Carb 2 Flashcards
(54 cards)
HMP pathway terms, sites
Hexose monophosphate
Pentode phosphate pathway
Dicken Horecker pathway
Cytosol
Oxidative phase in fat,steroid,… synthesis and in lens, RBC,…
First step of HMP pathway
G-6-P to 6-PhosphoGluconate by G-6-PD
NADPH is produced
Irreversible
RDS
Production of Ribulose
6-PhosphoGluconate is decarboxylated by 6-PhosphoGluconate Dehydrogenase to Ribulose-5-P
NADPH is produced
Free radical scavenging by NADPH
H2O2 is converted to H2O by glutathione peroxidase
The oxidised glutathione is then converted back by glutathione reductase with NADPH and FAD
Required for transparency of lens ,Hb and RBC
Reactions of the non oxidative (reversible) part of HMP pathway
Ribose-5-P (from epimerase)
reacts with Xylulose-5-P
(from ketoisomerase)
5+5=3+7=4+6
Then 4+5=3+6 ( F-6-P)
The 2 F-6-P will form G-6-P
And the glyceraldehyde-3-P will form one half G-6-P
The remaining are 3 CO2
Reaction having trans ketolase and those having transaldolase
Transketolase 5+5=3+7
Then 4+5=3+7
Transaldolase
3+7=6+4
G-6-PD deficiency,the most common enzyme deficiency
NADPH decreases
Haemolytic anaemia and jaundice
Methemoglobinemia
Sulfa drugs, primaquine (anti-malarial), Fava beans (favism) aggravates this
Heinz bodies in RBC
G-6-PD deficiency is common in Africa because
The lifespan of RBC is too low for Plasmodium falciparum to complete its life cycle
Wernickes Korsakoff’s syndrome
Thiamine deficiency
Transketolase will be deficient
Enzymes involved in phosphorylation then UDP transfer of galactose
Galactokinase
Then galactose-1-P Uridyl transferase (GALT)
converts it into UDP galactose
(producing G-6-P as by product)
An epimerase can be used to convert UDP Galactose back to UDP Glucose
Classic galactosemia
GALT defect
Galactose 1 P increases, which is an inhibitor of glycogen phosphorylase
Leading to decreased glycogenolysis
Fasting hypoglycaemia (especially as the child vomits and has feeding difficulty)
Non classic galactosemia
Galactokinase or
Epimerase
Symptoms of classic galactosemia
Age of onset at 1-2 weeks (milk)
- Failure to thrive, vomiting, feeding difficulty
- seizures, coma, mental retardation
- Hepatomegaly, liver failure ,jaundice
- galactitol/ dulcitol (oil-drop cataract)
- Neonatal sepsis (E coli)
Diagnosis of classic galactosemia
Benedictus test Glucose oxidase test -ve Galactose tolerance test (should not be done) Music acid test Enzyme/ genetic mutation studies
Treatment of classic galactosemia
No breast feeding
Lactose free diet up to 4-5 years ( as an enzyme Gal-1-P pyrophosphorylase which converts Gal-1-P to less toxic galactose)
Why does fructosemia does not exist
Because the renal threshold level for fructose is too low for it to be manifested
Instead only fructosuria occurs
Difference between fructokinase and hexokinase
Fructose is converted to fructose-1-P by fructokinase, bypassing PFK and then split by aldolase B to glyceraldehyde ( not 3 phosphate) and DHAP
Glyceraldehyde is later phosphorylated by kinase
Fructose and diabetes
Hyperlipidemia
Hyperuricemia (gout)
Essential fructosuria
Deficiency of fructokinase
No fructosemia
Benign
No manifestations
Hereditary fructose intolerance
Deficiency of aldolase B
Inhibits glycogen phosphorylase which inhibits glycogenolysis
Leads to fasting hypoglycaemia
(Convulsions, coma)
Clinical features of Hereditary fructose intolerance
Weaning leads to onset of the disease
Vomiting, feeding difficulties, failure to thrive
Liver failure,hepatomegaly, jaundice
No cataract, because no fructose accumulation
Diagnosis of hereditary fructose intolerance
- Benedicts test +ve, but glucose oxidase test -ve
- Rapid furfural test
Seliwanoffs test - Gene and enzyme studies
Enzymes of first part of Krebs cycle (upto succinyl CoA)
- Citrate synthase
- Aconitase
- Isocitrate dehydrogenase ICDH (mitochondrial)
- Alpha keto glutarate dehydrogenase
Special features of aconitase
- Contains Fe+2
2. Moonlighting enzyme , as it takes part in iron homeostasis
