Transcript Protein mteabolism L..

Methionine amino acid:
Essential amino acid
It is used as methyl donor The active form of
methionine as methyl donor is S-adenosyl methionine
(SAM)
+
S-adenosyl methionine (SAM)
Functions of methionine:
1- SAM act as methyl donor in :
A- synthesis of creatine (see synthesis of creatin from glycine).
B- conversion of norepinephrine into epinephrine
Synthesis of creatin
2-Methionine participates with serine in the synthesis of cysteine
amino acid as follow
↓
homoserine
↓
Homocystinuria or hyperhomocysteinemia:
Is a genetic disease caused by genetic deficiency of cystathionine
synthase leading to accumulation of homomcysteine in blood
(hyperhomocysteinemia) and its excretion in urine (homocystinuria).
Symptoms: Homocysteine is toxic to CNS, cardiovascular system,
kidney, connective tissues, etc. leading to:
1- Mental retardation
2- at chilhood: osteoporosis, bone weakness and fracture (disturb
collagen biosynthesis)
3Cardiovascular diseases:
myocardial infarction
and
atherosclerosis, thrombosis
Treatment: restriction of methionine in diet
Cysteine amino acid
Non essential, formed from methionine (as before)
Glucogenic as it gives pyruvate
Functions:
1- Formation of hormones:
insulin, oxytocin and vasopressin (ADH)
2- Formation of bile salts:
Cysteine enter in the formation of taurine which combine with
cholic acid giving taurocholate (see bile salts).
3- Formation of GSH: with glycine and glutamic acid
4- Formation of cystine (by forming disulfide bond which
stabelize the protein)
Histidine amino acid
Glucogenic: it gives α-ketoglutarate
Functions:
synthesis of histamine which is local hormone, vasodilatotor
substance released in allergic diseases.
Histidine
Histamine
Serine amino acid
Glucogenic amino acid: gives pyruvate
Non essential amino acid: Synthesized from either glycine or 3phosphoglycerate
Synthesis of serine from 3-phosphoglycerate
Serine is generated in a two-step reaction from 3-phosphoglycerate.
The first step is an oxidation, the second a transamination.
Synthesis of serine from glycine:
Glycine is converted into serine by the enzyme serine
hydroxymethyl transferase.
↔
Functions of serine:
1-Synthesis of sphingomyelin
Serine + palmitoyl CoA → sphingosine base → sphingomyelin
2- Synthesis of cysteine (with methionine, see before)
3- Synthesis of glycine amino acid
Acidic amino acids:
Aspartic acid and glutamic acid
Glutamic acid
Non essential: as it is synthesized either by:
1-Transamination
2- glutamate dehydrogenase enzyme (GDH) (see before)
Glucogenic:
as it gives α-ketoglutarate by transamination or by oxidative
deamination by GDH (reversible reactions)
Functions of glutamic acid:
1- Formation of Folic acid together with p-amino benzoic acid and pteridine ring
•
•
Folic acid is a member of vitamin B complex. It plays an important role in
synthesis of purines and thymidine monophosphate (TMP) and so DNA
synthesis. Deficiency of folic acid leads to diminished DNA synthesis and
inhibit cell division resulting in meglaoblastic anemia (accumulation of large,
immature RBCs -called megaloblasts- in blood and B.M.).
Folic acid is needed for rapid cell division and growth as in infancy and
pregnancy. Many foods contain folic acid, including vegetables such as spinach,
broccoli, green beans, and potatoes. Some food as bread and cereals (corn
flakes) are fortified with folic acid.
Structure of folic acid illustrate participation of glutamic acid
1- Role of THF in purine biosynthesis:
THF is the carrier of formate
group that constitute the
carbons 2 and 8 of purine
ring
2- Folic acid is important for biosynthesis of thymidine
monophosphate (TMP) of DNA.
-3- Maturation of RBCs needs folic acid
3- detoxification of ammonia: by formation of glutamine in brain,
muscles and liver by glutamine synthetase enzyme
Glutamic acid + ammonia → glutmine
4- N3 of pyrimidines and N3, N9 of purines are deived from glutamine
3
3
9
2- Formation of GABA in brain: by decarboxylation
GABA ( γ-amino butyric acid) is an important compound in brain. Drugs that act as
agonist of GABA receptors (known as GABA analogues or GABAergic drugs) or
increase the available amount of GABA typically have relaxing, anti-anxiety and anticonvulsive effects.
Its deficiency leads to convulsion especially in children. The reaction is PLPdependent. PLP is derived from vitamin B6, so deficiency of vitamin B6 → deficiency
of GABA in brain → convulsion.
Aspartic acid
NH2
|
COOH-CH2-CH-COOH
Non essential: formed through transamination
Glucogenic as it gives oxaloacetate by transamination
Functions of aspartate:
1- Enter in urea formation: see urea cycle
-
2- N1 of purines and N1 and C4,5,6 of pyrimidines are derived from
aspartate
1
Role of aspartic acid in urea formation