Posts Tagged ‘biochemistry’

Guest post: Dr. Eugene J. Fine

Last time I discussed our pilot study showing the effects of carbohydrate (CHO) restriction & insulin inhibition (INSINH) in patients with advanced cancers.  We described how the molecular effects of INSINH plus systemic (total body) effects like ketosis might inhibit cancer growth. My goal now is to present the underlying hypothesis behind the idea with the goal of understanding how patients with cancers might respond if we inhibited insulin’s actions? Should all patients respond? If not, why not? Might some patients get worse? These ideas were described briefly in our publication describing our pilot protocol. (more…)

In the last post, I had proclaimed a victory for dietary carbohydrate restriction or, more precisely, recognition of its explicit connection with cell signaling. I had anointed the BMC Washington meeting as the historic site for this grand synthesis. It may have been a matter of perception — many researchers in carbohydrate restriction entered the field precisely because it came from the basic biochemistry where the idea was that the key player was the hormone insulin and glucose was the major stimulus for pancreatic secretion of insulin. We had largely ignored the hook-up with cell-biology because of the emphasis on calorie restriction, and it may have only needed getting everybody in the same room to see that the role of insulin in cancer was not separate from its role in carbohydrate restriction. (more…)

It was in July of 2012 that I suddenly realized that we had won, at least scientifically. It was now clear that we had a consistent set of scientific ideas that supported the importance of insulin signaling in basic biochemistry and cell biology and that there was a continuum with the role of dietary carbohydrate restriction in obesity, diabetes or for general health.  The practical considerations, how much to eat of this, how much to eat of that, were still problematical but now we had the kernel of a scientific principle. In fact, it was not so much that we had the answer as that we had the right question.  In science, the question is frequently more important than the answer.  Of course, winning wasn’t the original idea. When my colleagues and I got into this, about ten years ago, coming from basic biochemistry, we hadn’t anticipated that it would be such a battle, that there would be so much resistance to what we thought was normal scientific practice.

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“I do not think I ever met Mr. Hyde?” asked Utterson.

“O, dear no, sir.  He never dines here,” replied the butler. “Indeed we see very little of him on this side of the house; he mostly comes and goes by the laboratory.”

“Well, good-night, Poole.”

“Good-night, Mr. Utterson.” And the lawyer set out homeward with a very heavy heart. “Poor Harry Jekyll,” he thought, “my mind misgives me he is in deep waters!”

                             – Robert Louis Stevenson, Dr. Jekyll and Mr. Hyde.

First off, some of my best friends are pediatricians. No kidding.  But the title of the paper in the International Journal of Obesity caught my eye: “Preventing and treating childhood obesity: time to target fathers.”  Target fathers?  Blaming the patient, at least in the abstract, is standard.  The USDA made it clear that we have perfectly good recommendations and that the fault is in ourselves that we are underachievers. And if you are one of the “diet gurus” (as JAMA refers to us), who think that dietary carbohydrate restriction has promise, you get used to a certain amount of abuse. Still, one is not happy with the family angle.

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(Answers to last week’s organic puzzler at the end of this post).

One of the more remarkable results from Jeff Volek’s laboratory in the past few years was the demonstration that when the blood of volunteers was assayed for saturated fatty acids, those who had been on a low carbohydrate diet had lower levels than those on an isocaloric low-fat diet. This, despite the fact that the low-carbohydrate diet had three times the amount of saturated fat as the low-fat diet. How is this possible? What happened to the saturated fat in the low-carbohydrate diet? Well, that’s what metabolism does. The saturated fat in the low-carbohydrate arm was oxidized while (the real impact of the study) the low-fat arm is making new saturated fatty acid. Volek’s former student Cassandra Forsythe extended the idea by showing how, even under eucaloric conditions (no weight loss) dietary fat has relatively small impact on plasma fat.

The essential point of what I now call the Volek-Westman principle — we should be speaking of basic principles because the idea is more important than specific diets where it is impossible to get any agreement on definitions — the principle is that carbohydrate, directly or indirectly through insulin and other hormones, controls what happens to ingested (or stored) fatty acids. The motto of the Nutrition & Metabolism Society is: “A high fat diet in the presence of carbohydrate is different than a high fat diet in the presence of low carbohydrate.” Widely attributed to me, it is almost certainly something I once said although it has been said by others and the studies from Volek’s lab give you the most telling evidence.

The question is critical. Whereas the scientific evidence now establishes that dietary saturated fat has no effect on cardiovascular disease, obesity or anything else, plasma saturated fatty acids can be a cellular signal and if you study the effect of dietary saturated fatty acids under conditions where carbohydrate is high and/or in rodents where plasma fat better correlates with dietary fat, then you will confuse plasma fat with dietary fat. An important study identified potential cellular elements in control of gene transcription that bear on lipid metabolism.

So, it is important to know about plasma saturated fatty acids. First, recall that strictly speaking there are only saturated fatty acids (SFA) — this is explained in detail in an earlier post.  What is called saturated fats simply mean those fats that have a high percentage of SFAs — things that we identify as “saturated fats,” like butter, are usually only 50 % saturated fatty acids (coconut oil is probably the only fat that is almost entirely saturated fatty acids but because they are medium chain length, they are usually considered a special case).

In Volek’s study, 40 overweight subjects were randomly assigned either to a carbohydrate-restricted diet (abbreviated CRD; %CHO:fat:protein = 12:59:28) or to a low fat diet, (LFD; %CHO:fat:protein = 56:24:20). The group was unusual in that they were all overweight would be characterized as having metabolic syndrome, in particular they all had, atherogenic dyslipidemia, which is the term given to a poor lipid profile (high triacylglycerol (TAG), low HDL-C, high small-dense LDL (so-called pattern B)). Metabolic syndrome (MetS) is the predisposition to CVD and diabetes and is characterized by the constellation of overweight, atherogenic dyslipidemia and, by now, a dozen other markers.

The paper is one of the more striking for the differences in weight loss between two diet regimens. Although participants were not specifically counseled to reduce calories, there was a reduction in total caloric intake in both two groups. The response in weight loss, however, due to the difference in macronutrient composition, was dramatically different in the two groups. The CRD group (labelled as very low carbohydrate ketogenic diet (VLCKD) in the figure) lost twice as much weight on average as the low-fat controls despite the similar caloric intake. Although there was substantial individual variation, 9 of 20 subjects in the CRD (VLCKD) group lost 10% of their starting weight. more than that lost by any of the subjects in the LFD group. In fact, nobody following the LFD lost as much weight as the average for the low-carbohydrate group and, unlike George Bray’s demonstration of caloric inefficiency, whole body fat mass was where the major differences between the CRD (VLCKD) and LF appeared (5.7 kg vs 3.7 kg). Of significance is the observation that fat mass in the abdominal region decreased more in subjects on the CRD than in subjects following the LFD (-828 g vs -506 g). This is one of the more dramatic effects of carbohydrate restriction on weight loss but many have preceded it and these have been frequently criticized for increasing the amount of saturated fat (whether or not any particular study actually increased saturated fat). Although the original “concern” was that this would lead to increased plasma cholesterol, eventually saturated fat became a generalized villain and, insofar as any science was involved, the effects of plasma saturated fat were assumed to be due to dietary saturated fat. The outcome of Volek’s study was surprising. Surprising because the effect was so clear cut (no statistics needed) and because an underlying mechanism could explain the results.

Saturated Fat

The dietary intake of saturated fat for the people on the VLCKD (36 g/day) was threefold higher than that of the people on the LFD (12 g/day). When the relative proportions of circulating SFAs in the triglyceride and cholesterol ester fractions were determined, they were actually lower in the low carb group. Seventeen of 20 subjects on the CRD (VLCKD) showed a decrease in total saturates (the others had low values at baseline) in comparison to half of the subjects consuming the LFD had a decrease in saturates. When the absolute fasting TAG levels are taken into account (low carbohydrate diets reliably reduce TAB=G), the absolute concentration of total saturates in plasma TAG was reduced by 57% in the low carbohydrate arm compared to 24% reduction in the low fat arm who had, in fact, reduced their saturated fat intake. One of the saturated fatty acids of greatest interest was palmitic acid or, in chemical short-hand, 16:0 (16 means that there are 16 carbons and 0 means there are no double bonds, that is, no unsaturation).

So how could this happen? The low fat group reduced their SFA intake by one-third, yet had more SFA in their blood than the low-carbohydrate group who had actually increased intake. Well, we need to look at the next thing in metabolism.

In the post on An Introduction to Metabolism, we made the generalization that there were roughly two kinds of fuel, glucose and acetyl-CoA (the two carbon derivative of acetic acid). The big principle in metabolism was that you could make acetyl-CoA from glucose, but (with some exceptions) you couldn’t make glucose from acetyl-CoA, or more generally, you can make fat from glucose but you can’t make glucose from fat. How do you make fat from glucose? Part of the picture is making new fatty acids, the process known as De Novo Lipogenesis (DNL) or more accurately de novo fatty acid synthesis. The mechanism then involves successively patching together two carbon acetyl-CoA units until you reach the chain length of 16 carbons, palmitic acid. The first step is formation of a three carbon compound, malonyl-CoA, a process which is under the control of insulin. Malonyl-CoA starts the process of DNL but simultaneously prevents oxidation of any fatty acid since, if you are making it, you don’t want to burn it. This can be further processed, among other things, can be elongated to stearic acid (18:0). So this is a reasonable explanation for the increased saturated fatty acid in the low-fat group: the higher carbohydrate diet has higher insulin levels on average, encouraging diversion of calories into fatty acid synthesis and repressing oxidation. How could this be tested?

It turns out that, in addition to elongation, the palmitic acid can be desaturated to make the unsaturated fatty acid, palmitoleic acid (16:1-n7, 16 carbons, one unsaturation at carbon 7) and the same enzyme that catalyzes this reaction will convert stearic acid (18:0) to the unsaturated fatty acid oleic acid (18:1n-7). The enzyme is named for the second reaction stearoyl desaturase-1 (SCD-1; medical students always hate seeing a “-1” since they know 2 and 3 may will have to be learned although, in this case, they are less important). SCD-1 is a membrane-bound enzyme and it seems that it is not swimming around the cell looking for fatty acids but is, rather, closely tied to DNL, that is, it preferentially de-saturates newly formed palmitic acid to palmitoleic acid.

There is very little palmitoleic acid in the diet so its presence in the blood is an indication of SCD-1 activity. The data show a 31% decrease in palmitoleic acid (16:1n-7) in the blood of subjects on the low-carb arm with little overall change in the average response in the low fat group. Saturated fat, in your blood or on your plate?

Forsythe’s paper extended the work by putting men on two different weight-maintaining low-carbohydrate diets for 6 weeks. One of the diets was designed to be high in SFA (high in dairy fat and eggs), and the other, was designed to be higher in unsaturated fat from both polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids (high in fish, nuts, omega-3 enriched eggs, and olive oil). The relative percentages of SFA:MUFA: PUFA were, for the SFA-carbohydrate-restricted diet, 31: 21:5, and for the UFA diet, 17:25:15. The results showed that the major changes in plasma SFA and MUFA were in the plasma TAG fraction although probably much less than might be expected given the nearly two-fold difference in dietary saturated fat and, as the authors point out: “the most striking finding was the lack of association between dietary SFA intake and plasma SFA concentrations.”

So although it is widely said that the type of fat is more important than the amount, the type is not particularly important. But, what about the amount? A widely cited paper by Raatz, et al. suggested, as indicated by the title, that ‘‘Total fat intake modifies plasma fatty acid composition in humans”, but the data in the paper shows that differences between high fat and low fat were in fact minimal (figure below).

The bottom line is that distribution of types of fatty acid in plasma is more dependent on the level of carbohydrate then the level or type of fat. Volek and Forsythe give you a good reason to focus on the carbohydrate content of your diet. What about the type of carbohydrate? In other words, is glycemic index important? Is fructose as bad as they say? We will look at that in a future post in which I will conclude that no change in the type of carbohydrate will ever have the same kind of effect as replacing carbohydrate across the board with fat. I’ll prove it.

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Answers to the organic quiz.

I am currently teaching nutrition and metabolism to first year medical students.  The problem in this subject is the large number of individual reactions which leads students to think of the subject the way somebody described the study of history: just one damned thing after another.  I try to present the big picture and the approach is the systems or “black box”  strategy.  The method is to ask whether we can get some information just by looking at the inputs and outputs to a system even if we don’t know any of the details of what’s going on inside.  In other words, it is a way of organizing limited information.  The method is favored by engineers who are the people most unhappy with the idea that they don’t know anything at all.  First, the big principles.

Metabolism: two goals, two fuels.  

There are two major goals in human energy metabolism: First, to provide energy for life processes in the form of the molecule ATP and second, to provide glucose for those cells that require glucose (particularly brain and central nervous system) and to maintain blood glucose at a relatively constant level: too little is obviously not good but too much is also a problem in that glucose is chemically reactive and can interact with body material, particularly proteins when at high concentrations. Of course, metabolism does many things but these are the two major goals in providing energy.

A second big generalization is that in this process there two kinds of fuels: glucose and acetyl-Coenzyme A (abbreviated acetyl-CoA or sometimes written as acetyl-SCoA; the S, which is meant to show that the compound contains sulfur, is not pronounced).

The black box of life. 

You knew what we do in metabolism even before you started reading this. Putting it into black box terms, you knew: we take in food and we take in oxygen. We excrete CO2 and water.  Somehow this gives us the energy for life as well as the material to build up components of the body.  You don’t have to know too much chemistry to figure out the important conclusion that, inside the black box, living systems use oxidation, just like combustion in a furnace. Lavoisier’s whole animal calorimeter that I described in a previous post was a beautiful real demonstration of this black box.  More technically, this is an oxidation-reduction reaction.  Oxidation, in a biochemical context, means combination with oxygen or loss of hydrogen and reduction means loss of oxygen or gain of hydrogen; we say that the (carbons in the) food gets oxidized and the oxygen gets reduced (to water).  Like the common oxidation reactions you know (combustion in a furnace or an automobile engine), this produces energy which can be used to do work. Some work is mechanical work — moving muscles — but most of the energy is used for chemical: work making body material and keeping biological structures intact and generally keeping things running.  The medium of energy in metabolism is the chemical reaction of synthesis and breakdown of the molecule ATP.  Textbooks frequently refer to ATP as a “high energy molecule” but it is not the compound itself but rather the reaction (synthesis and breakdown (hydrolysis)) that is high energy.  For the moment, we can think of ATP as the “coin of energy exchange in metabolism.”  A heavy-duty thought concept: the challenge for biochemistry historically was to explain how the energy from an oxidation-reduction reaction could be used to carry out the synthesis of ATP which has a different mechanism (phosphate transfer).  The process is called oxidative phosphorylation and was only figured out about fifty years ago.

So again, our two goals in human metabolism: Make energy in the form of ATP and maintain a pretty much constant level of blood glucose for those cells, brain and central nervous system, that require glucose (the brain can’t use fatty acids as a fuel).

Let’s look at energy production first because it is a little easier to understand.  As we look inside the black box, each of the processes uncovered will have its own degree of complexity.  In reading this you have to do what scientists do: hang in there.  Skip over the parts that seem complex and see if you can come back to them later.

The role of redox coenzymes

So, breaking into the black box, the first thing to notice is that the oxidation of food is done in steps, and that there is another player that mediates the process by coupling separate pieces: the food never sees the oxygen.  The intermediaries are called coenzymes or cofactors.  The most important oxidative coenzyme is known as NAD.  It’s always referred to by the acronym, but if you’ve had some organic chemistry and you’re curious, NAD stands for nicotinamide-adenine-dinucleotide; the structure is shown in the figure and the action end of the molecule is indicated. NAD coenzymes are derived from the vitamin niacin.  So   what happens in metabolism is that food is oxidized by NAD+ (the oxidized form of NAD) and the product, NADH (the reduced form) is re-oxidized by molecular oxygen. Although it is still just as we thought (food+oxygen-in, CO2+water-out), the oxygen never sees the food.   Why do we do it this way?  If we did it all in one big blast like an automobile engine, we would have little control over it and we would not be able to capture the energy in a usable chemical form.

It’s easiest to start with glucose, a six-carbon compound. The early steps in metabolism involve a process known as glycolysis (sugar splitting) that ultimately gives you two molecules of a three-carbon compounds known as pyruvic acid. Pyruvic acid is oxidized to a derivative of acetic acid, known as acetyl-CoA. The CoA is short for Coenzyme A, a complicated molecule but, like many coenzymes is always referred to in this way so it is not important to know the detailed structure.  The compound is frequently written acetyl-SCoA to emphasize that it is a thioester (sulfur ester); again, the “S” is not pronounced.

Acetyl-SCoA is the fuel for the major NADH-producing process, known as the Krebs cycle after the major player in its discovery. Without looking into that black box too much the key compound is citric acid, which is, chemically a try-carboxylic acid (TCA) so the Krebs cycle is also called the citric acid cycle or TCA cycle; Krebs called it the TCA cycle so I will generally use that term.  The process whereby NADH is finally re-oxidized by oxygen is known as electron transport.  So, The big black boxes of metabolism:

Where do we get Glucose and Acetyl-CoA?

So far we know: most energy comes from the oxidation of acetyl-CoA and most of the glucose that provides energy does so by first being converted to acetyl-CoA. Where else can we get acetyl-CoA? We’ve taken glucose as synonymous with food but where else can we get glucose from besides the diet?

Looking ahead, the big results that will come out of opening up the black box of metabolism: 1) Acetyl-CoA also comes from fat and to a smaller extent from protein.  2) Glucose can also be formed from protein. 3) Under conditions where there is no dietary glucose (starvation, low carbohydrate diet), glucose will be made from protein or released from stored glycogen, and an alternative fuel ketone bodies will provide acetyl-CoA; ketone bodies are essentially a dimer of acetyl-CoAs and the liver makes and exports ketone bodies to other cells.  Acetyl-CoA and, therefore, glucose can be converted to fat but a major asymmetry that will have profound significance is that 4) glucose cannot be formed from acetyl-CoA.  The significance of the last statement is that: we know all too well that fat can be formed from glucose but, with minor exceptions, 5) glucose cannot be formed from fat. (Chris Masterjohn’s post “We Really Can Make Glucose From Fatty Acids After All!”
indicates the extent to which the exceptions become important but the overriding principle that has the most impact on metabolism is that you cannot make glucose from fat).
So that’s it.  You now have a blackbox view of metabolism.  I will try to open some of the boxes in future posts.

Summary of fuel sources and synthesis and looking ahead.

  1. There are, roughly speaking, two kinds of fuels: glucose and acetyl-CoA.
  2. Carbohydrates and other nutrients, fat (that is, fatty acids) and protein (amino acids) can supply acetyl-CoA.  Glucose is not required for acetyl-CoA and under conditions of low carbohydrate or low total food, fatty acids become the major source of acetyl-CoA.
  3. Not all tissues can use all fuel sources. Brain, CNS and red blood cells, for example cannot use fatty acids. Brain and CNS can use acetyl-CoA but cannot get it from fatty acids.  Red blood cells only use glucose and, to a first approximation, brain and CNS are also dependent on glucose for metabolism.
  4. Under conditions of starvation or carbohydrate restriction, acetyl-CoA can be effectively transported from the liver in the form of  ketone bodies. Ketone bodies, then, are a source of acetyl-CoA that can be used by brain and CNS.  Red blood cells are still dependent on glucose but the brain’s demand for glucose is reduced by the availability of ketone bodies.
  5. There is no dietary requirement for carbohydrate and amino acids can also supply glucose through the process of gluconeogenesis.
  6. Fat as a source of acetyl-CoA also works the other way: acetyl-CoA can be converted to fat.
  7. Whereas glucose can be converted to fat, with a few exceptions, fat cannot be converted to glucose. This will be a key idea behind carbohydrate restriction.
  8. Glucose can also be stored as the polymer glycogen.
  9. Bottom line is the limitation of “you are what you eat.” Metabolism means the interconversion of food and metabolites. Conversely, it will be critical that not everything is interconvertible. In particular, we will emphasize that you can make fat from carbohydrate but, to a large extent,  you cannot make glucose from fat.

Looking ahead on sources of blood glucose:

  1. Glucose from dietary input (referred to as the fed state; in nutrition, as the postprandial period), is depleted after about 8 hours.
  2. Glycogen is a storage/supply source of glucose.  Liver glycogen can supply export glucose to the blood, thereby supplying other tissues.  Muscle glycogen supplies glucose only for the muscle itself.  Glycogen may become largely depleted after 24 hours, depending on the conditions (exercise, for example).
  3. The third source of blood glucose is gluconeogenesis (GNG) which, as the name implies, makes glucose anew from existing metabolites. Depending on the conditions, the source of carbon may be amino acids, lactic acid or glycerol from fat metabolism.  Whereas it is sometimes indicated to be a “last ditch” source of glucose in the textbooks, it goes on all the time. The glucose it synthesizes in GNG may be used to replenish glycogen and only appear in the blood at a later time.

The last Organic-Biochemistry-Nutrition post presented the saturated hydrocarbons, which are familiar as gasolines and other fuels and oils.  The first step in getting control of organic chemistry is to be sure you can identify each compound which means recognizing (or assigning) a precise name.  From a theory standpoint, these compounds also provide the skeletons for nomenclature of the other classes of organic compounds.

The class of alcohols are those compounds that have a saturated carbon backbone and have one or more -OH groups attached.  The simplest alcohol is methanol CH3-OH.  Others are shown in the figure from the last post which emphasized that even if the backbone got very complicated, as in cholesterol, it was still an alcohol. The greater the percentage of the molecule that is -OH rather than hydrocarbon, the more they resemble water and the more they behave like water.  So, methanol, ethanol and propanol are soluble in water whereas butanol and higher alcohols are not.  Looking ahead, however, there are other chemical properties that are common to all alcohols: this is why it is so convenient to lump them together.

I received a comment on the last post that said “One wish, though: I don’t quite understand the graphic on cholesterol and how would that look when presented as the chemical symbols like all the other molecules in that last picture.”  I suggested the following exercise for understanding it by problem-solving. If you want to try this first, here is the exercise (answers follow):

  1. Draw the molecular formula for hexane.
  2. Connect the ends of the molecule by making a carbon-carbon bond.
  3. Recognize that now you have a hexagon-shaped objects all of whose vertices are CH-2. This molecule, not-surprisingly, is called cyclohexane.
  4. Since you know that all the points are CH-2, you can save time by just drawing the geometric figure.
  5. To make sure you have the idea, draw cyclopentane.
  6. Now draw a structure with two fused rings: two hexagons sharing a common side. This structure is called decalin (because it has ten carbons).
  7. Draw a C at each vertex or intersection. Now fill in hydrogens so that every carbon has four bonds. There should be 8 CH-2 and 2 CH.
  8. You can make a complex structure with three fused hexagons and one pentagon, as in the drawing. This structure is called cholestane and is the basis of the cholesterol in the drawing.
  9. If all this makes sense, Google “cholesterol structure” and click on “Image” in the top menu bar and you’ll see different representations.

The arrow is meant to show that the hexane molecule has no rigid structure and could be folded up. The relation to cyclohexane is formal, that is, pictorial.  (It is not that easy to convert one to the other in the laboratory). This has defined a new class of compounds, the cyclic hydrocarbons, that, rather than straight chains, are arranged in cyclic structures.  Before tackling questions 8 and 9, need to look at one more basic step.

Precise Names.

The allure of organic chemistry (to those who are attracted to it) is its precision and logic.  That’s why an important feature is the name game, giving precise names to organic compounds.  The idea is that if you order something from a chemical company, you want to know exactly what you are going to get.  Thinking about butanol, now, you might ask what you would call a compound that had exactly the same composition as butanol except that the -OH group was not at the end but rather attached to one of the other carbons.  To remove ambiguity in a case like this, the carbons are numbered. There are, in fact, two butanols: 1-butanol and 2-butanol.  There is no such thing as 3-butanol because, looking at the structures and remembering that we are trying to represent something from 3-D space, there is no difference between carbon-2 and carbon-3.

The big rule for numbering organic compounds: pick a numbering system that has the lowest numbers.  Even if, for some reason, the structure is written so that the hydroxyl group appears to be at the far end, you always pick the number so that is the lowest possible.  The next figure shows you some examples.  Make sure you are happy with this system.

More on Hydrocarbons.  Branched Chains.

The unique features of carbon atoms: the ability to form four chemical bonds and to form chemical bonds with other carbon atoms to form long chains. In addition to long linear chains, carbon can also form compounds with branches. Once you have 4 carbons in a chain (butane)there is more than one way to arrange the carbons. The figure below shows different representations of a compound called iso-butane, an isomer of what we originally wrote for butane. (Isomers are compounds that have the same type and number of atoms but a different arrangement). The straight chain form could be called normal butane, or n-butane but, once there is a precise name for isobutane, n-butane will just be called butane.

 

So, the problem is that there are literally millions of compounds and you can’t have a name for every one. Besides, chemists don’t really like to memorize things and pretty much feel that learning the names of the ten straight chain hydrocarbons should be enough and there must be a logical system for naming organic compounds by relating them to the simpler ones.

The Systematic Name Game.

The system in organic (called the IUPAC system after the International Union of Pure and Applied Chemists) starts from the straight chain hydrocarbons. Every compound is named as if it were derived from one of those.  To name a compound, then, find the longest possible continuous straight chain of carbon atoms.  For isobutane, this would be 3, that is propane.  What about the extra carbon atom?  That is assumed to come from a hydrocarbon too but is considered a substituent (substituting for a hydrogen atom), that is, an “add-on” and is given an adjective name “methyl,” and so a systematic name for isobutane is methyl-propane.  Similarly, there are two isomers for the 5-carbon hydrocarbon: pentane and methyl-butane.  For the 6-carbon compounds vatiation, methyl-pentane, there are two different isomers. Using the rule from the alcohols, the two must be called 2-methyl pentane (never  4-methylpentane) and 3-methylpentane. The examples at the end of this post should allow you to learn how to play the game.  A couple of questions are included.  Answers will be in the comments and the structures in the next post.  To find out what kind of substance they represent, for the simpler ones like isobutane, you can Google them but you should have a sense of power that you can give the precise chemical name for a large number of chemicals. First, two more rules.

Hydrocarbon names and substituent names.

Substituents can have more than 1 carbon (although obviously not more than the main chain to which they are attached. Why not?)

More than one substituent gets more than one number.

If there is more than one substituent, you use the prefix di-, tri-, tetra-, penta-, hexa- and indicate all numbers, even if they fall on the same carbon.  You should be able to follow the examples and you should be able to do the questions.

External links

For more information or to reinforce what you have here: Drawing organic molecules and Organic structures sites as well as Quiz on naming organic compounds.  Also, good intro as part of heavy-duty organic text (skip parts that are complicated).

Finally, cholestane

The hydrocarbon chains (and branches) can sometimes be written, like the cyclic hydrocarbons, just showing the geometry.  Recall the 3-D convention: a wedge represents atom coming out of the screen and a dotted line, an atom behind the plane of the screen.  Here it is.  Cholestane is the basic structure.  Cholesterol is an alcohol derivative as above.