to a perch].
While semi-vegetarian cats are a puzzlement to me, even more mysterious are vegetarian Humans. Anatomically and physiologically, Humans are omnivores [this means a Human can, and should, eat anything that doesn't eat them first (except for poisonous things, which sort of eat you after you eat them). You have incisors for chopping vegetables (think rabbit, or even beaver, buck-teeth), and canines (think “Lions and Tigers and Bears, oh my!”) for ripping the flesh off Kentucky-Fried chicken drumsticks. Your single stomach produces larger amounts of peptase than do cows (with four stomachs for digesting grasses and weeds). You have a moderate sized appendix, the same size (in volume not proportion of body size) as vegee-eating laboratory white rats, for storing the bacteria that assist in digesting fiber from lettuce. While you can eat anything that doesn't eat you first, I do not recommend attempting to eat alligators in the wilds of Florida, nor the sharks offshore from Florida, but there is a certain, almost evil, pleasure in eating either one in restaurants in Asheville, North Carolina [the Asheville restaurants are from personal experience, and I have encountered a few wild alligators in Florida but I never met a shark without a thick glass wall between us]. True vegetarian and vegan diets can not, in theory, provide the minimum dietary intake of all essential [see text, table 15-2, pg. 15-4] AA's without also providing more than the maximum tolerable dose of some AA's [see text pg. 15-9]. Again, reality seems to contradict theory in that many religious and cultural groups have managed to live for 100's of generations on vegetarian diets. What has not been established with scientific rigor is that these groups function at optimal health.
Proteins come in two styles: structural proteins and enzymatic proteins. Most dietary protein comes
from structural proteins (in the food organisms), and is digested to AA's and polypeptides. The amino
acids are absorbed, but since storage of amino acids is limited, most are used soon after being
absorbed or are excreted. Those AA's which are used perform only two [not four] major functions, and
one minor function.
Of the functions listed in your text (Table 15.1, pg. 15-3) numbers 1 & 3 are the same function: the AA's are used by ribosomes [mostly free ribosomes] to synthesize structural proteins, either to build new tissues (number 1 in text) or to replace damaged proteins in existing tissues (number 3 in text). The need for replacement structural proteins is high simply because all chemical compounds containing Nitrogen are unstable [perhaps the most unstable is trinitro-toulene, commonly called TNT]. Each amino acid contains at least one Nitrogen (the one in the amino group), and are thus unstable, with a tendency for the peptide bonds to break spontaneously -yielding two polypeptides. The broken bonds cannot be repaired by any known living creature, so the polypeptides are digested to AA's, while a replacement molecule is being synthesized by free ribosomes at the location where the ‘old’ protein failed. Most of the AA's from the ‘old’ protein are reclaimed for the next protein being assembled. This is why you can lose and replace 9 oz protein per day (text, pg. 15-3f [the “f” means “and following page”, and “ff” would mean “and following pages”]), yet absorb only about 2 to 3 oz protein per day.
The second function of proteins listed in the text uses the second type of protein, the enzymatic protein. Again ribosomes (this time attached ribosomes) assemble AA's into enzymatic proteins, which are dumped into the endoplasmic reticulum (e.r.) to be withdrawn by any part of the cell needing that particular enzyme, or are stored in the Golgi complex to be secreted into the lumen of a secretory organ. Now the instability of proteins becomes an advantage, because soon after these enzymes begin being used, they break down into non-functional polypeptides, and whatever reaction(s) they catalyze slow then stop, unless more enzyme is provided to continue the reactions. And again, the polypeptide fragments of a former enzyme are digested to AA's which become available for the next protein being assembled.
Structural proteins must be of the correct size and shape in order to fit into the larger structure (such as a cell) being built or repaired [something about square pegs and round holes]. Enzymatic proteins, as predicted by the Lock and Key hypothesis, must have the correct size and shape to fit onto the substrate and bring the active site adjacent to the bond to be formed or broken [the key must fit the key hole, and the notches must match the tumblers inside the lock]. In a word, shape is important for the ability of a protein to serve its purpose. Protein structure comes as primary, secondary, tertiary, and sometimes quaternary. Primary structure is the AA sequence which is assembled by the ribosomes into a linear [remember zig and zag] molecule. For insulin, this is 87 AA's, which make up the primary structure of inactive insulin. Secondary structure results as the levo-rotary zigs cause the long molecule to coil around itself, and form Hydrogen bonds [more Chemistry not found in your A & P notes, but probably in your A & P textbook]. For insulin, the secondary structure of the inactive form is ‘pretzel’-shaped (and still 87 AA's long). The tertiary shape is formed after 36 AA's are removed from the single curve side of the pretzel [as opposed to the double curve side], leaving a 21 AA piece and a 30 AA piece which fold on each other and bond together into a complex, roughly bow-tie shaped structure. This is the active form of insulin which mediates the conversion of glucose to glycogen. If it were less complicated, and ribosomes made the 51 AA active form, glucose would always be converted to glycogen, leaving none in the serum. The entire Human species would be dying in a diabetic coma, or would be already dead; translated to English, we would be extinct, which we are not. For those proteins with quaternary structure, two or more polypeptides are Hydrogen-bonded together to form a large functional structure. To explain the importance of AA sequence to introductory Biology students [or students in a College-prep High School], I came up with the following headline:
“MIJORITY APPROVE PRESIDENT'S POLUCY”
which has two typographical errors (one critical, one non-critical). So your challenge is to determine whether or not the President is still popular. Starting with the non-critical error, the U in POLUCY clearly should be an I in POLICY:
“MIJORITY APPROVE PRESIDENT'S POLUCY”
“MIJORITY APPROVE PRESIDENT'S POLICY”
The above error was ‘non-critical’ because we could make sense of the word before we corrected the error. The other error is critical because there are two possible errors, and correcting them produces opposite meanings:
either (1) the first I in MIJORITY should be an A:
“MIJORITY APPROVE PRESIDENT'S POLICY”
“MAJORITY APPROVE PRESIDENT'S POLICY”
in which case the president is still popular,
or (2) the J in MIJORITY should be an N:
“MIJORITY APPROVE PRESIDENT'S POLICY”
“MINORITY APPROVE PRESIDENT'S POLICY”
in which case the President is no longer popular [he/she was popular (or “POP-u-lur” if you've seen Wicked) at one time, at least before the election]. The headline as written cannot be interpreted with more than a 50-50 chance of being correct. A single ‘typo’ in a protein can be corrected [in theory] with a 1 in 20 chance of being correct. In real living creatures, errors in proteins are corrected by running them through the paper shredder.
Protein, or more accurately, amino acids, can be used as an energy source, but in the real world
[where actual, living Humans are found], this is limited to emergency situations, such as
carbohydrate starvation. Unfortunately, the only substrate for the metabolic processes which capture
energy in a useful form (ATP's) is sugar, or anything that looks chemically like sugar. Amino acids
look nothing like sugar due to the Nitrogen-containing amino group. The amino group can be removed by
hydrolysis, by splitting a water (H-OH) into a Hydrogen (H-) and a hydroxyl (-OH) [like separating a
Nabisco Oreo (or Sunshine Hydrox cookie) into a chocolate cookie and a chocolate cookie
with cream filing on it (the Hydrox cookie is a good mneumonic for remembering the Hydrox-yl
These are both free radicals [capable of destroying vital chemical bonds in Humans] which break
peptide bonds and place the Hydrogen (H-) on the amine (-NH2) making NH3, or
Ammonia. The hydroxyl (-OH) is attached to the central Carbon of the amino acid making a deaminated
amino acid HO-(HCR)-(C=O)-OH, which then is converted [at the expense of several
ATP's] to a sugar-like substance and metabolized to yield ATP's, but net production is less than what
you would get from a perfectly good carbohydrate. The Ammonia is highly toxic; it's the ingredient in
Windex (and other cleaning products) that is responsible for the burning sensation in your eyes
and nose, [as tissue damage begins]. The Ammonia is immediatedly converted [at an additional cost of
ATP's] to urea, which only poisonous enough to kill you (uremic poisoning). Under normal conditions,
the urea is diluted with water to make urine [a solution of urea & water], and excreted through
the kidneys and sweat glands, producing an unpleasant body odor.
When Humans are forced into using protein as their primary energy source due to actual starvation a number of problems arise. [a 100 g bowl of brown rice provides about 362 Calories, so 3 bowls of rice during a “good” week barely meets the absolute minimum Calorie intake need of 800 Cal for one DAY; some starving children in developing countries do get 3 bowls, 300 g, of rice a week, or less. First, the amino acid sources are damaged proteins [which are not replaced because of a dietary deficiency of protein [brown rice provides 7 g of incomplete protein per 100 g rice; the polished white rice shown in the TV commercials for Children's charities provide only 6.8 g incomplete protein per 100 g serving (data from FAO Food and Nutrition Division, Food and Agriculture Organization of the United Nations, Rome, Italy); a 100 g top sirloin steak provides 29.4 g of protein (data from highproteinfoods.net)]; in other words, the protein source used for energy is the patient's body! Probably depending on genetics, the excess urea produced (beyond what can be removed by the now poorly functioning kidneys) may be converted to uric acid, resulting in the total body endema associated with kwashiorkor [in mild cases, the edema is confined to the lower extremities and is called gout]; otherwise, the patient develops marasmus due to loss of muscle and other tissues. Both kwashiorkor and marasmus are fatal, unless reversed by early intervention with an aggresive nutritionally sound diet.
When Humans are forced into utilizing protein as their primary energy source on purpose [this sometimes occurs in the magical fantasy world of easy weight loss programs], (surprise, surprise!) the amino acid source used is polypeptides from damaged protein -not dietary protein. Unneeded amino acids from digestion are not absorbed, because amino acids are absorbed by active transport rather than the passive (or facilitated) absorption used for sugars and fatty acids. Surplus amino acids from digestion are used to enrich the fecal material. Since the body cannot distinquish between actual (carbohydrate) starvation due to inadequate food supply and induced carbohydrate starvation recommended by ‘weight management counselors,’ the effects on the body are the same. The amino acids which are deaminated to be used for energy capture come from the patient's muscle mass (and other organs, including vital organs such as hearts). While the loss of muscle mass does produce weight loss, the body fat percentage increases initially [remember, a drop in carbohydrate density in the food intake triggers fat deposition into adipose]. Long term deliberate carbohydrate starvation will eventually drive mobilization of adipose fat as a energy source, but the damage due to amino acid utilization will not reverse [and will continue] until the body believes that winter is over [detected by an sizable increase in carbohydrate density of the food intake]. Back in the real world, winter usually lasts less than 6 months (it only feels longer), so cavemen survived the Pleistocene Ice Age, reproduced, and Homo sapiens is still here. By the way, the high protein weight loss diets typically use the presence of ketones in the urine as an indicator that the diet is “working;” and urinary ketones is the first sign (as opposed to symptom, for those of you who know the difference) of uremic poisoning, leading to a Nursing diagnosis, followed by intervention to reverse the problem, because it is a treatable, but potentially life-threatening, medical condition.
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revised: 10 Nov 2009