Topic 6 Flashcards
How is galactose metabolised?
initially by galactokinase into galactose- 1P
this is then metabolised by uridyl transferase back into the glucose- 1P for the glycolysis pathway
UDP- galactose epimerase converts UDP-Galactose (converted from UDP- glucose which converts to glycogen as well) to Galactose- 1P
What is galactosaemia?
a deficiency in any of the three enzymes that metabolise galactose can cause galactosaemia
this is where you are unable to utilise galactose
Galactokinase deficiency (rare)- galactose accumulates Transferase deficiency (common)- galactose and galactose- 1P accumulate
treatment is to stop including lactose in the diet
Why is accumulating galactose a problem?
Galactose enters other pathways which can deplete NADPH
for example,
in the eyes, it depletes the lens of NADPH causing the structure to be damaged causing cataracts
it is not known why the accumulation of galactose- 1P affects the liver, kidneys and the brain
Explain how galactosaemia works
the raised galactose conc enters new pathways
this depletes the NADPH levels as NADPH is used in the reaction of galactose to galactitol
this prevents maintenance of free sulphydryl groups on proteins
there is therefore inappropriate disulphide bone formation occurring leading to loss of structural and functional integrity of some proteins that depend on free sulphydryl groups
What is the pentose phosphate pathway?
two stage pathway- cytoplasmic
first step is oxidative decarboxylation:
- glucose-6P converts to 5 carbon sugar and carbon dioxide by glucose-6P dehydrogenase
- NADPH is produced from NADP+ in this step
second step is rearrangement to glycolytic intermediates:
- 3 x 5 carbon sugars converted to 2 fructose- 6P and 1 glyceraldehyde- 3P
- there is no ATP production
- there is a loss of carbon dioxide so the pathway is irreversible
- it is controlled by NADP+ / NADPH ratio at G6P dehydrogenase
What are the functions of the pentose phosphate pathway?
- produce NADPH in cytoplasm, used for:
- biosynthetic reducing power
- maintaining free sulphydryl groups (cysteine) groups on certain proteins; prevents oxidation to disulphide bonds - produce C5 sugar for nucleotides needed for nucleic acid synthesis
- therefore high activity in dividing tissues
What happens with a glucose-6-phosphate dehydrogenase deficiency?
as the pentose phosphate pathway has an important role in providing NADPH to maintain the SH group of proteins in a reduced state, structural integrity and functional activity of some proteins will be lost as NADPH will levels will decrease
G6PDH deficiency is very common inherited defect
can affect the lens of the eye- cataracts form
What is the rate limiting enzyme?
glucose 6 phosphate dehydrogenase
What is allostery?
activator or inhibitor binds at another site and changes the activity of the enzyme
What is covalent modification?
the introduction of bulky negatively charged phosphate group which alters the structure which alters the activity
What are the principles of metabolic pathway regulation?
the irreversible steps are potential sites of regulation, reversible steps are not regulated
reduced activity reduces the influx of substrates through the pathway directly which reduces the levels of product
for reversible steps, even when inhibited they still reach equilibrium so levels of product not affected
What is feedback inhibition?
allosteric inhibition by end pathway product on first enzyme in pathway ( non branched pathway )
this reduces the entry of substrate and build up of intermediates in the pathway
What is the importance of the committing step?
inhibition of the committing step allows substrate to be diverted into other pathways
Explain the regulation of catabolic pathways as an example
these pathways are inhibited by high energy signals and stimulated by low energy signals
What is hormonal regulation?
the hormone binds to its receptor on the enzyme and activates signalling pathway
protein kinase or protein phosphatase activated
PK causes phosphorylation of the enzyme, PP causes dephosphorylation of the enzyme
both can alter the protein activity positively or negatively depending on the enzyme the hormone binds to
