Biochem

Question 1

Functions of porphyrin

Answer 1

Oxygen transport in hemoglobin and myoglobin

Electron transport in cyrochrome a,b,c

Breakdown of peroxide as catalase

Hydroxylation in cytp450

Light absorption in chlorophyll

Question 2

Porphyrin structure

Answer 2

4 pyrrole
Carbon bridges
Metal ion in center
Propionate and methyl attached

Question 3

Metal Ion in porphyrin in hb

Answer 3

Iron

Question 4

Metal Ion in porphyrin in chlorophyll

Answer 4

Magnesium

Question 5

Forms of iron

Answer 5

Heme Fe2+ - ferrous

Hemin Fe3+ - ferric

Question 6

Heme synthesis overview

Answer 6

In mitochondria :
(I)
Succinyl coa + glycine —> delta-aminolevulinic acid
Enzyme : ALA synthase

In cytosol

(II)
2 Delta aminolevulinic —> porphobilinogen
Enzyme : ALA dehydrogenase

(III)
Porphobilinogen —-> uroporphyrinogen I or III
Enzyme : HMB synthase

(IV)
Uroporphyrinogen I and III —> coproporphyrinogen I and III
Enzyme : uroporphyrinogen decarboxylase

In mitochondria
(V)
coproporphyrinogen III —> protoporphyrinigen IX
Enzyme : coproporphyrinogen oxidase

(VI)
Protoporphyrinogen IX—> protoporphyrin IX
Enzyme : protoporphyrinigen oxidase

(VII)
Protoporphyrin IX —-> heme
Enzyme : ferrochelatase

Question 7

Rate limiting step of heme synthesis

Answer 7

Ala synthase

Question 8

Form of control of ALA synthase

Answer 8

Transcriptional regulation
Heme and hemin repress transcription of enzyme

Coordination with glob in chain synthesis

Allosteric inhibition by heme and hemin

Inducers of enzyme : aromatic drugs, xenobiotics, steroids

Question 9

Enzymes that can get deactivated by lead and other heavy metal

Answer 9

Ala dehydratase

Ferrochelatase

Question 10

What enzyme is bifunctional in heme synthesis

Answer 10

HMB synthase

Uroporphyrinogen I and III synthase activity

Question 11

What reaction in heme synthesis requires cysteine and ascorbic acid as reducing agents

Answer 11

Ferrochelatase

Question 12

Iron deficiency impact on ferrochelatase

Answer 12

Insertion of zinc leading to zinc protoporphyrin - used clinically to determine iron deficiency

Question 13

Porphyria

Answer 13

Hereditary or acquired defects in heme synthesis

Mostly autosomal dominant

Question 14

Exception in porphyria that is autosomal recessive

Answer 14

Congenital erythropoietic porphyria

Question 15

Location of porphyria in body

Answer 15

Hepatic or erythropoietic

Question 16

2 major locations of heme synthesis

Answer 16

Liver

Bone marrow

Question 17

Lead poisoning

Answer 17

Inhibit ferrochelatase and ALA
Dehydratase

Coproporphyrin III and ALA accumulates in urine

Question 18

Symptoms of lead poisoning

Answer 18

In children : 
Developmental defects 
IQ drop
Hyperactivity 
Insomnia 

Adults:
Severe abdominal pain
Mental confusion

Question 19

Acute intermittent porphyria

Answer 19

HMB synthase defect

porphobilinogen and ALA accumulations in Uribe

Dark urine in light and air
NO photo sensitivity

Question 20

Congenital erythropoietic porphyria

Answer 20

Uroporphyrinogen III synthase defect

Accumulation of uroporphyrinogen I and coproporphyrinogen I in urine

PHOTOSENSITIVITY

Question 21

Porphyria cutanea tarda

Answer 21

Uroporphyrinogen decarboxylase deficiency

Uroporphyrin accumulates in urine

PHOTOSENSITIVE

Question 22

Most common form of porphyria

Answer 22

Porphyria cutanea tarda

Question 23

Hereditary coproporphyria

Answer 23

Coproporphyrinogen oxidase deficiency

Intermediates before this block accumulate in urine

PHOTOSENSITIVITY

Question 24

Variegated porphyria

Answer 24

Protoporphyrinogen oxidase deficiency

Intermediate before block accumulate

PHOTOSENSITIVITY

Question 25

Erythropoietic porphyria

Answer 25

Ferrochelatase deficiency Protoporphyrin accumulate in erythrocytes, plasma and bone marrow PHOTOSENSITIVITY

Question 26

Where do you find most heme

Answer 26

RBC (85%)

Question 27

Component formed after heme degradation

Answer 27

Biliverdin which forms bilirubin

Question 28

How is bilirubin transported

Answer 28

By serum albumin

Question 29

Excretion of bilirubin pathway

Answer 29

RBC with heme RBC with heme degraded and release of bilirubin Bilirubin transported by albumin to liver Bilirubin in liver conjugated with glucuronic acid Bile formed excreted into small intestine In intestine , bacteria remove glucuronic acid and bilirubin is converted to urobilinogen One part of urobilinogen is converted to stercobilin and excreted through feces Other part of urobilinogen reabsorbed from gut and enter portal blood Some of it also do enterohepatic cycle Rest of it transported to kidney and converted to yellow urobilin and excreted in urine

Question 30

Types of jaundice

Answer 30

Hemolytic jaundice obstructive jaundice hepatocellular jaundice jaundice in newborns

Question 31

Hemolytic jaundice

Answer 31

Massive hemolysis of red blood cell leads to more bilirubin than can be processed More unconjugated bilirubin in blood which can’t be excreted so form jaundice

Question 32

Obstructive jaundice

Answer 32

Obstruction of bile duct (Tumors, bile stones) ``` Lead to nausea pain Pale clay colored stools liver damage increase in conjugated Bilirubin ```

Question 33

Hepatocellular jaundice

Answer 33

``` Liver damage (cirrhosis, hepatitis) Cause increased bilirubin level in blood due to decreased conjugation ``` Decreased urobilinogen so urine is dark and stool is pale High AST And ALT level due to liver damage Nausea Anorexia

Question 34

Jaundice in newborns

Answer 34

Premature babies have low expression of bilirubin glucuronyltramsferase So excess bilirubin Can cause toxic encephalopathy Treatment with blue fluorescent light ( conversion of bilirubin to polar version)

Question 35

Crigler naijar syndrome

Answer 35

Deficiency in bilirubin glucuronyltramsferase

Question 36

Gilbert’s syndrome

Answer 36

Liver does not properly process bilirubin due to defect in enzyme for conjugation. Overall mild Light eye jaundice

Question 37

Techniques to determine bilirubin concentration

Answer 37

Van den bergh réaction REaction when unconjugated bilirubin in aqueous solution Reaction when unconjugated or conjugated in methanol => gives total bilirubin CAn substract one from the other to find unconjugated bilirubin