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BIOCHEMISTRY 101
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In this topic, you’ll learn some basics of biochemistry; the science of chemical
processes in organisms. You don’t have to memorize all the terminology or be able to
write down the metabolic pathway graphs by heart. Rather, this topic is primarily
intended to give you an objective frame of reference that helps you understand the
more practical topics in the rest of the course. As long as you understand the take-
home messages, you’re fine. This is difficult reading for some and you really won’t
need much of it in practice. You just need to have read it and understood it once and
remember the take-home messages.

All matter is composed of particles. One of the most fundamental classes of chemical
elements a nutritionist needs to be aware of is the macronutrient groups.
Macronutrients are components of food that organisms need to function (nutrients) and
are consumed in large quantities (macro). There are 3 important macronutrients:
• Carbohydrates
• Protein
• Fat

One thing that all 3 nutrients have in common is that their molecular structures are
based on a carbon skeleton, several carbons that are interconnected to form a carbon
chain.

Carbohydrates
As the name suggests, carbohydrates are hydrated carbons; carbons (C) with water
(H20) attached to them. The most basic form of carbohydrate is glucose.
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The molecular structure of glucose

Carbon is black yet sugar is white. To realize that white sugar consists of black carbon,
see what happens when you dehydrate sugar: watch this video.

Protein
A protein molecule is a long chain of amino acids (= polypeptide) that folds to give a 3-
dimensional structure. Amino acid molecules are connected to each other via peptide
bonds. Each amino acid consists of a carbon chain (α-carbon and the side chain) that
carries an amino group and an acid group. (The exception to this is the amino acid
glycine, which only contains the α-carbon and no side chain.)

Fat
Fatty acids consist of long carbon chains with an acid group (carboxyl group).
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Knowing that all the 3 macronutrients are built off of carbon chains is crucial to
understand the main principles of human metabolism.

Energy production
1. The human body oxidizes (‘burns’) carbon chains to gain energy. For this reason,
we can gain energy from carbohydrates, protein and fat.
2. The breakdown products (metabolites) of carbohydrates, protein and fat can be
transferred into each other. This connects metabolic pathways and allows the
body to transform one nutrient class into another, such as storing carbohydrates
as fat in an energy surplus or making glucose out of the carbon skeletons of
amino acids when no glucose is ingested.

Here is a schematic diagram of a connection between different metabolic pathways,

showing how the body can create energy (directly or indirectly) from all 3
macronutrients.
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Getting fat

After you eat carbs (e.g. glucose), each glucose molecule is broken down into smaller
molecules in a process called glycolysis. The product of glycolysis is pyruvate.

Glucose → pyruvate
𝑔𝑙𝑦𝑐𝑜𝑙𝑦𝑠𝑖𝑠

Under aerobic (oxygen containing) conditions, pyruvate is used for acetyl-CoA

production. Acetyl-CoA is also a metabolite of amino acids and a metabolite of fatty
acids.

Acetyl-CoA can be oxidized to CO2 to produce energy; it can also be used for fatty acid
synthesis. Carbohydrates and protein can be transformed into fatty acids and stored as
fat, since acetyl-CoA connects the 3 nutrient pathways.
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Glucose production

Another metabolic fate of pyruvate is transformation into oxaloacetate, which in turn

can be ‘retransformed’ into glucose in a process called gluconeogenesis.

Some amino acids can also be transformed into pyruvate or oxaloacetate and thus be
used for glucose production. Even without any carbohydrate supply from the diet, the
human body can still produce glucose, which can be used to refill glycogen stores.

Take-home messages

Because all 3 major macronutrients contain a carbon skeleton and their breakdown
pathways are connected over 3 molecules (pyruvate, acetyl-CoA and oxaloacetate):

• All macronutrients can be transformed into fat.

• The human body can synthesize glucose without carbohydrate in the diet.
• The human body can use all 3 macronutrients for energy production by breaking
down the carbon chains and oxidizing them to CO2.
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Zooming in on metabolic pathways

Here we go into more detail than you need to remember for specific metabolic
pathways that are used for energy production. As long as you understand the take-
home messages and the image below when you’re done reading, you’re fine.

Many of these metabolic pathways have the function of harvesting energy from your
food’s macronutrients and discarding the waste products via your lungs or urine.
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Glycolysis

Glycolysis is a simple metabolic pathway via which your body produces energy from
the carbohydrate in your food. Specifically, glycolysis is the pathway by which glucose
is degraded into 2 3-carbon units (2 pyruvate molecules). Glycolysis can function under
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either aerobic (oxygen being available) or anaerobic (oxygen not being available)
conditions.

In anaerobic conditions or when cellular metabolism is high, pyruvate is converted to

lactate. The conversion to lactate occurs mainly in times of strenuous exercise when
the demand for oxygen by the working muscles exceeds what is available. Under these
anaerobic conditions, glycolysis releases a small amount of usable energy (ATP
molecules) that can help sustain the muscles even in a state of oxygen debt. The major
function of the anaerobic pathway of glucose to lactate is to provide this energy.

Lactate produced under anaerobic conditions can also diffuse from the muscle to the
bloodstream and be carried to the liver for conversion to glucose. This will be described
in detail later.

Under aerobic conditions, pyruvate can participate in the TCA cycle, where it is
completely oxidized to CO2 (most of which we exhale through our lungs) and H2O (H2O
is formed out of the oxygen we breathe in). Complete oxidation is accompanied by the
release of relatively large amounts of energy, much of which is salvaged as ATP by the
mechanism of oxidative phosphorylation (described later).

Take-home message: Glycolysis is a metabolic pathway by which your body produces

energy from the carbohydrate in your food. Glycolysis degrades glucose into pyruvate
and produces ATP molecules. ATP molecules transport chemical energy that is
required for metabolic processes.

Energy from glucose oxidation

The complete oxidation of glucose to CO2 and H2O is shown by the following equation.

1 Glucose molecule + 6 oxygen molecules

𝑦𝑖𝑒𝑙𝑑𝑠
→
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6 carbon dioxide molecules + 6 water molecules + energy (30-32 ATP molecules)

What is ATP?

ATP (adenosine triphosphate) transports chemical energy that is required for metabolic
processes. ATP carries 3 phosphate groups that are negatively charged and repel
each other. For this reason, energy is released when ATP is hydrolyzed to ADP
(adenosine diphosphate) by removing one phosphate group. This energy can be used
for metabolic processes that require energy (like gluconeogenesis, the formation of
glucose).

In contrast, processes that generate energy (like glycolysis, degradation of glucose)

recycle ADP to ATP by attaching a phosphate group to the ADP molecule.
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Gluconeogenesis

When dietary intake of carbohydrate is limited and the blood glucose concentration
declines, hormones trigger accelerated glucose synthesis from non-carbohydrate
sources, namely:

• lactate
• pyruvate
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• glycerol (a catabolic product of triacylglycerols, the stored form of fat)

• certain amino acids

The process of producing glucose from such compounds is termed gluconeogenesis.

Gluconeogenesis essentially reverses the glycolytic pathway. It synthesizes glucose
and consumes ATP rather than producing ATP. However, three reactions in the
glycolytic sequence are highly exergonic (energy producing), tightly regulated and
irreversible.
Therefore, gluconeogenesis is not literally the reverse process of glycolysis: the
process of gluconeogenesis requires that the irreversible reactions are either bypassed
or circumvented by other enzyme systems.

You don’t need to understand this in detail, but for example, one of the irreversible
reactions is the last step of glycolysis, the pyruvate formation. Since this reaction can’t
be reverted, pyruvate has to be converted to oxaloacetate (important TCA cycle
intermediate), which can be transferred into phosphoenolpyruvate (PEP), the glycolysis
intermediate, which is used for pyruvate formation.
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Take-home message: The reactions in gluconeogenesis (the formation of glucose

from non-carbohydrate sources) are basically the reverse process of glycolysis, except
for 3 reactions that are irreversible and need to be bypassed. The body preferentially
uses carbohydrates from your diet to obtain glucose, but it can synthesize its own
without dietary carbohydrates.

The tricarboxylic acid (TCA) cycle

The tricarboxylic acid (TCA) cycle, also called the Krebs cycle or the citric acid cycle, is
at the forefront of energy metabolism in the body. It can be thought of as the common
and final catabolic pathway because products of carbohydrate, fat and amino acids that
enter the cycle can be completely oxidized to CO2 and H2O with an accompanying
release of energy.
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More than 90% of the energy released from food is estimated to occur due to TCA
cycle oxidation. Not all the substances entering the cycle are totally oxidized, however.
Some TCA cycle intermediates are used in the formation of glucose by the process of
gluconeogenesis, and some can be converted to certain amino acids by transamination
(the transfer of an amino group from one amino acid to a α-keto acid).

In a process called decarboxylation, CO2 is removed from pyruvate, the product of

glycolysis, to form acetyl-CoA. The product of pyruvate is acetyl, which is coupled to
Coenzyme A (CoA) that functions as a carrier. Acetyl-CoA is incorporated into
oxaloacetic acid to form citric acid and subsequently lost as CO2 in the decarboxylation
step of the TCA cycle. Two important products of the TCA cycle are NADH and FADH2.
These products can be used to reduce O2 to H2O in a process that is called oxidative
phosphorylation, during which ATP is formed.

Another product of the TCA cycle is GTP, which has a similar function to ATP but
possesses higher ‘reaction specificity’: it can only be used for specific reactions.

Take-home messages: The TCA cycle is an important catabolic pathway in which:

• Carbohydrates, fatty acids and amino acids are degraded to produce energy.
• Reduction equivalents NADH and FADH2 are formed (both are used in oxidative
phosphorylation to produce energy).
• Intermediates are produced that can be used for glucose and amino acid
production.

Oxidative phosphorylation

Oxidative phosphorylation is a metabolic pathway in which NADH and FADH2 are

oxidized to form energy that is used for ATP production. Thereby, oxygen is reduced to
water. For this reason, oxidative phosphorylation is only active under aerobic
conditions.
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‘Fat burns in the flame of carbohydrates’

You may have heard this saying. Though it’s not really important in practical terms, you
may be asked about it. Here’s what it means. Fat is degraded to acetyl-CoA in order to
enter the TCA cycle. Acetyl-CoA is produced by fatty acid oxidation and amino acid
catabolism, in addition to being derived from pyruvate as a result of glycolysis. An
increase in acetyl-CoA leads to an imbalance between the amounts of acetyl-CoA and
oxaloacetate, which condense one-to-one in the TCA cycle. To keep the TCA cycle
functioning, oxaloacetate and/or other TCA cycle intermediates that can form
oxaloacetate must be replenished in the cycle. The body has a mechanism for this;
oxaloacetate, fumarate, succinyl-CoA and α-ketoglutarate (all intermediates of the TCA
cycle) can all be formed from certain amino acids, but the single most important
mechanism for ensuring an ample supply of oxaloacetate is the reaction that forms
oxaloacetate (four carbons) directly from pyruvate (three carbons, product of
glycolysis) by the addition of CO2.

In short, energy production from fat (‘fat burning’) is fuelled by (‘the flame of’)
carbohydrates. However, protein can also fuel fat burning.

Urea cycle

When amino acids are metabolized for energy, it is necessary to remove the amino
group in order to oxidize their carbon skeleton in the TCA cycle. The amino group is
removed in processes that are called deamination and transamination. The removed
amino groups are combined with CO2 (formed through oxidation of the carbon skeleton
in the TCA cycle) to form urea that is excreted.
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A summary of the metabolic pathways via which your body harvests energy from the
macronutrients in your food and discards the waste products.
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Further reading
If you are interested in the nitty gritty of biochemistry, the book Advanced Nutrition and
Human Metabolism is a great reference. It is difficult to read, however, and contains far
more information than you need to know as a nutritionist, so all the important topics
from that book are summarized in a more reader friendly format in the course
documents.
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Learning objectives & example exam questions

This module should teach you basic biochem terminology and how the body produces
energy. All of this will be detailed further and repeated in the sections where it
becomes relevant for practical application, but you should at least understand the take-
home messages and images for now.