19-11-13 conversion of aa into products

8/12/2019 19-11-13 Conversion of Aa Into Products

1/27

Specialized products formed

from amino acids

19-11-13

Dpt 4thsemester


2/27

PORPHYRIN METABOLISM

Porphyrinsare the cyclic compounds formed byfour pyrole links through methenyl bridges

metalloporphyrin

In humans the most common metaloporphyrin isheme, consist of one ferous Fe+2 ion

Heme acts as prosthetic group for severalmolecules


3/27

Structural features are

1)Side chains: porphyrias vary due to natureof side chain attached to four pyrole rings

Uroporphyrincontains acetate and propionate

(A,P) side chainsCoproporphyrin contains methyl and

propionate groups (M,P)

Protoporphyrin IX (heme) contains vinyl, methyland propionate groups (V,M,P)


4/27

2) Distribution of the side chain: side chain of

porphyrins can be arranged around

tetrapyrrole nucleus in four ways designated I

to IV

Only type III porphyrin is physiologically

important in humans which is asymmetric


5/27


6/27

Biosynthesis of heme

Major sites for the synthesis of heme are liverand erthrocytes. About 85% of heme is

synthesized in erythoid tissue

The initial and last three steps of porphyrin

synthesis occurs in mitochondriawhile the

intermediate steps occur in cytosol


7/27

Formation of -aminolevulinic acid

(ALA)


8/27

More the porphyrin production more will be

the heme (hemin) which decreases ALAS1

Drug administration will increase ALAS1

activity thus increasing heme consumption so

heme would become lower which will

increase ALAS1


9/27

Formation of porphobilinogen

byALA-dehydratase.


10/27


11/27


12/27

So

Porpho-uro-copro-proto-protoporphyrin IX


13/27

Porphyrias result due to deficiency of any

enzyme in the heme synthesis pathway

Causes increased accumulation & excretion of

porphyrins

Purple pigment appeared in urine of patients

porphyrin

hepatic

acute chronic

erthyropoietic


14/27

individuals with enzyme defects priorto the

tetra pyrrol formation will show abdominal

and neurophysiatric signs while

Individuals showing enzyme defects leadingto

pyrrole formation shows photosensitivity


15/27

Hepaticporphyrias

chronic

Deficiency of

uroporphyrinogen

decarboxylase

iron overload,

photosensitivity,hepatitis B,C, HIV

infections

acute

ALA dehydratasegastointestinal,

neurophysiatricattacks


16/27

Erthyroid porphyria: deficiency of

Ferrochelatase

VARIEGATE PORPHYRIA deficiency in

Protoporphyrinogen oxidase

HEREDITARY COPROPORPHYRIAdeficiency in

Coproporphyrinogen oxidase


17/27

Treatment of porphyrias

Symptoms of porphyrias can be diminished by

ingestion of glucoseand heminwhich

decreases the synthesis of ALAS1

Sunlight avoidanceand -carotene are also

helpful for treatment


18/27

Heme degradation


19/27

Solubility in hepatocytes increasedby addition

of two molecules of glucuronic acid

(conjugation)

Reaction catalysed by bilirubin glucuronyl

transferase

Deficiency of this enzyme results in Crigler-

Najjar I & Gilbert syndrome


20/27


21/27


22/27

Jaundiceis characterized by excess

accumulation of bilirubin in blood

Symptoms are yellowing of nail beds, scleraand skin colour

Types of jaundice

a) hemolytic

b) hepatocellular

C) obstructive

In new borns hepatic bilirubin glucoronyl

transfeaseis low at birth


23/27

Other nitrogen containing compounds Catecholamines: epinephrine, nor

epinephrine,dopamine collectively called

neurotransmitters


24/27

Histamine allergic and inflammatoryreactions, gastric acid secretion, and possibly

neurotransmission


25/27

Serotonin has multiplephysiologic roles, including pain perception, regulation

of sleep,appetite, temperature, blood pressure


26/27

Creatine Creatine is a high energy reserve, rapidly

provides ADP to maintain ATP during muscle

contraction.


27/27

Melanin

synthesized from tyrosine in the epidermiis

Its function is to protect cells from the

harmful effects of sunlight Defect in Cu containing tyrosinasecauses

albinism

19-11-13 conversion of aa into products

Documents