BIOCHEMISTRY II 3RD STAGE

LECTURE 8
CONVERSION OF AMINO ACIDS
TO SPECIALIZED PRODUCTS

Dr. omar Dawood salman

Creatine
 Creatine is an organic compound with the nominal
formula (H2N)(HN)CN(CH3)CH2CO2H. This species
exists in various modifications (tautomers) in solution.
Creatine is found in vertebrates where it facilitates
recycling of adenosine triphosphate (ATP), the
energy currency of the cell, primarily in muscle and
brain tissue. Recycling is achieved by converting
adenosine diphosphate (ADP) back to ATP via
donation of phosphate groups. Creatine also acts as
a buffer.
 Creatine Synthesis

•Amidinotransferase is a mitochondrial enzyme catalyzing

the rate-limiting step of the pathway
•Methyltransferase uses S-Adenosylmethionine as a one-
carbon donor to yield creatine
•Nearly half of muscle creatine results from dietary intake
•Creatine spontaneous cyclizes to creatinine, which is
secreted in the urine
•Serum creatinine is routinely measured on admission as a
test of kidney function. Kidney impairment results in elevated
serum creatinine
 Catecholamines
•Biologically-active water-soluble amines derived from
tyrosine that serve as neurotransmitters in the CNS and
as hormones in circulation in response to psychological
stress (“fight or flight response”) or hypoglycemia:
Epinephrine (adrenaline)
Norepinephrine (noradrenlaine)
Dopamine

Tyrosine is the precursor for the synthesis of

catecholamines.
The conversion of tyrosine to catecholamines occurs in
the adrenal medulla and the central nervous system
•Tyrosine hydroxylase is the rate-limiting step.
•DOPA decarboxylase is a pyridoxal-5’-phosphate-dependent
enzyme
•Dopamine -hydroxylase is a Cu2+-containing enzyme
•Catecholamines act at - and -adrenergic receptors

•Pleiotropic neurotransmitter (Producing or having multiple

effects from a single gene) of serotonergic neurons of the CNS
and enterochromaffin cells of the GI.
•Synthesized predominately in the GI tract
•Tryptophan hydroxylase (TPH) is rate-limiting step
Melatonin is a natural product found in plants and animals. It is
primarily known in animals as a hormone released by the pineal
gland in the brain at night, and has long been associated with
control of the sleep–wake cycle.

Melatonin biosynthesis
Histamine Synthesis

•Histamine is an extracellular chemical messenger

mediating a range of cellular responses including
allergic and inflammatory reactions

•Synthesized by histidine decarboxylase, a

pyridoxal-5’-phosphate-dependent enzyme
•Four classes of histamine receptors.

•H1 blockers blocks allergic reactions, hives and

itching, and causes drowsiness
•H2 blockers blocks acid secretion from parietal
cells of stomach
Glutathione Synthesis
Gamma aminobutyric acid (GABA) is a naturally occurring
amino acid derivative that works as a neurotransmitter in
your brain. Neurotransmitters function as chemical
messengers. GABA is considered an inhibitory
neurotransmitter because it blocks, or inhibits, certain brain
signals and decreases activity in your nervous system.
Nitric oxide: is a molecule that's produced naturally by
your body, and it's important for many aspects of your
health. Its most important function is vasodilation, meaning
it relaxes the inner muscles of the blood vessels, causing
them to widen and increase circulation.
Hippuric Acid is an acyl glycine produced by the
conjugation of benzoic acid and glycine, found as a normal
component in urine as a metabolite of aromatic compounds
from food.
Hippuric acid can be used to study cell biology, chemical
biology, bioactive small molecules, amino acid derivatives,
peptide synthesis, chemical synthesis and nutrition.
Taurine is a type of chemical called an amino sulfonic acid. It
occurs naturally in the human body and has many important
functions. Taurine is found in large amounts in the brain,
retina, heart, and blood cells called platelets. The best food
sources are meat, fish, and eggs. The body usually
makes taurine on its own.
 Heme Synthesis
HEME-CONTAINING PROTEINS

• Hemoglobin

• Myoglobin

• Cytochromes

• Catalase

• Some peroxidases
Heme structure:
➢ a porphyrin ring coordinated with an atom of iron
➢ side chains: methyl, vinyl, propionyl

Heme is complexed with proteins to form:

Hemoglobin, myoglobin and cytochromes
Mitochondria Cytosol Mitochondria
Synthesis of δ-aminolevulinic acid:

induced by: drugs (barbiturates), Pyridoxal phosphate

oral contraceptive pills (vit. B6)
Formation of porphobilinogen:

inhibited by lead
Iron metabolism:
➢ Recommended dietary allowance 10-15 mg (only 10-15% is normally
absorbed)

Iron distribution:

g %

Hemoglobin 2,5 68

Myoglobin 0,15 4

Transferrin 0,003 0,1

Ferritin, tissue 1,0 27

Ferritin, serum 0,0001 0,004

Enzymes 0,02 0,6

Total 3,7 100

Intestinal absorption of iron:
- in the duodenum
- regulation (by the synthesis of apoferritin
within mucosal cells)

1. The heme iron (unknown mechanism)

2. The nonheme iron
• is not readily absorbed (chelates with
oxalates, phytates, etc.)
• vit. C increases the uptake
Iron transport:
➢ Transferrin (Fe3+)
➢ Transferrin + Fe3+ + CO32- → Transferrin • 2(Fe3+CO32-)

- only one third saturated with iron

- unsaturated transferrin protects againsts infections (iron overload
and infection)
➢ Lactoferrin
- binds iron in milk
- antimicrobial effect (protects newborns from gastrointestinal
infections)
➢ Haptoglobin - binds hemoglobin in the plasma
Iron storage: Ferritin (Fe3+)
- storage of iron (hepatocytes, RES, muscles)
- in the blood → sensitive indicator of the amount of iron in the body

➢Hemosiderin The breakdown of heme gives rise to biliverdin and iron.

The body then traps the released iron and stores it as hemosiderin in tissues.
Iron-containing proteins:
1. Heme proteins
Hemoglobin
Myoglobin
Enzymes that contain heme as their prosthetic group
(catalase, peroxidase, NO synthase)

2. Nonheme proteins
Transferrin
Ferritin
Enzymes that contain iron at the active site
Iron-sulphur proteins
Iron deficiency: Symptoms
reduction of iron stores in liver and bone marrow
decrease in the amount of plasma ferritin
decrease in the percentage saturation of serum transferrin
decrease in the level of Hb, morphological changes of
erythrocytes
microcytic hypochromic anemia (e.g excessive menstrual flow,
multiple births, GIT bleeding)
Iron overload (hemochromatosis):
Causes
➢ genetic - iron uptake regulation
➢ treatment of patients with hemolytic anemias
➢ excessive ethanol and iron ingestion
Symptoms
accumulation of iron in the liver, pancreas and heart
Degradation of heme:
Conversion of heme to bilirubin:

ER enzyme
system

the major source is Hb

Formation of bilirubin diglucuronide:

increase the water

solubility of bilirubin
Hyperbilirubinemia
➢ Elevated bilirubin levels in the blood (>10 mg/l); bilirubin may diffuse
into peripheral tissues, giving them a yellow color (jaundice)
➢ Cause:
1. Pre-hepatic: excessive formation of bilirubin by increased
degradation of erythrocytes (icterus neonatus, hemolytic anemia)
2. Hepatic: insufficient processing of bilirubin as a result of
liver defects (hepatitis, liver toxic damage, cirrhosis, hepatic
failure)
3. Post-hepatic: by impaired excretion of gall bladder (obstructive
jaundice due to gallstones, inflammation of biliary tract)

➢ Unconjugated bilirubin can cross the blood-brain barrier, leading to

brain damage
➢ Jaundice in neonates (increased bilirubin degradation+immaturity of
the conjugation enzymes): phototherapy – isomerization of bilirubin to
more soluble pigments
Type Cause Example Frequence

Prehepatic Hemolysis Autoimmune Rare

Haemoglobinopathy According to the
region

Hepatic Infection Hepatitis A,B,C Very common

Damage Alcohol, drugs Common
Genetics Gilbert´s syndrome 1 in 20
Wilson´s disease 1 in 200 000
α1-Antitrypsin deficiency 1 in 1000
Autoimmune Chronic hepatitis Rare
Newborn Physiologic Very common
Posthepatic a) Intrahepatic 1. Drugs Common
bile ducts 2. Primary biliary cirrhosis Rare
3. Cholangitis Common
b) Extrahepatic 1. Gallstones Very common
bile ducts 2. Pancreatic cancer Rare
 Bilirubin Urobilinogen
blood urine deriv. in feces blood urine
Prehepatic ↑↑(UC) N ↑ ↑ ↑

Intrahepatic ↑↑(both) ↑ N ↑↑ ↑↑

Posthepatic ↑↑(C) ↑ ↓ ↓ ↓