Lecture - Biochemical Synthesis 2

Question 1

What can you synthesize from glucose

Answer 1

• Sorbitol

- other polyols

Question 2

What can you synthesize from glucose 6 P

Answer 2

• Ribose

- NADPH

Question 3

Synthesis of sorbitol: polyol pathway

Answer 3

• glucose is in equilibrium between ring form and chain form
• chain form can undergo reduction bua aldose reductase
• leads to formation of sorbitol
• sorbitol can be converted back to fructose via Surbitol dehydrogenase but slow reaction

Question 4

Pentose phosphate pathway/shunt

Answer 4

• a key synthetic pathway from G6P
• an alternative fate for glucose
• leads to synthesis of ribose
• maintaining gluthathione (GSH) in recuded state
• GSH can protect cell proteins from oxidation
• reduces toxic radicals
• link back to glycolisis further down the pathway

Question 5

Pentose phosphate pathway

Answer 5

• G6P - G6P dehydrogenase -> ribulose 5-P -> Ribose 5P
• ribose 5 P can give rise to purine and pyriimidine
• ribulose 5 can also give rise to Xylulose 5P and go back to Fructose 6P and G3P

Question 6

Major consequences of Pentose phosphate pathway

Answer 6

• synthesis of ribose 5 phosphate: purine and pyrimidine
• synthesis of NADPH: key source of reducing power for cytoplasm
• provides independent control of ribose and NADPH synthesis

Question 7

Oxidation of glutathione: protection from pro-oxidants

Answer 7

2 GSH + ROOH -> GSSG + H2O + ROH

• ROOH toxic
• GSSG oxidized form
• GSH reduced form

Question 8

REgeneration of reduced gluthathione: role of NADPH

Answer 8

• GSSG + NADPH -> GSH

- so the pentose phosphate pathway supports regeneration of GSH by providing NADPH

Question 9

G6P dehydrogenase deficiency

Answer 9

• failure of NADPH synthesis
• impairs reduction of GSH and removal of toxic radicals
• also deficient in 6-phosphoglucono-delta-lactone

Question 10

Favism

Answer 10

• hemolytic crisis in an individual with G6P deficiency
• eryhtocytes are normally protected by GSH
• if GSH cannot be regenerateds cause lack of NADPH - > favism
• cell membrane damage
• more common in males (X linked)

Clinical features: acute ehemolysis, jaundice, anemia

Question 11

G6PD deficiency and malary

Answer 11

• G6PD deficiency protects from malaria

Question 12

Biosynthesis of heme

Answer 12

• metabolism starts in mitochondria with succinyl coA (4C)
• synthesis of aminolevulinic acid by combination of succinyl coA and glycine (uses ALA synthase)
• ALA is then exported to cytoplasm
• 2 ALA combine and PBG synthase forms PBG (release of 2 H2O)
• 4 PBG combine to form HMB
• HMB condenses and forms a cyclic structure: uroporphyrinogen III
• trimming + electon management -> protoporphyrin IX
• Ferrochelatase converst protoporphyrin to Heme (Fe in the middle)

Question 13

Prophyrias: disorders of heme biosynthesis

Answer 13

• one of the enzymes in the heme synthesis pathway is disrupted -> accumulation of porphyrin
• clinical features: main problem is with the accumulation of intermediates, not the heme deficiency

Question 14

Acute prophyris

Answer 14

• GI effects: nausea, vomiting, abdominal pain: autonomic neuropathy
• CNS effect: acute organic brain syndrome, seizures, coma
• Motor neuropathy

Question 15

Non acute/chronic porphyrias

Answer 15

• photosensitization

Question 16

Acute porphyrias

Answer 16

• aute intermittent porphyria: excess ALA and PBG

- variegate porphyria: Multiple metabolites in excess

Question 17

Chronic porphyria

Answer 17

• Porphyria cutanea tarda

- variegate porphyria