BCH 203 Intermediary Metabolism (2020-21)

BCH 203
Intermediate metabolism
Intermediary or intermediate metabolism is the subfield of biochemistry traditionally concerned
with the vast and highly integrated network of biochemical reactions that provides cells with
forms of energy for immediate use (i.e., metabolic energy), reducing power and biosynthetic
intermediates.
Metabolism consists of a series of reactions that occur within cells of living organisms to sustain
life. Metabolism can be split into a series of chemical reactions that comprise both the synthesis
and degradation of complex macromolecules known as anabolism or catabolism, respectively.
Metabolism can be divided, for convenience, into anabolism, the enzymatic synthesis of
macromolecules from simple precursors, and catabolism, the degradation of precursor molecules
of either intra- or extracellular origin to simple organic molecules and waste products. Examples
of the former are lipid, protein, and nucleic acid synthesis and of the latter proteolysis,
glycogenolysis, and the energy-producing reactions of glycolysis and the mitochondrial
respiratory chain. Intermediary metabolism encompasses the compounds which are intermediates
in the processes and the regulatory mechanism which maintain their homeostasis. These
reactions serve to ensure there is adequate energy in the form of ATP for production of essential
cell substances (structural macromolecules, enzymes, and neurotransmitters), uninterrupted
operation of essential cell processes (maintenance of ionic concentration gradients), and
elimination of metabolic waste products (ammonia fixation).
The immediate source of energy for most cells is glucose. But glucose is not the only fuel on
which cells depend. Other carbohydrates, fats and proteins may in certain cells or at certain times
be used as a source of ATP. The complexity of the mechanism by which cells use glucose may
make you fervently hope that a similarly-constructed system is not needed for each kind of fuel.
And indeed it is not.
One of the great advantages of the step-by-step oxidation of glucose into CO 2 and H2O is that
several of the intermediate compounds formed in the process link glucose metabolism to the
metabolism of other food molecules.
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Intermediary Metabolism
For example, when fats are used as fuel, the glycerol portion of the molecule is converted
into PGAL and enters the glycolytic pathway at that point. Fatty acids are converted into
molecules of acetyl-CoA and enter the respiratory pathway to be oxidized in the mitochondria.
The amino acids liberated by the hydrolysis of proteins can also serve as fuel.
 First, the nitrogen is removed, a process called deamination.

 The remaining fragments then enter the respiratory pathway at several points.
For examples,
 the amino acids Gly, Ser, Ala, and Cys are converted into pyruvic acid and enter the
mitochondria to be respired.
 acetyl-CoA and several intermediates in the citric acid cycle serve as entry points for
other amino acid fragments (shown in blue).
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These links thus permit the respiration of excess fats and proteins in the diet. No special
mechanism of cellular respiration is needed by those animals that depend largely on ingested fats
(e.g., many birds) or proteins (e.g., carnivores) for their energy supply.
Much of the protein we consume is ultimately converted into glucose (a process called
gluconeogenesis) to provide fuel for the brain and other tissues. Although all our foods are
interconvertible to some extent, they are not completely so. In other words, no single food can
supply all our anabolic needs. We can indeed synthesize many fats from glucose, but certain
unsaturated fats cannot be synthesized and must be taken in directly in our diet. These are
linoleic acid, linolenic acid, and arachidonic acid. All are unsaturated; that is, have double bonds.
Although we can synthesize 11 of the amino acids from carbohydrate precursors, we must obtain
9 others (the "essential amino acids") directly.
Many of the points that connect carbohydrate metabolism to the catabolism of fats and proteins
serve as two-way valves (indicated in the figure by double-headed arrows). They provide points
of entry not only for the catabolism (cellular respiration) of fatty acids, glycerol, and amino
acids, but for their synthesis (anabolism) as well. Thus the catabolic breakdown of starches can
lead (through acetyl-CoA and PGAL) to the synthesis of fat.
Fructose presents a special problem

Fructose is produced by the digestion of the disaccharide sucrose (common table sugar) into the
monosaccharides glucose and fructose. Both glucose and fructose share the same empirical
formula (C6H12O6) and the same caloric content (686 kcal/mole). But the body treats them very
differently.
Glucose is taken up and metabolized by all cells to generate ATP by glycolysis and cellular
respiration, and excess glucose is preferentially converted into glycogen rather than fats.
Fructose is taken up only by liver cells, and excess fructose is converted in fats (fatty acids and
glycerol). In the U.S., most soft drinks and prepared foods are now sweetened with high-fructose
(60% fructose, 40% glucose) corn syrup. Excessive consumption of these products may well be
linked to the growing prevalence in the U.S. of obesity and type 2 diabetes.
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Connection of Carbohydrate, Protein, and lipid metabolism
Connections of Other Sugars to Glucose Metabolism

Glycogen, a polymer of glucose, is an energy storage molecule in animals. When there is
adequate ATP present, excess glucose is shunted into glycogen for storage. Glycogen is made
and stored in both liver and muscle. The glycogen will be hydrolyzed into glucose monomers (G-
1-P) if blood sugar levels drop. The presence of glycogen as a source of glucose allows ATP to
be produced for a longer period of time during exercise. Glycogen is broken down into G-1-P
and converted into G-6-P in both muscle and liver cells, and this product enters the glycolytic
pathway.
Sucrose is a disaccharide with a molecule of glucose and a molecule of fructose bonded together
with a glycosidic linkage. Fructose is one of the three dietary monosaccharides, along with
glucose and galactose (which is part of the milk sugar, the disaccharide lactose), which are
absorbed directly into the bloodstream during digestion. The catabolism of both fructose and
galactose produces the same number of ATP molecules as glucose.
Connections of Proteins to Glucose Metabolism

Proteins are hydrolyzed by a variety of enzymes in cells. Most of the time, the amino acids are
recycled into the synthesis of new proteins. If there are excess amino acids, however, or if the
body is in a state of starvation, some amino acids will be shunted into the pathways of glucose
catabolism. Each amino acid must have its amino group removed prior to entry into these
pathways. The amino group is converted into ammonia. In mammals, the liver synthesizes urea
from two ammonia molecules and a carbon dioxide molecule. Thus, urea is the principal waste
product in mammals produced from the nitrogen originating in amino acids, and it leaves the
body in urine.
Connections of Lipid and Glucose Metabolisms

The lipids that are connected to the glucose pathways are cholesterol and triglycerides.
Cholesterol is a lipid that contributes to cell membrane flexibility and is a precursor of steroid
hormones. The synthesis of cholesterol starts with acetyl groups and proceeds in only one
direction. The process cannot be reversed.
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Triglycerides are a form of long-term energy storage in animals. Triglycerides are made of
glycerol and three fatty acids. Animals can make most of the fatty acids they need. Triglycerides
can be both made and broken down through parts of the glucose catabolism pathways. Glycerol
can be phosphorylated to glycerol-3-phosphate, which continues through glycolysis. Fatty acids
are catabolized in a process called beta-oxidation that takes place in the matrix of the
mitochondria and converts their fatty acid chains into two carbon units of acetyl groups. The
acetyl groups are picked up by CoA to form acetyl CoA that proceeds into the citric acid cycle.

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BCH 203

 First, the nitrogen is removed, a process called deamination.

Fructose presents a special problem

Connections of Other Sugars to Glucose Metabolism

Connections of Proteins to Glucose Metabolism

Connections of Lipid and Glucose Metabolisms

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