Fates of dietary glucose

The major source of dietary carbohydrate for humans is starch from

consumed plant material. This is supplemented with a small amount
ofglycogen from animal tissue, disaccharides such as sucrose from
products containing refined sugar and lactose in milk.
Digestion in the gut converts all carbohydrate to monosaccharides
which are transported to the liver and converted to glucose. The liver
has a central role in the storage and distribution within the body of all
fuels, including glucose.
Glucose in the body undergoes one of three metabolic fates :

• it is catabolised to produce ATP

This occurs in all peripheral tissues, particularly in brain,

muscle and kidney.

• it is stored as glycogen

This storage occurs in liver and muscle.

• it is converted to fatty acids

Once converted to fatty acids, these are stored in adipose

tissue as triglycerides.
Glucose catabolism
Glucose will be oxidised by all tissues to synthesise ATP. The first
pathway which begins the complete oxidation of glucose is
calledglycolysis.
Glycolysis
This pathway cleaves the six carbon glucose molecule (C6H12O6) into two
molecules of the three carbon compound pyruvate (C3H3O3-). This
oxidation is coupled to the nett production of two molecules of
ATP/glucose.
The diagram below shows an outline of glycolysis. The full set of
reactions and structures can be found in any biochemistry textbook.
One oxidation reaction occurs in the latter part of the pathway. It uses
NAD as the electron acceptor. This cofactor is present only in limited
amounts and once reduced to NADH, as in this reaction, it must be re-
oxidised to NAD to permit continuation of the pathway.
One oxidation reaction occurs in the latter part of the pathway. It uses
NAD as the electron acceptor. This cofactor is present only in limited
amounts and once reduced to NADH, as in this reaction, it must be re-
oxidised to NAD to permit continuation of the pathway.
This re-oxidation occurs by one of two methods :

Anaerobic glycolysis

• pyruvate is reduced to a compound called lactate

This single reaction occurs in the absence of oxygen

(anaerobically) and is ideally suited to utilisation in heavily
exercising muscle where oxygen supply is often insufficient to
meet the demands of aerobic metabolism. The reduction of
 pyruvate to lactate is coupled to the oxidation of NADH to NAD.

Aerobic metabolism of glucose

• pyruvate is transported inside mitochondria and oxidised to a

compound called acetyl coenzyme A (abbreviated to "acetyl
CoA").

This is an oxidation reaction and uses NAD as an electron

acceptor.
By a further series of reactions collectively called the citric acid cycle,
acetyl CoA is oxidised ultimately to CO2. These reactions are coupled to
a process known as the electron transport chain which has the role of
harnessing chemical bond energy from a series of oxidation/reduction
reactions to the synthesis of ATP and simultaneously re-oxidising NADH
to NAD. (These pathways will be discussed in more detail later.)
Fast twitch muscle fibres utilise the first of the two mechanisms
described above almost exclusively. Very heavily exercising muscle can
use this pathway as the sole source of ATP synthesis for a short period
of time. This probably evolved in humans as a defence mechanism, but
is now used by athletes in sprint events.
The formation of lactate as an end product from glucose extracts only a
relatively small amount of the bond energy contained in glucose.
Accumulation of lactate (actually lactic acid) also causes a reduction in
intracellular pH.
The lactate formed is removed to other tissues and dealt with by one of
two mechanisms :

• it is converted back to pyruvate

The pyruvate then proceeds to be further oxidised by the second

mechanism described above, finally producing a large amount of
ATP.

• it is converted back to glucose in the liver

Gluconeogenesis
The process of conversion of lactate to glucose is
called gluconeogenesis, uses some of the reactions of glycolysis (but in
the reverse direction) and some reactions unique to this pathway to re-
synthesise glucose. This pathway requires an energy input (as ATP) but
has the role of maintaining a circulating glucose concentration in the
bloodstream (even in the absence of dietary supply) and also
maintaining a glucose supply to fast twitch muscle fibres.

Cori cycle
It can be shown by a complex calculation of energy yields that this
process of partially oxidising glucose to lactate in muscle, transporting it
to the liver for conversion back to glucose and then re-supplying it to
muscle, actually has a much higher energy yield than the 2 ATP/glucose
produced by glycolysis alone. This co-operative cycle utilising both the
muscle and liver tissue is called the Cori cycle. The process is shown in
a diagram below.

Both of these mechanisms illustrate the interdependence of tissues on

each other and the co-operative activities between organs which make
 up the total of the body's metabolic activities.

Glycogen and glucose interconversion

Glycogen is a highly branched polymer of glucose. The high degree
of branching (about every twelve glucose residues) produces a
molecule which is compact and thus can be efficiently stored in the
limited space available in liver and muscle tissue.
Even though the branching is designed to make the molecule
compact, it is still a polar molecule and thus must be stored with
associated water. It is stored as aggregates of glycogen molecules
within cells (visible microscopically as glycogen granules) with up to
70% of the aggregate being water.

Glycogen stores
Organ mass Glycogen (g/kg tissue) Total glucose
Liver 1.6 kg 65 ~100 g
Muscle 28 kg 14 ~400 g

The amount of glycogen in muscle changes substantially between

the fed state and following heavy exercise. The amount of glycogen
stored in the liver is more constant and only falls substantially after
prolonged starvation.
In both muscle and liver there is interconversion between the
monomer glucose and the polymer glycogen. This has the potential
to be a futile cycle wasting energy if the interconversion occurred
continuously; thus it is controlled to meet the body's glucose
requirements at a particular time.

Hormonal control of glycogen metabolism

The control which operates is via different enzymes catalysing the
synthesis and breakdown (degradation) of glycogen. The activity of
these enzymes is controlled such that only one is active at any one
time and thus the pathway can proceed in only one direction - either
towards glycogen synthesis OR towards glycogen breakdown and
mobilisation of free glucose.
The control is exerted by hormones acting to control the activity of the
key enzymes. There are some differences in the hormone action in
liver and muscle.
HORMONE Source Target tissue Action
Glucagon Pancreas Liver Stimulates glycogen breakdown
Adrenaline Adrenals Muscle Stimulates glycogen breakdown
Insulin Pancreas Liver and Muscle Stimulates glycogen synthesis

Utilisation of glucose in the fed and fasting states

Glucose utilisation after a meal

A high circulating glucose concentration is present after a meal.
Carbohydrate is digested and the glucose absorbed into the blood
stream. Insulin is secreted in response.
Insulin :

• stimulates uptake of glucose into both muscle and liver

• stimulates increased glycogen synthesis in both muscle and

liver
This is achieved by activation of the key synthesis enzymes.

The amount of glycogen which can be stored in these two tissues is

limited and once the stores are saturated, excess glucose will be
diverted to the synthesis of fats - this will be discussed later.

Maintenance of blood glucose between meals

When there is no dietary glucose intake (between meals), circulating
glucose concentration must be maintained.
The pancreas secretes more glucagon and less insulin.
The glucagon :

• stops liver glycogen synthesis (by deactivating the synthesis

enzymes)
• increases liver glycogen breakdown (by activating the
degradation enzymes)

• stimulates gluconeogenesis in the liver to further increase the

circulating blood glucose concentration
 These mechanisms maintain an appropriate circulating blood
glucose to supply tissues such as the brain which are major glucose
consumers but do not store glycogen.

Supply of glucose to exercising muscle

Increasing muscle activity requires adequate fuel supply

for ATP synthesis by muscle.
When muscle activity is anticipated, the adrenal glands secrete
adrenaline.
Adrenaline increases muscle glycogen degradation (by activating the
breakdown enzymes and de-activating the synthesis enzymes).
When muscle activity ceases, adrenaline secretion is switched off.
When glucose becomes available again after a meal glycogen stores
in muscle are replenished. Glucose can only be supplied to muscle
cells either by utilising stored muscle glycogen or supply from the
liver via the bloodstream.
Muscle does not carry out gluconeogenesis.
Glycogen metabolism in liver and muscle
Energy yield from glycogen breakdown
The energy yield from the hydrolysis of stored glycogen and the
subsequent oxidation of the released glucose is the same in muscle
and liver.
When glycogen is hydrolysed, the product is glucose 1-phosphate.
This is easily converted to glucose 6-phosphate (these are molecules
with the phosphate group attached to different carbon atoms on the
glucose). Glucose 6-phosphate is the first product in the glycolysis
pathway and its formation from glucose requires the expenditure of 1
ATP molecule/glucose.
As glucose 6-phosphate is formed directly from glycogen hydrolysis,
glucose that is derived from glycogen and enters the glycolysis
pathway (rather than starting as monomeric glucose) yields a nett
production of 3 ATP/glucose rather than just 2. This is a 50%
increase in yield.

Role of glucose 6-phosphatase

Muscle and liver have different metabolic needs. Liver supplies other
organs with glucose so must be able to export glucose released from
glycogen hydrolysis. Muscle is a major consumer of glucose and thus
does not export glucose.
 Glucose 6-phosphate formed as described in the previous section is
highly polar and cannot cross the cell's cytoplasmic membrane. To
leave the cell it must be converted to glucose. This reaction is
catalysed by an enzyme, glucose 6-phosphatase.
glucose 6-phosphate →glucose + phosphate
glucose 6-phosphatase
Liver possesses this enzyme, so glucose released from liver
glycogen can be exported to other tissues.
It is very important to be aware that muscle does not possess
glucose 6-phosphatase so it does not export glucose released from
its glycogen stores, but rather uses it as a fuel to power muscle
contraction.
Conversion of excess glucose to fat
Sustained high glucose intake in the diet leads to increased fat
synthesis.
If glucose intake continues after muscle and liver glycogen stores are
saturated, the glucose is not excreted or wasted. It is converted to a
fuel storage form which has an unlimited capacity
i.e. triglycerides stored in adipose tissue.
Glucose is converted to pyruvate by glycolysis. The pyruvate is
converted to acetyl CoA, which is the starting material for the
synthesis of fatty acids. This synthesis occurs in the liver followed by
conversion of the fatty acids to triglycerides (also in the liver) and
then transport to adipose tissue for storage. Triglycerides (fat) form
the major energy store in the body. The mechanism of fatty acid
synthesis will be discussed under the heading of fat metabolism.
Summary of carbohydrate metabolism
The pathways used in carbohydrate metabolism are shown in the following
diagram.
CARBOHYDRATES. Plants manufacture and store carbohydrates as their main source of energy through

photosynthesis. Once consumed, these organic compounds can be digested, absorbed, and metabolized,

supplying humans or animals with energy. Carbohydrates provide roughly half of the total caloric intake of the

average human diet. These calories may be used immediately for energy metabolism or may be transformed and

stored as glycogen or fat to be used as an energy source as demanded. Dietary carbohydrates are comprised of a
wide array of compounds ranging from the simple oneor two-unit sugars to the long chain starches, glycogen and

cellulose. Carbohydrates can be classified as monosaccharides, di-and oligosaccharides, and polysaccharides.

Carbohydrate classification

Classification Number of sugar units** Examples

Monosaccharides 1 Glucose, galactose, fructose

Disaccharides 2 Sucrose, lactose, maltose

Oligosaccharides 2–10 Includes the disaccharides

Polysaccharides > 10 Glycogen, starch, cellulose

**A "sugar unit" is one monosaccharide—each unit is not necessarily the same monosaccharide. For example, sucrose consists of

one glucose uni and one fructose unit.

Monosaccharides, often referred to as simple sugars, are the simplest form of carbohydrates and are seldom

found free in nature. The three that can be absorbed by the human body include glucose, galactose, and

fructose. Glucose is the most abundant of the monosaccharides and the most important nutritionally. It is the

repeating monosaccharide unit in starch, glycogen, and cellulose, and is found in all edible disaccharides.

Oligosaccharides are short chains of monosaccharide units that are joined by glycosidic bonds. They generally

have between two to ten units, with the disaccharides, those chains containing two units, being the most

abundant. The most common disaccharides include:

Sucrose (from table, cane, and beet sugars), consisting of glucose and fructose

Lactose (from milk sugar), consisting of glucose and galactose

Maltose (from malt sugar), consisting of two glucose units

Polysaccharides are long chains of monosaccharide units. The major polysaccharides include the digestible forms

(glycogen and starch) and nondigestible forms (cellulose, hemicellulose, lignin, pectin, and gums).
Starch is the most common digestible polysaccharide found in plants. It can be found in two forms—amylose and

amylopectin. Amylose is a linear, unbranched molecule that is bound solely by a-1,4 glycosidic bonds.

Amylopectin, which makes up the greatest percent of the total starch content, is branched with a-1,6 bonds at

the branch points.

Glycogen is the major storage form of carbohydrates in animals, found primarily in the liver and skeletal muscle.

When energy intake exceeds energy expenditure, excess calories from fat, protein, and carbohydrate can be used

to form glycogen. It is made up of repeating glucose units and is highly branched. During times of fasting or in

between meals, these chains can be broken down to single glucose units and used as an energy source for the

body. Although found in animal tissue, animal products do not contain large amounts of glycogen because it is

depleted at the time of slaughter due to stress hormones.

Cellulose is the major component of cell walls in plants. Just as starch and glycogen, it too is made up of

repeating glucose molecules. However, the glycosidic bonds connecting the units are b-1,4. These bonds are

resistant to mammalian digestive enzymes rendering cellulose, and other substances containing these bonds,

indigestible. Thus, cellulose is not considered to be a significant source of energy for the body. However, as a

fiber, it is important for intestinal bacteria.

Since cellulose is a major part of the plant cell wall, it also encases some of the starch, preventing the digestive

enzymes from reaching it and decreasing the digestibility of some raw foods such as potatoes and grains.

Cooking causes the granules to swell and also softens and ruptures the cellulose wall, allowing the starch to be

digested.

Dietary Fiber

Fiber can be classified as soluble and insoluble. Soluble fiber, which includes pectin and gums, dissolves in water

to form a gel in the digestive tract. This increases the time the food is in the small intestine, thus increasing the

chance of nutrients being absorbed. It is believed that soluble fiber plays a role in lowering blood LDL cholesterol.

This could be due to the binding and increased excretion of fat and bile acid (a derivative of cholesterol) or other

mechanisms not yet understood. Bacteria in the bowel can use fiber as a food source. These bacteria can degrade

the fiber and release some components that can then be absorbed and used by the body. The increased nutrition

for the bacteria can increase microbial growth, which can then lead to increased stool bulk, with little of the fiber

actually found in the stool.

Insoluble fiber, including cellulose, hemicellulose, and lignin (a noncarbohydrate component of the cell wall that is

often included as dietary fiber), absorbs water, thereby increasing the bulk and volume of the stool. It helps to

speed the movement through the intestinal tract, preventing constipation, and is prescribed in the treatment of
irritable bowel syndrome. It has also been shown that insoluble fibers bind fat-soluble carcinogens and remove

them from the gastrointestinal tract, helping to decrease cancer risk.

Refined and processed foods have not only most of the fiber removed, but along with it many of the vitamins,

minerals, and phytochemicals (chemicals found in plants believed to contain protective properties) that contribute

to the health benefits of whole grain foods. The federal government's Dietary Guidelines for Americans encourage

individuals to include whole grain foods in their diet to ensure adequate fiber to promote proper bowel function,

as well as to receive other added health benefits.

Digestion, Absorption, and Transportation

In order for carbohydrates to be absorbed by the intestinal mucosal cells, they must first be converted into

monosaccharides. The digestive process begins in the mouth with salivary a-amylase that partially breaks down

starch by hydrolyzing some of the a-1,4 bonds. However, the digestion that takes place here is of little

significance since food remains in the mouth for only a brief period, although this may differ depending on

chewing time. The enzyme continues to work for a short time in the stomach until the pH is lowered due to

hydrochloric acid that inhibits the enzyme.

Examples of carbohydrate food sources

Monosaccharides

Glucose Fructose Galactose

Fruit High-fructose corn syrup Milk

Vegetables Honey Milk products

Honey Fruit

Disaccharides

Sucrose Lactose Maltose

Table sugar Milk Beer

 Examples of carbohydrate food sources

Monosaccharides

Glucose Fructose Galactose

Maple sugar Milk products Malt liquor

Fruit

Vegetables

Honey

Polysaccharides

Starch (rye, oats, wheat, rice, potatoes, legumes, cereals, bread)

Dietary Fiber

Soluble

Pectin Gums

Fruits (apples, berries) Oats, barley

Jams and jellies (additive) Ice cream (additive) Legumes

Insoluble

Cellulose Hemicellulose Lignin

Whole wheat foods Whole grains Fruit

Bran Seeds
 Examples of carbohydrate food sources

Monosaccharides

Glucose Fructose Galactose

Leafy vegetables Bran, wheat Vegetables

The bulk of carbohydrate digestion occurs in the small intestine by pancreatic a-amylase. The pH of the small

intestines is increased due to the addition of bicarbonate and bile, allowing the enzyme activity to occur. Specific

disaccharidases located on the intestinal mucosal cells help to further break down the carbohydrates into the

monosaccharides: glucose, fructose, and galactose.

Once the carbohydrates have been broken down, the monosaccharides can be absorbed by the mucosal cells.

Glucose and galactose enter by active transport, which requires energy as well as specific receptors and carriers.

Fructose is absorbed by facilitated diffusion. Like active transport, facilitated diffusion requires a specific carrier,

but instead of needing energy, it relies on the low levels of fructose inside the cell to "pull" the fructose inside.

Once transported through the intestinal wall, the monosaccharides enter the blood through the capillaries and are

carried to the portal circulation and then to the liver.

Metabolism of Carbohydrates

The liver is the major site of galactose and fructose metabolism, where they are taken up, converted to glucose

derivatives, and either stored as liver glycogen or used for energy immediately when needed. Although glucose is

metabolized extensively in the liver, unlike galactose and fructose, it is also passed into the blood supply to be

used by other tissues. Tissues like skeletal muscle and adipose tissue depend on insulin for glucose uptake,

whereas the brain and liver do not. This dependence on insulin becomes a problem for diabetics who either

cannot make insulin (IDDM) or are resistent to insulin (NIDDM). For individuals left untreated, dietary

carbohydrates cause glucose levels to rise, resulting in hyperglycemia, which will lead to serious consequences if

steps are not taken to correct it.

Once in the tissues, the fate of glucose depends on the energy demands of the body. Glucose can be metabolized

through the glycolysis pathway to pyruvate where it is either converted to lactate or completely oxidized to CO2,

H2O, and energy. Liver and skeletal muscle can convert excess glucose to glycogen through a pathway known as

glycogenesis. The glycogen is stored after meals to be used as an energy source when energy demands are

higher than intake. At this time the glycogen is broken down into individual glucose units, a process known as
glycogenolysis, and the glucose can be metabolized further. Excess carbohydrates also can be used as a

substrate for fat synthesis.

Carbohydrates are an essential part of a healthy diet. They provide an easily available energy source, are an

important vehicle for micronutrients and phytochemicals, help to maintain adequate blood glucose, and are

important in maintaining the integrity and function of the gastrointestinal tract. Table 2 contains examples of

foods that contain the various types of carbohydrates.

See also Digestion; Fiber, Dietary; Starch.

BIBLIOGRAPHY

Ettinger, Susan. "Macronutrients: Carbohydrates, Proteins and Lipids." In Krause's Food, Nutrition, and Diet

Therapy, edited Kathleen L. Mahan and Sylvia Escott-Stump. 10th ed. Philadelphia, Pa.: W. B. Saunders, 2000.

FAO/WHO. Carbohydrates in Human Nutrition: Report of a Joint FAO/WHO Expert Consultation, Rome, 14–18

April 1997. Rome: World Health Organization, Food and Agriculture Organization of the United Nations, 1998.

Guthrie, Joanne, and Joan Morton. "Food Sources of Added Sweetners in the Diets of Americans." Journal of the

American Dietetic Association 100 (2000): 43–48, 51.

Kiens, B., and E. A. Richter. "Types of Carbohydrates in an Ordinary Diet Affect Insulin Action and Muscle

Substrates in Humans." American Journal of Clinical Nutrition. 63 (1996): 47–53.

Macdonald, I. A. "Carbohydrate as a Nutrient in Adults: Range of Acceptable Intakes."European Journal of Clinical

Nutrition. 53 (1999): S101–S106.

Debra Coward McKenzie Rachel K. Johnson

STARCH

Starch from plants makes up about half of our dietary carbohydrates. Starch molecules can aggregate to form granules that differ

by size and shape depending on the source of the starch, for example, corn, potato, and manioc. Although there is no difference in

the nutritional value between the starches since all cooked starches are broken down in the body into glucose molecules, they do

differ by characteristics such as solubility, flavor, and thickening power. Because of these characteristics, starch is often removed

from the source to use commercially. For example, the starch can be removed from tubers such as potatoes and manioc (also

known as cassava) through a wet milling process, or in the case of manioc, through leaching and drying. The potato starch is often

used as a thickener or instead of cornstarch in recipes, while manioc is best known as tapioca