Amino acid biosynthesis

• There are 2 classes of amino acids; Essential and non-

essential.
• All tissues can synthesize the non-essential amino acids.
• The nitrogen that makes up amino acids, purines, pyrimidines
and other biological molecules comes from atmospheric
nitrogen.

• Nitrogen is fixed by the action of nitrogen fixing bacteria and

blue green algae (cyanobacteria).

• Rhizobium bacteria invade the roots of leguminous plants and

form root nodules where nitrogen fixation takes place.
 Amino acid biosynthesis
• During fixation nitrogen (N2) is converted to ammonia (NH3) by
a nitrogenase complex.
• When animals feed on plants, the ammonia is assimilated into
amino acids by way of glutamate and glutamine.
• These amino acids act as carriers of the amino group for the
synthesis of other amino acids.

• Glutamate is synthesized from NH4+ and α-ketoglutarate by

the action of glutamate dehydrogenase

• Glutamine is synthesized from NH4+ and glutamate by

glutamine synthetase
Amino acid biosynthesis
 Amino acid synthesis

-Pyruvate + glutamate- alanine (alanine aminotransferase)

-Oxalo acetate + glutamate – aspartate (aspartate amino
transferase
- Asparagine- Amidation of aspartate (asparagine synthetase)
- Ribose-5-phosphate- histidine
- 3-Phosphoglycerate- Serine
 Amino acid synthesis
• Phosphoenol pyruvate ; erythrose-4-phosphate-
phenylalanine, tyrosine and tryptophan
• Tyrosine-Hydroxylation of phenylalanine
• Aspartate- methionine, lysine, threonine, isoleucine
• Serine- cysteine and glycine
Regulation of amino acid synthesis
• Occurs in the fed state

• Activated by insulin
 Amino acid derivatives
• Antioxidants-glutathione
• Neurotransmitters and signalling molecules e.g serotonin,
histamine, nitric oxide
• The pigment melanin
• Hormones- peptide hormones
• Porphyrin rings in heme

• And many more

 Amino acid degradation
• Excess amino acid is neither stored nor excreted
BUT degraded to be used as metabolic fuel
The urea cycle
 Defects
• Hyperammonemia- carbamoylphosphate synthetase (lethal;
presents with lethargy, periodic vomiting, coma and
irreversible brain damage)
• Phenylketonuria- phenylalanine hydroxylase
• Albinism- Tyrosinase
• Marple syrup urine disease- error in metabolism of
branched-chain amino acids (evident in the first week of extra
uterine life
• Histidemia- Histidase (enzyme converts histidine to
ammonia)- causes speech defects
 AKA-heme

Porphyrin synthesis
synthesis.

lead can inhibit this reaction

prosthetic group;
myoglobin/hemoglobin,catalase,
peroxidase cytochrome p450

requires Zn ,Lead acts as inhibitor

+
4 NH3

porphobilogen
 Porphyrias
 PORPHYRINS ARE SYNTHESIZED IN BOTH LIVER AND ERYTHROBLASTS
• Inherited or acquired disorders caused by a deficiency of an
enzyme in the heme biosynthetic pathway
• Commonly is congenital erythropoietic porphyria due to a
deficiency in uroporphyrinogen III synthase (cosynthase).
• Erythrocytes are prematurely destroyed; there is excretion of large
amounts of uroporphyrinogen turning urine red.
• Teeth also show strong red fluorescence when exposed to ultra
violet light due to deposition of porphrins.
• The skin is also very light sensitive because porphyrins are quite
reactive when exposed to light.
 Acute Intermittent porphyria- most prevalent porphyria affecting the liver. characterized
by over production of porphobilinogen and delta amino levulinic acid. leading to severe
abnorminal pain and neurological dysfunction
 Heme degradation
• Occurs in the reticulo endothelial cells of the liver, spleen and
bone marrow.

unconjugated
 Heme degradation
• Bilirubin is transported to the liver bound to plasma albumin.

• In the liver parenchymal cells, bilirubin undergoes conjugation with

glucuronate to convert it into a polar form done by the enzyme
glucuronyl transferase

• Conjugated bilirubin is secreted into bile and transported into the

intestines (illeum and large intestines) where it is further reduced
into urobilinogens.

• A small amount of urobilinogen is re absorbed and re-excreted thru

the liver(enterohepatic circulation)
 Hyperbilirubinemia
• The urolibilinogen in the intestines can be reduced to
stercobilinogen.

• Normally, most of the colorless urobilinogens/stercobilinogens are

oxidized to colored urobilins and stercobilins that are excreted in
urine and feaces, respectively

• Under abnormal circumstances, urobilinogen may also be excreted

in the urine

• Hyperbilirubinemia occurs when bilirubin conc exceed 2-2.5mg/dL.

Bilirubin diffuses into the tissues causing the yellow discoloration
(Jaundice); causes are many
 Detection of bile pigments
Serum bilirubin Urine Urine Fecal
urobilinogen Bilirubin urobilinogen
Normal Direct /conjugated 0-4mg/24h Absent 40-280mg/hr
(0.1-0.4 mg/dL)
Indirect/free (0.2- Absent
0.7 mg/dL)
Hemolytic Indirect ↑ ↑ Absent ↑
jaundice
Hepatic Both direct and ↓ if micro Present with ↓
indirect ↑ obstruction is micro
present obstruction
Obstructive Direct ↑ absent Present Trace or
absent
(blocked bile duct or
pancreatic duct)