Transcript Protein mteabolism

Conversion of amino acids into specialized products
Glycine amino acid
I- Non essential amino acid: as it is synthesized in the body from
serine
Serine
↔
glycine +CHO
The reaction is reversible so each of them can be converted to each
other
II- glucogenic : Being converted into serine which is converted into
pyruvate
Functions of glycine:
1- Synthesis of heme:
Glycine + Succinyl CoA → → → → → →Heme
2- Bile salt formation:
Cholic acid (bile acid) +glycine → glycocholate (bile salt)
3-Purines: C4, C5 and N7 of purines are derived from glycine
7
5
4
4- Serine: Glycine is converted into serine by the enzyme serine
hydroxymethyl transferase. Serine is then converted into pyruvate
so both glycine and serine are glucogenic
↔
5- Creatine:
- Creatine is formed of glycine + arginine + methionine amino acid
Creatine is present in blood in the free form, while in muscles it is
gained phosphate group from ATP by creatine kinase (CK) to give
creatine phosphate (creatine ~ p) or called phospho creatine (PCr.)
and ATP is converted into ADP.
creatine ~ p is the main storage form of energy in muscles and used
during muscle contraction. During intense physical exertion, ATP is
rapidly recreated from ADP by the donation of a phosphate group
from Phosphocreatine (PCr).
Creatinine: Is the anhydrous form of creatine and formed in muscles by
nonenzymatic dehydration of creatine
- Creatinine is excreted in urine. It is one of the kidney function tests.
- Elevated creatinine levels in blood than normal indicates renal disease.
-Normal creatinine levels: 0.8- 1.2 mg/dl.
-II- Glycine participates in detoxification reactions in the body. It detoxify
aromatic acids such as benzoic acid (toxic) converting it into hippuric acid (less
toxic) which is excreted in urine.
Conversion of aromatic acids into specialized products
1- Phenylalanine amino acid
Essential amino acid
Converted into tyrosine (major pathway )
Minor pathway of phenylalanine:
occurs normally in liver tissues via transamination giving
phenylpyruvate (a metabolite with minor significance)
transaminase
Phenylketonuria (PKU):
PKU is a genetic disease caused by a defect in the gene responsible for
synthesis of PAH enzyme (97% of cases) or by deficiency of the BH4
cofactor (3%). As a result phenylalnine not converted into tyrosine and
accumulated in blood, tissues and brain. Phenyl pyruvate (a minor
metabolite of phenyalanien will also acumulate and secreted in urine
hence the name of the disaese, phenylketonuria).
Symptoms of PKU:
-Excess phenylalanine leads to mental retardation and delay in
growth, talking and walking.
-Hypopigmentation
(light hair, skin and eye) is also present
because tyrosine is not synthesized. Tyrosine is important for
synthesis of melanin pigment, so no tyrosine , no melanin.
-Musty odor of urine due to excess phenylalanine and
phenylyruvate
-Treatment of PKU
- Diet low in phenylalanine
- Aspartame (artificial sweetening agent) is contraibndicated
because it contain phenylalanine
2-Tyrosine
-Non essential: as it is synthesized in body from phenylalanine:
BH4
(PAH)
BH4= tetrahydrobioptrine . It is the cofactor for all aromatic amino acid hydroxylases ( i.e
cofactor for phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase).
Functions of tyrosine: tyrosine enter in the synthesis of:
1- catecholamines
2- melanin pigment
3- thyroid hormones
1- Catecholamines: dopamine, epinephrine and nor epinephrine
Epinephrine and nor epinephrine are secreted from adrenal medulla
in response to fear, stress, anger, low blood glucose and
hypotension. They stimulate degradation of glycogen and TAG
(stimlate glycogenolysis and lipolysis).
Synthesis of catecholamines
also called
tyrosinase
↓ tyrosinase
2-Synthesis of melanin:
Melanin is aromatic
quinone. It is black or
brown pigment present
in skin, hair and eyes. Its
function is to protect
underlying cells from the
harmful effects of sun
light ( UV radiation).
↓ tyrosinase
→ dopachrome →→ Melanin
dopaquinone
Albinism: Genetic disease due to
genetic
deficiency
of
tyrosinase
enzyme and lack of melanin synthesis.
This leads to hypopigmentation of skin,
hair and eyes making the albino are
sensitive to sun light (photophobia),
increasing the incidence of skin burns
and cancer.
3- Synthesis of thyroid hormones (T3 and T4):
- Tyrosine +I2 gives monoiodotyrosine (MIT) and diiodotyrosine (DIT)
- one MIT + one DIT gives T3
- 2 DIT gives T4 (structures not required)
Tryptophan amino acid
- Essential amino acid
- Both glucogenic and ketogenic (gives pyruvate and
Acetyl CoA).
Functions:
1- Synthesis of serotonin (5-hydroxy tryptamine) in gut, CNS, platelets
(BH4)
THB= BH4 (tetrahydrobioptrine)
AAAO= aromatic amino acid decarboxylase
Serotonin is a neurotransmitter, vasoconstrictor. Regulate mood and sleeping.
Its deficiency lead to depression. It is used as antidepressant
Research found that fruits (like dates, banana and papaya), turkey, peanuts, almonds,
green leaves increase the synthesis of serotonin
Serotonin is popularly thought to be a contributor to feelings of
well-being and happiness.
Approximately 90% of the human body's total serotonin is
located in the intestine, where it is used to regulate intestinal
movements. The remainder is synthesized in neurons of the
CNS, where it has various functions. These include the
regulation of mood, appetite, and sleep. Serotonin also has some
cognitive functions, including memory and learning. Increasing
serotonin is the mechanism of action of several classes of
antidepressants.
2- Synthesis of melatonin:
Melatonin is N-acetyl 5-methoxy tryptamine
-
↓↓
1) N-acetylation
2) O-methylation
Synthesis and secretion of melatonin is regulated by dark/light cycle. Production of
melatonin by the pineal gland in brain is inhibited by light and stimulated by darkness.
For this reason melatonin has been called "the hormone of darkness.
- Melatonin is sleep-inducing molecule
-So ingestion of food rich in tryptophan leads to sleepiness.
It is powerful antioxidant
It has important role in protecting skin from damaging effect of UV radiation:
3- Synthesis of nicotinic acid (niacin)
- Niacin (vitamin B3) is a member of vitamin B complex.
-Coenzyme NAD and NADP are derived from niacin.
NAD (to remember the
structure, not required)
- Niacin is important for skin health, regulate
intestinal movement and energy production
particularly in brain (because NAD and
NADP are imprtant cofactors in glycolysis)
- Deficiency of niacin leads to pellagra
(dermatitis, diarrhea and Dementia).
Insomnia and high sensitivity to sunlight.
- Pellagra occurs also in case of deficiency of
dietary tryptophan which converted into
niacin
- Pellagra occurs in areas where people eat
mainly maize (corn, the only grain low in
digestible niacin)