THE MOLECULAR MEANING OF LIFE

Assist. Prof. Derya CANSIZ

Istanbul Medipol University
School of Medicine
Biochemistry Deparment

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The Hierarchy of Life

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 Biomolecules in Our Body

• Carbohydrates • Vitamines
• Lipids • Minerals
• Proteins • Hormones
• Nucleic acids

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• Molecules consisting of atoms function in many mechanisms in the
organism.
• Carbohydrates, lipids and proteins are macromolecules
• Of these macromolecules, carbohydrates consist of monosaccharides,
disaccharides, and polysaccharides.
• Glucose is also involved in carbohydrate metabolism. Besides glucose,
maltose and fructose are also monosaccharides.

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• Lipids consist of ….

• Proteins consist of…

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(construction, re-synthesis)

If there is no need for energy

(destruction)

If there is need for energy

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 Glycolysis
Citric acid
cycle Brain
Heart
β- oxidation
Citric acid
cycle

Keton bodies

Adipose tissue
Glycolysis Glycogen
Glycolysis
Glycogenesis
Triglyceride Fatty acid Triglyceride

β- oxidation β- oxidation
Gliserol
Liver

VLDL
Lactate
Alanine

Fatty acid Proteins Glycogen

β- oxidation Proteolysis Glycolysis
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Muscle
Bloodstream and Organs

• Blood is a tissue that carries

the oxygen of the air, macro-
and micronutrients taken in
the diet, and various
molecules that emerge as a
result of metabolism to the
necessary organs.
• It is called blood tissue
because blood, like other
organs, is a unique tissue.

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• Tissues benefit from different metabolic pathways to provide their energy
needs.
• For example, beta oxidation and citric acid cycle occur in the heart for
energy needs. In addition, energy is provided to the heart with ketone
bodies obtained from the liver.
• In the brain, energy is obtained through glycolysis and the citric acid
cycle. In addition, ketone bodies provide energy to the brain during long-
term fasting.
• Ketone bodies are metabolized in the liver and go to the brain and energy
is obtained in this way in case of long-term fasting.
• While energy is provided in the muscles by beta oxidation and glycolysis,
lactate synthesis from the muscles provides lactate to the heart and
alanine amino acid is provided by proteolysis.
• Beta oxidation takes place in adipose tissue, triglycerides are broken
down and glycerol and fatty acid are formed. It can then be used for
energy recovery.

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Nutrients taken with a diet

• After the nutrients taken in the diet are broken down into the smallest
molecules that can pass through the cell in the digestive system
(digestion), they are absorbed (absorption) into the blood and then
distributed to the tissues.
• It encounters anabolic (construction, re-synthesis) and catabolic
(destruction) reactions in tissues.
• At the end of catabolic reactions, new by-products and energy (ATP) are
produced.

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 Lipids
Fatty acid

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Fate of nutrients taken with diet

• The catabolism of macromolecules, such as protein, carbohydrates and

lipids we received with the diet, the latest products are observed.

• The final product of proteins is the final product of urea, carbohydrates

and lipids; CO2, H20 and energy (ATP).

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• During these reactions, approximately 300-400ml of water is produced per day.
• This water is called ‘’metabolic water’’.
• Since chemical reactions does not occurs without water. It is also called living
water.

Lipids
Fatty acid

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• After the carbohydrates, proteins and lipids are taken into the body with a
diet, they are included in the metabolism in the organism.
• As a result of glucose intake after diet, it is either stored as lipid or used
as energy, depending on the energy status of the body.
• Glucose enters the glycolysis metabolism and is broken down to
pyruvate. As a result of the breakdown to pyruvate, it enters TCA to
obtain energy as ATP and water are obtained.
• If it is to be stored (if the body does not need energy), TAG synthesis is
provided by being included in lipid synthesis (by lipogenesis).

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• Proteins, carbohydrates and lipids are broken down after they are taken into the body.
• The end product of proteins is urea.
• In normal condition, there are 20-40mg/dL urea in the blood, 20-30mg/day in the
urine.
• After protein function is completed, the end product urea excreted.

Lipids
Fatty acid

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• Carbohydrates break down in enterosit and enter the blood and tissue.
• Glucose breaks down to lactic acid in aneorabic condition,
• if there is O2 Glucose enter the citric acid cycle as Pyruvic acid, then it is converted
acetyl CoA and enter the citric acid cycle to obtain high level enegry.
• During these reactions, approximately 300-400ml of water is produced per day.

Lipids
Fatty acid

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• Lipids taken with diet enter into the citric acid cycle as Fatty acid.
• If the organism does not need energy, they are stored by going from
acetyl CoA to lipogenesis and forming lipids again.

Lipids
Fatty acid

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 Diabetic ketoacidosis

• Glucose is the first energy source for the cell. The second is lipid the last source is
the protein.
• If there is no insulin, glucose does not enter the citric acid cycle, to obtain energy
fatty acid used instead of glucose and Diabetes occurs in the non-controlled
diatebes due to high level keton bodies decrease blood pH diabetic keto-acidosis
occurs (DKA).
• Blood pH should be 7.2–7.4 In contrast, acidosis or alkalosis occurs.
• Fasting Blood Glucose Level: 70-100 mg/dL

Metabolic acidosis is characterized by an increase in the hydrogen ion concentration in the

systemic circulation that results in an abnormally low serum bicarbonate level.

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19
 Article

• During the early stages of feeding with KD, the

blood glucose concentration decreases, and the
insulin/glucagon ratio decreases. Since
carbohydrate intake is low, high glucagon
concentration causes glycogen breakdown in the
liver.
• As a result of suppression of gluconeogenesis,
glucose begins to be insufficient for the body.
The primary energy source for the brain is
glucose.
• Therefore, ketone bodies (Acetone, Acetoacetate
and beta hydroxybutyrate) are synthesized in the
liver mitochondria (ketogenesis) and given to the
blood as an alternative energy source in cases
where glucose is too low (Paoli et al., 2014)

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• The citric acid cycle is our life cycle.
• In insulin deficiency, if glucose cannot enter the cell, fatty acids begin to
be used for energy.
• Therefore, people with diabetes become weak.
• Losing weight is good but losing weight in this way leads to disruption of
metabolism, the emergence of ketone bodies, these acidic molecules
lowering the blood pH, and the organism to go to acidosis, that is, the
patient goes to the intensive care unit.

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• Intestinal cells are one of the most active cells. Nutritional elements taken
with the diet and the smallest molecule have its unique transport system.
• Glucose is connected to a carrier by combining to enter the enterocite.
• The glucose leaving the sodium in the intestinal cell is connecting to their
transporter (GLUT) by connecting to the blood.

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 The Oral Glucose Tolerance (OGTT) Test
The fate of the glucose into the blood

• In the oral glucose load (OGTT) test, which is taken with diet or for
diagnostic and therapeutic purposes, blood glucose reaches its maximum
level at the end of one hour and drops to the reference value of the
individual at the end of the second hour.
• With glucose intake, the amount of insulin also moves parallel to glucose.
• However, fatty acids in the blood follow a reverse path.

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 Metabolic Pathways of the Glucose

• Conversion of glucose to glycogen for storage in the liver (glycogenesis)

• Conversion of liver glycogen to blood glucose (Glycogenolysis)

• Synthesis of blood glucose by the liver (Glyconeogenesis)

• Utilization of glucose by anearobic oxidation (Glycolysis)

• Utilization of glucose by aerobic oxidation (Citric acid cycle)

• Utilization of glucose by Pentose phosphate pathway

• Synthesis of glucuronic acid by Uronic acid pathway

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 Metabolic Control of Glucose

• Metabolic control of glucose is important. In order to prevent

hyperglycemia and hypoglycemia, blood glucose is regulated in various
metabolic pathways.

• Glucose is given to the blood from three different sources.

1. Conversion of dietary carbohydrates to glucose
2. Glucose released from glycogen stores into the blood by glycogenolysis
3. Glucose synthesized from some amino acids, lactic acid and glycerol by
gluconeogenesis.

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Glucagon and Insulin hormone on liver metabolism

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Increase/ Decrease Blood Glucose

• When blood glucose rises, glucose is stored as glycogen in tissues,

mainly in the liver, and blood glucose decreases because of insulin
hormone.
• On the contrary, when blood glucose decreases, the glucose in the
liver stores is released into the blood by means of glucagon and
adrenaline, and blood glucose increases.

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 Physiological Significance of Formation of
Glucuronides
DETOXIFICATION
• Any substance that combines with glucuronic acid is better soluble in water and
easily leaves the organism.
• As a result of this detoxification, bile or urine; steroids, bilirubin, morphine,
salicylic acid etc. can be excreted.
• The inability to conjugate bilirubin, which is common in liver diseases, leads to
the precipitation of bilirubin exceeding its processing capacity (jaundice) in the
tissues.
For Treatment
• If the bilirubin level is high, the baby is
subjected to light therapy under lamps
emitting light in a special wavelength
called "phototherapy".
• This light allows the bilirubin that causes
jaundice to dissolve in the urine and be
excreted from the body.

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 Cori Cycle or Lactate Cycle

Liver clears muscle waste, but with what? → gluconeogenesis

It lowers the lactate rate….
This cycle provides to convert lactate to glycogen.

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Liver-Muscle and Glucose

• Lactic acid is produced anaerobic condition (without oxygen)

• The acidic substance is removed in liver by gluconeogenesis, so it is
removed from blood and is included to glucose synthesis.
• Thus, lactic acid, which is waste and harmful, has returned to glucose
which is very useful molecule.

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 Intensive care and lactate level-O2 saturation

• Lactate is measured in intensive care patients. to

monitor glycolysis.
• The increase in the amount of lactate causes the patient
to go to acidosis and it is decided that this patient is in
intensive care.

Pulse Oximetry
• The blood lactate level is normally between 0.5-1.8
mmol/L in the form of production and reuptake.
• If the O2 saturation is
• The level considered abnormal is 2 mmol/L and above. below 95, it means that the
• If the lactate is over 4 mmol/L, it is a value determined citric acid cycle cannot use
for high-risk patients. glucose.
• It continues with
glycolysis, that is, lactate
increases and blood pH
decreases.

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Thank you for your attention

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