Edited by

Dr.Liniyanti D Oswari, MNS,MSc.

What is biochemistry?
Living things are composed of lifeless
molecules. When these molecules are
isolated and examined individually, they
conform to all the physical and chemical
laws that describe the behavior of inanimate
matter.

-Albert Lehninger
(1917-1986)
Science concerned with
chemical basis of life in Human
being.
Science concerned with the
chemical constituents of living
cells and with the reaction and
process that they undergo

3
Course Overview
Carbohydrate Metabolism
Sugars, Starches, Digestion, Absorption, Energy
Lipid Metabolism
Digestion, Absorption, Transport, Mobilization
Amino Acids and Proteins
Production, Breakdown, Conversion
Nucleic Acids, DNA and RNA
Production, Breakdown
Medical Genetics
Metabolism:

the sum total of chemical (and physical)
changes that occur in living organisms,
and which are fundamental to life.
Concise Encyclopedia of Biochemistry
Anabolism
Catabolism
Conversion into derivatives
e.g histidine to histamine
Tyrosine to thyroxines
Tyrosine to melanin
Choline to acetylcholine
Catabolism: exergonic oxidation
(Pemecahan dari molekul besar ke
molekul lebih kecil contoh
Sukrosa dg enzim Sukrase jadi
Glukosa & Fruktosa)
Anabolism: endergonic biosynthesis
(Mensintesa dari molekul kecil kemolekul
lebih besar contoh Asam amino memben
tuk Protein Otot)
Metabolism
Products from one provide substrates for the other.
Anabolism and catabolism share many intermediates.
The three stages of catabolism.
Stage 1: Proteins,
polysaccharides, and lipids are
broken down into their
component building blocks.
Stage 2: The building blocks
are degraded into the common
product, the acetyl groups of
acetyl-CoA.
Stage 3: Catabolism converges
to three principal end products:
water, carbon dioxide, and
ammonia.
FOOD
Proteins Carbohydrates
Fats
Amino acids
Fatty acids
and glycerol
Glucose
Glycolysis
Pyruvate
Acetyl CoA
Krebs (Citric
acid) cycle
Oxidative
phosphorylation
Gut-Brain Peptides
(only a few out of many)
Chemical signals from the G.I. Tract to the Brain

Short-term Regulators
Last for minutes to hours
Make us want to start eating and stop eating

Long-term Regulators
Work over periods of weeks to years
Regulate our caloric intake & energy spent and amount of
adipose tissue
Short-Term Regulators
Ghrelin
Secreted from parietal cells when stomach empty & stops within
an hour of eating
Produces sensation of hunger & starts up eating
Causes hypothalamus to release GHRH ( hGH)

Peptide YY
Secreted by ileum & colon in response to food in the stomach, in
proportion to calories consumed
Signals satiety & stops eating

Cholecystokinin
Secreted by duodenum & jejunum
Produces appetite-suppressing effect via Vagus N.
Long-Term Regulators

Leptin
Secreted by adipocytes in proportion to amount of stored fat
Primary way brain knows how much body fat is stored
Obesity is related to receptor unresponsiveness

Insulin
Secreted by beta cells in pancreas
Stimulates glucose & amino acid uptake
Promotes glycogen & fat synthesis
Additional way brain knows how much body fat is stored (effect
weaker than leptin)
15
Digestion is the first step of catabolism
Carbohydrates glucose, fructose,
galactose

Proteins amino acids

Lipids glycerol
fatty acids


16
Substances that connect metabolic pathways
In reduction, coenzymes accept H atoms
In oxidation, coenzymes remove H atoms
FAD (flavin adenine dinucleotide)
FAD + -CH
2
-CH
2
- FADH
2
+ -CH=CH-

NAD
+
(nicotinamide adenine dinucleotide)
NAD
+
+ -CH-OH NADH + H
+
+ -C=O




Metabolism.

All chemical & physical changes that
occur in living organisms appear to obey
the universal laws of thermodynamics.

Reactions must be thermodynamically
possible, even if seemingly unfavorable,
for them to occur in biochemistry.
Certain metabolic pathways are
compartmentalized in different cell
sites.
Glycolysis occurs in the cytosol.
The Krebs cycle reactions occur in the
mitochondrial matrix.
Other oxidative reactions occur in the
microsomes.
In photosynthesis, some pathways are in
the chloroplast.
Compartmentation of Metabolism
19
* Biochemistry studies have
illuminated many aspects of
health & disease
* the study of various aspects of
health & disease has opened up
new areas of biochemistry
20
Biochemistry
Nucleic acid Protein lipid
Carbohydrates
Geneticdisease Sickle cell anemia
Medicine
arteriosclerosis Diabetes mellitus
From Stryer
Let us take
the case of
the
glycolytic
pathway,
which has
several
enzyme-
catalysed
steps:
As can be seen, some reactions of glycolysis require
an input of energy, whereas others release it.
Thus by coupling unfavorable reactions to
reactions that can go spontaneously, desired
biomolecules can be synthesised without flouting
the laws of thermodynamics.
Since many of the effective units of
metabolism are the metabolic pathways, how
are they controlled?

Let us go back to look at a simple reaction
catalysed by a Michaelis-Menten enzyme.
V
max
.[S]
K
M
+ [S]
Vo =
Vmax is the maximum velocity which
the amount of enzyme used here can
achieve.
[S] is the concentration of substrate
being varied here.
K
M
is defined as the ratio of the rate constants of the
component reactions in the derivation of the rate equation:

Enzyme + Substrate ES complex Enzyme + Product

k
-1
k
2
E + S ES E + P
k
1
k
-1
+ k
2
K
M
=
k
1


Aerobic respiration
Aerobic metabolic pathways (using oxygen) are
used by most eukaryotic cells

Fermentation
Anaerobic metabolic pathways (occur in the
absence of oxygen) are used by prokaryotes and
protists in anaerobic habitats

Aerobic respiration and fermentation both
begin with glycolysis, which converts one
molecule of glucose into two molecules of
pyruvate

After glycolysis, the two pathways diverge
Fermentation is completed in the cytoplasm,
yielding 2 ATP per glucose molecule
Aerobic respiration is completed in mitochondria,
yielding 36 ATP per glucose molecule if all
processes there go to completion
Three stages
Glycolysis (carried out in cytoplasm; necessary to
set stage for mitochondrial processes that follow
Acetyl-CoA formation during Krebs cycle
Electron transfer phosphorylation (ATP formation)
C
6
H
12
O
6
(glucose) + O
2
(oxygen)
CO
2
(carbon dioxide) + H
2
O (water)

Coenzymes NADH and FADH
2
carry electrons and
hydrogen

Typically, the breakdown of one glucose
molecule yields 36 ATP for all three stages:

Glycolysis: 2 ATP

Acetyl CoA formation and Krebs cycle: 2 ATP

Electron transfer phosphorylation: 32 ATP



Fermentation pathways break down
carbohydrates without using oxygen

The final steps in these pathways regenerate
NAD
+
but do not produce ATP

Glycolysis is the first stage of fermentation
Forms 2 pyruvate, 2 NADH, and 2 ATP

Pyruvate is converted to other molecules, but
is not fully broken down to CO
2
and water
Regenerates NAD
+
but doesnt produce ATP

Provides enough energy for some single-
celled anaerobic species

Alcoholic fermentation
Pyruvate is split into acetaldehyde and CO
2
Acetaldehyde receives electrons and hydrogen from
NADH, forming NAD
+
and ethanol

Lactate fermentation
Pyruvate receives electrons and hydrogen from
NADH, forming NAD
+
and lactate

Fig. 8-10b, p. 133
Fermentation gives rise to doughs by CO
2
release.

Slow-twitch muscle fibers (red muscles)
make ATP by aerobic respiration
Have many mitochondria
Dominate in prolonged activity

Fast-twitch muscle fibers (white muscles)
make ATP by lactate fermentation
Have few mitochondria and no myoglobin
Sustain short bursts of activity


Fermentation pathways start with glycolysis

Substances other than oxygen accept
electrons at the end of the pathways

Compared with aerobic respiration, the net
yield of ATP from fermentation is very small

Pathways that break down molecules other
than carbohydrates also keep organisms alive

In humans and other mammals, the entrance
of glucose and other organic compounds into
an energy-releasing pathway depends on the
kinds and proportions of carbohydrates, fats
and proteins in the diet
Its a constant balancing act

When blood glucose concentration rises, the
pancreas increases insulin secretion
Cells take up glucose faster, more ATP is formed,
glycogen and fatty-acid production increases

When blood glucose concentration falls, the
pancreas increases glucagon secretion
Stored glycogen is converted to glucose

About 78% of an adults energy reserves is
stored in fat (mostly triglycerides)

Enzymes cleave fats into glycerol and fatty
acids
Glycerol products enter glycolysis
Fatty acid products enter the Krebs cycle

Compared to carbohydrates, fatty acid
breakdown yields more ATP per carbon atom


Enzymes split dietary proteins into amino
acid subunits, which enter the bloodstream
Used to build proteins or other molecules

Excess amino acids are broken down into
ammonia (NH
3
) and various products that can
enter the Krebs cycle
Amino acids are absorbed
from the small intestine

About 50% from diet
About 25% from dead epithelial cells
About 25% from digested enzymes
1) Amino acids used for protein synthesis

Amino acids can be actively transported
into body cells & used to build proteins
What are some
examples of proteins?
20 different amino acids are used to synthesize
proteins

8 called essential amino acids because they
must come from the diet

Histidine & arginine are semi essensial amino
acids for adult and essential amino acids for
baby.

Foods that contain all the essential amino acids
are called complete proteins, for example;
eggs, milk, meat.

The nonessential amino acids can be produced by
the body through a process called
transamination

Transamination = transfer of an amino group
(NH
2
) from an abundant amino acid to a keto
acid to make a new amino acid

Keto acid + amino group (NH
2
) amino acid
2) Amino acids can be used as fuel, or a source of
energy

First step is deamination, which is removal of an
amino group (NH
2
) from an amino acid creating
a keto acid

Amino acid Keto acid + amino group
(NH
2
)

p 1023
Depending on which
amino acid is
deaminated,

the keto acid may be
converted to;
Pyruvic acid
Acetyl CoA
One of the acids of
citric acid cycle

p 1023
Pyruvic acid could be
converted back into
glucose by cells in the
kidney or liver

This is an example of
gluconeogenesis, which
is making glucose from a
non-carbohydrate
source
p 1023
The amino group is
transferred to ketoglutaric
acid, making glutamic acid,
that travels to the liver & is
converted back to
ketoglutaric acid


Left over ammonia (NH
3
) is
converted to urea
p 1025
Absorptive State = 4 hours during & after a meal
Nutrients are being absorbed & then immediately used or stored

Postabsorptive State = stomach & intestine are empty
Stored fuel molecules are used for energy
54
Biochemical research has
impact on nutrition and
preventive medicine

all disease has a
biochemical basis


55
(1)Physical agent:

mechanical trauma,extremes of temperature,
sudden changes in atmospheric pressure,
radiation, electric shock

(2)Chemical agents:
drugs, certain toxic compounds,
therapeutic drugs

56
(3)Biologic agents:
Viruses, Bacteria,Fungi,
Higher forms of parasites
(4)Oxygen lack :
loss of blood supply, depletion of the
oxygen-carrying capacity of the blood,
poisoning of the oxidative enzyme
(5) Genetic disorders:
Congenital , molecular






57
(6) Immunology reaction:Anaphylaxis,
Autoimmune disease

(7) Nutritional imbalances:Deficiencies,excesses

(8) Endocrine imbalances :hormonal deficiencies,
hormonal excesses





58
Biochemical studies contribute to
diagnosis, prognosis & treatment

Disease Causes
Scurvy deficiencies of vitamin C
Rickets deficiencies of vitamin D

Arteriosclerosis genetic,dietary environment factors

Phenylketonuria mainly mutation the gene coding
phenylalanine hydroxylase






59
Disease causes
Cystic fibrosis mutation in the gene coding the
CFTR Protein

Cholera exotoxin of Vibrio Cholera

Diabetes type I genetic and environment factors
resulting in deficiency of insulin
60
Many biochemical studies illuminate
disease mechanisms & disease inspire
biochemical research

Use example
1.To act as screening use of measurement of blood
tests for the early tyrosine or TSH in the
diagnosis of certain diseases neonatal diagnosis of
congenital hypothyroidism

61
Use example
2.to reveal the fundamental demonstration of the genetic
causes &mechanisms defects in Cystic Fibrosis.
of diseases
3. to suggest rational use of a diet low in Phenyl-
treatment of diseases alanine for the treatment of
phenylketonuria
4. to assist in the diagnosis use of the plasma enzyme
of specific disease CK-MB in the diagnosis 0f
Myocardial Infarction.
62
Use example
5. the progress of certain ALT in monitoring the
disease progress of infectious
hepatitis
6. To assist in assessing the use of measurement of
response of diseases to therapy blood CEA in certain
patients who have
been treated for cancer
of the colon