Carbohydrate Digestion, Metabolism, and Storage

Carbohydrate Digestion, Metabolism, and Storage

I am not a doctor, and none of this should be construed as medical advice. Every person is different. Please consult your physician before doing any dietary changes.

Carbohydrates are listed, along with protein and fat, as one of the three major “macronutrients.” We will discuss exactly what happens when one eats carbohydrates from the very first bite.1 First, let us look at the nomenclature for the different kinds of carbohydrates.

1 Nomenclature

1.1 Monosaccharides

The simplest type of carbohydrate is the monosaccharide. There are many monosaccharides, but four are important dietarily: glucose,2 fructose, mannose, and galactose. Monosaccharides are the building blocks of all other carbohydrates: Di-, oligo-, and polysaccharides are made up of chains of monosaccharides. If you are interested in the full metabolic pathways involved in the metabolism of these sugars, there is a great diagram on WikiMedia Commons. We will ignore mannose and galactose, because they make up relatively little of dietary consumption and are similar enough to glucose metabolically speaking not to go into.

1.2 Disaccharides

Molecular diagram of sucrose

Sucrose consists of a glucose molecule bound to a fructose molecule. Original image placed in the public domain by its owner, NEUROtiker on WikiMedia Commons.

A disaccharide consists of two monosaccharides chemically bound together. Sucrose (table sugar) is a disaccharide of one fructose and one glucose. Maltose is a disaccharide of two glucoses. Metabolically speaking, the effects of disaccharides aren’t terribly different from the effects of each of the monosaccharide constituents. Often, stomach acid itself is strong enough to split disaccharides into their constituent parts. But enzymes exist in the small intestine and even the saliva to break them apart. In the case of maltose, the enzyme maltase cleaves it into two glucose molecules before the small intestine endothelial cells absorb the glucoses. Similarly, sucrase cleaves sucrose into one glucose and one fructose.

An interesting note: Lactose intolerance is caused by a (usually congenital) lack of the enzyme lactase. The body cannot, in this case, cleave lactose into glucose and galactose. Thus, bacteria in the intestine ferment it instead, causing gas and dietary distress.

1.3 Oligosaccharides and Polysaccharides

Molecular diagram of amylose

Amylose (pictured above) is a constituent of starch. It consists of hundreds of glucose molecules bound together. Original image placed in the public domain by its owner, NEUROtiker on WikiMedia Commons.

Oligo- and polysaccharides are longer chains of monosaccharides. Generally speaking, oligosaccharides have about 7-10 monosaccharides, and polysaccharides are usually much longer (reaching into the hundreds or thousands of individual monosaccharide constituents). Like disaccharides, the small intestine secretes enzymes to break these large molecules down into their constituent parts, if they are absorbed into the body. However, there are some polysaccharides that cannot be broken down by the body. We call undigestible carbohydrates dietary fiber, which comes in two categories—soluble and insoluble fiber—depending on whether they can be dissolved in water.

2 Ingestion and Digestion of Carbohydrates in General

The digestion of carbohydrate begins with chewing. Saliva contains many of the enzymes that the stomach and small intestine use to break down carbohydrate. Digestion then continues in the stomach, which both mechanically and enzymatically works to reduce the mass of food before sending it (now called “chyme”) to the small intestine. The stomach does not have the enzymes to break down carbohydrates, but it can sense their presence and tell the brain about what is coming. You may have said after a satisfying meal that it “hit just right.” This is not too far off from the truth. The stomach, working tandem with the tongue and nose, can link tastes to the actual nutrition content you are receiving.

In the small intestine, however, the real magic happens. The duodenum (the first part of the small intestine) senses food nervously, then signals the pancreas hormonally to secrete pancreatic juice. This juice goes through the pancreatic duct to the duodenum, where it combines with the chyme. Pancreatic juice neutralizes the extremely acidic chyme, and soluble and insoluble fiber can bind together to form a gel, to which some carbohydrates will be bound. The cells of the wall of the small intestine (intestinal epithelial cells or enterocytes) can immediately absorb unbound monosaccharides (assuming they are not bound to fiber, which serves to slow down the absorption process).

Pancreatic juice also contains some of the enzymes necessary for the breakdown of di-, oligo-, and polysaccharides. The enterocytes secrete the remainder of the enzymes necessary. But one way or the other, these enzymes hydrolize (break down with water) the bonds in multi-saccharides, transforming them into monosaccharides that the enterocytes absorb. Note: fiber will determine where in the small intestine this breakdown and absorption happens by binding with hydrogen bonds to the other carbohydrates. For instance, a spoonful of sugar will probably be absorbed just past the duodenum, but the sugar in an apple will be absorbed further on, as it first has to break off of the fiber to which it is bound. The gel formed by soluble and insoluble fiber then enters the large intestine, where intestinal bacteria ferment the soluble fiber into small-chain triglycerides (i.e., fats), which the body can then absorb. That’s right: Certain carbohydrates become fats before they are even absorbed into the body. Insoluble fiber can bulk up the stool and stimulate bowel movements.

The enterocytes, in turn, pass glucose into the blood. The pancreas, seeing a rise in blood glucose concentration, secretes insulin into the blood. Blood insulin essentially tells all cells of the body to store glucose and start building up. It is the primary anabolic (building) hormone of the entire body. Skeletal muscle will respond to insulin by absorbing glucose and building up glycogen, and brain cells (which prefer glucose) will absorb it and begin to produce ATP. But there are two main “clearing houses” for blood glucose: the liver and lipocytes (fat cells). Fructose enters the hepatic portal vein and goes right to the liver.

3 Glucose Metabolism and Glycolysis

The metabolic pathway of glycolysis, in detail.

Original image by Thomas Shafee on WikiMedia Commons, under a Creative Commons Attribution license.

Every cell in the human body can metabolize glucose. Indeed, every eukaryotic cell on the earth can metabolize glucose, and most prokaryotic cells can too. Glucose is the most important energy source on the planet.

In the interior of the cell, several enzymes work together to oxidize glucose into pyruvate, a process called glycolysis. The cell can then decarboxylate pyruvate into acetyl-CoA, which enters the citric acid cycle. The cell can use all of the intermediates of glycolysis and none of them are toxic or harmful. Reactive oxygen species (“oxidants”) aren’t created, and the body handles this very well. Glucose can also be used as a building block or converted into other monosaccharides to build the things it needs.

Two salient disorders of glucose metabolism occur. In type-1 diabetes, the pancreas cannot secrete sufficient insulin (or sometimes any insulin at all) to control blood glucose. In type-2 diabetes, the liver and fat cells become “insulin resistant.” They do not respond to insulin to uptake enough glucose to adequately control blood glucose concentrations. This makes the pacreas work harder and hard to produce more insulin. In extremely late-stage type-2 diabetes, the pancreas can become so damaged that it cannot produce sufficient insulin at all. One sometimes hears “insulin resistance” as a subclinical variety of this where the cells are beginning not to respond as quickly or as well to insulin as they ought, but it doesn’t rise to the level of a metabolic disorder like diabetes.

3.1 The Pentose Phosphate Pathway

Diagram of the pentose-phosphate pathway

Original image by user GdenBesten on Wikimedia Commons, licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

The Pentose Phosphate Pathway is an alternative to glycolysis. It also oxidizes glucose, but with a curious effect: Its products are not (for the most part) useful for energy. This pathway can make ribose, a necessary part of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid). It can also make erythrose 4-phosphate, which makes some types of amino acids. Glycolysis is, in general, preferred to the pentose phosphate pathway. The pentose phosphate pathway mostly only occurs in the liver. NADP+ weakly stimulates the enzyme regualting the pathway, and NADPH strongly inhibits the pathway. And in the liver, NADPH vastly outnumbers NADP+. I show this pathway for completeness. Glucose is not only used for its energy, but that is its primary purpose.

4 Fructose Metabolism

Diagram of the fructose metabolic pathway

Original image from user Clariebh on the English Wikipedia, licensed under CC Attribution-Sharealike

Several kinds of tissue can metabolize fructose, but for the most part, fructose breakdown occurs in the liver. The liver can convert it into glucose, add it to its store of hepatic glycogen, or convert it to triglycerides. Dr. Robert Lustig, among others, has fingered these last two systems as being partially or even mostly responsible for non-alcoholic fatty liver disease and metabolic syndrome.

In particular, Dr. Lustig has likened fructose to alcohol, with its toxic side-products and contribution to fatty liver. Indeed, alcohol catabolism produces acetaldehyde, and fructose catabolism produces glyceraldehyde, a similar molecule. They both can damage the cell through the creation of reactive oxygen species.3 He gave an interesting talk about the phenomenon of fructose and NAFLD, a follow-up to a former talk on the same subject that went somewhat viral. I think he overstates the effect of fructose (and understates the effect of glucose, starch, and insulin resistance); nevertheless, he is the pediatric endocrinologist, and I am just a schmuck.

5 Insulin

Lipocytes (fat cells), liver tissue, and muscle tissue absorb more blood glucose in response to rising insulin levels. Furthermore, insulin discourages autophagy—the process whereby dysfunctional cells and organelles are broken down—and discourages the breakdown of protein—in fact, insulin encourages cells to absorb more amino acids and synthesize new proteins. This is why insulin is the primary anabolic hormone of the body. It promotes protein synthesis and demotes catabolism of what has already been made. It even promotes DNA and RNA synthesis and thus cell division. This is a very good thing, when it is necessary. Adolescents and pregnant women cultivate some amount of insulin resistance in order to stimulate the production of more insulin and build muscle, fat, and other tissue.

5.1 The Liver

In response to rising insulin, the liver, in addition to absorbing more glucose and manufacturing protein, does several things to both control blood glucose levels and stimulate the production of new tissue: The liver deposits glucose as glycogen (glycogenesis), and it slows the endogenous production of new glucose (gluconeogenesis) and hydrolization of glycogen to glucose (glycogenolysis). The liver will also absorbs more potassium to compensate for the amount of water that the new glycogen needs.

It is also instructive to look at what happens when insulin levels are low. The body needs blood glucose—no ifs, ands, or buts about it. The brain cannot catabolize fatty acids or proteins for energy, and about 25% of nervous system tissue is completely dependent on glucose. It cannot use any other fuel whatsoever. In response to low blood glucose levels, the pancreas ceases to secrete so much insulin. This allows other cells in the pancreas to release the hormone glucagon—a kind of inverse to insulin, which basically has the exact opposite effects of insulin: Less new glycogen is made and existing glycogen is broken down and released to the blood stream. The liver begins to create new glucose cells de novo and releases potassium to compensate for the efllux of water with the glycogen. Autophagy and protein breakdown are somewhat encouraged so the body has more substrate to survive.4

5.1.1 Glycogen

Image of glycogen

An image of glycogen. Original image by Mikael Häggströmon on WikiMedia Commons, into the public domain.

Glycogen is a polysaccharide that is synthesized within the body. Two places store glycogen: skeletal muscle and the liver. In skeletal muscle, glycogen is saved for a “rainy day,” when the muscle is stressed and cannot get enough blood glucose for the energy it needs. The muscle simply breaks down its glycogen stores and uses that. However, the muscle cannot export glucose to the blood. Once it’s in, it’s in. The liver, however, stores a great deal of glycogen for the entire body, usually about 100-120g, or about 375-425kcal of energy. It’s a good deal of energy. In the fasted state, it will be called upon by the brain, which needs glucose to survive. Glycogen can buy a human another few days of complete fasting. (Remember, other tissues can use fats and proteins for fuel directly, so it’s mainly nervous tissue that needs glycogen). Past that, we would need to rely on fat stores to weather several days of starvation.

Glycogen is a very “wet” molecule—it requires a lot of intracellular water to keep it bound and to regulate its molality. In fact, each gram of glycogen travels with about 2-4g of water. So when you hear about people losing “water weight” (or if you’ve noticed you urinate a lot after about a day or so of fasting), it is normally from the breakdown of glycogen. Each time you lose a gram of glycogen, you must lose 2-4g of water. This is also why the liver must take up more potassium ions when producing glycogen. With the excess water, potassium is required to maintain homeostasis. Glycogen’s hydrophilia also causes electrolyte loss during diet and fasting; the electrolytes are being shed with the water.

5.2 The Fat Cell

Three fatty acids bound to a glycerol background

A molecule of triglyceride. Notice how the three fatty acids (the long chains on the right) are connected to the glycerol backbone (on the left). Original image by Instituto de Energías Renovables - UNAM / CC BY-SA

The lipocyte also responds potently to insulin. The storage form of fatty acids in humans is a triglyceride—three fatty acid chains attached to a glycerol backbone. The complete process of fatty acid metabolism is for another article, but in the broad strokes, insulin encourages fat cells to hold onto their fat and even to produce new fat (de novo lipogenesis) from blood glucose. In response to glucagon, the fat cell does the opposite: It de-esterifies the fatty acids (removes them from their glycogen backbone) and sends those to the bloodstream, slows the intake of glucose, and slows the production of new triglycerides.

6 Pulling It All Together: The Glycemic Index

One interesting metric to look at is how much a particular carbohydrate raises blood sugar. The glycemic index of food gives us insight into this. Pure glucose has a glycemic index of 100. Fructose actually only has a glycemic index of 19 (meaning that in equal amounts it would only raise blood sugar about 19% of glucose). Maltose (two glucoses together) has a glycemic index of 104, meaning it raises blood sugar even more than pure glucose! Dietary fiber generally has a glycemic index of 0. It does not raise blood sugar measurably and may even slow the action of other foods on blood glucose. Paying attention to how much food one is eating that raises blood sugar appreciably may be important for the insulin resistant.



Sometimes you see carbohydrate in the singular as a mass noun like “food,” but most persons use it in the plural.


Glucose is also known as dextrose when derived from corn.


A partial lack of the enzyme acetaldehyde dehydrogenase prevents the complete breakdown of acetaldehyde and thus causes “asian glow,” wherein some persons go flush after consumption of alcohol. Acetaldehyde is also responsible for some of the intoxicating effects of alcohol. (N.B.—Ethanol itself can cross the blood-brain barrier and is responsible for most of the intoxicatory effects.) The reason fructose does not intoxicate one is that it does not enter into the brain at all, and neither does glyceraldehyde.


One might wonder at this juncture, as I did, whether there is an analogue to insulin resistance for glucagon—a kind of “glucagon resistance.” Well, the evidence is mixed to say the least. An article in the Internation Journal of Molecular Sciences proposes a mechanism for glucagon resistance. (You should read the entire article. It goes over glucagon’s functions and is well-written and fascinating.) But evidence for its existence in humans is close to non-existent. Evidence for hepatic glucagon resistance in rats shows it may come about because of fatty liver disease. However, the mechanisms responsible for FLD in rats and humans differ considerably. In humans, an easier way of inducing fatty liver is actually a high carbohydrate diet, not a high-fat diet, as for rats. In fact, after eating a low-carb diet for a long period of time, humans seem to develop another kind of insulin resistance, so-called “physiologic insulin resistance.” It serves as a protective mechanism to ensure that any blood glucose that is around after a period of deprivation goes to the brain where it is needed and not to other tissue.