W6 Other Pathways of Carbohydrate Metabolism Flashcards
what is the glyoxylate cycle
an anabolic variant of the TCA cycle (occur in plants)
main difference of glyoxylate cycle from TCA cycle
in TCA cycle, isocitrate undergoes two decarboxylation reactions via isocitrate dehydrogenase and alpha keto glutamarate dehydrogenase > succinate
but for glyoxylate cycle, isocitrate lyase cleaves isocitrate into succinate and glyoxylate > bypass decarboxylation reactions to preserve carbon
where does glyoxylate cycle take place
in glyxosome
summary of glyoxylate cycle
acetyl coA condenses with oxaloacetate to give citrate > isocitrate in TCA cycle
instead of being decarboxylated, isocitrate cleaved by isocitrate lyase into succinate and glyoxylate
glyoxylate condenses with another acetyl coA to form malate, catalysed by malate synthase > malate oxidised as in in the TCA cycle
succinate passes into mitochondrial matrix and enters TCA cycle to form malate
relationship between glyoxylate cycle and TCA cycle
reactions of glyoxylate cycle proceed simultaneously with that of TCA cycle as intermediates pass between these compartments
succinate produced from isocitrate via isocitrate lyase can be transferred to mitochondria > fumarate > malate > oxaloacetate
what are the two pathways that malate can take once its produced from succinate
stay in the TCA cycle to produce energy
or pass into cytosol > converted by gluconeogenesis into fructose-6-phosphate (precursor of sucrose)
why do plant seeds store fuel as lipids rather than carbohydrates
seeds should be lighter in weight for easier dispersion > lipids is 2-fold lighter than carbohydrates
where is NADPH dependent fatty acid synthesis located
in the cytoplasm
what is the pentose phosphate pathway
generates NADPH for reactions that require reducing equivalents (electrons) or ribose 5-P for nucleotide biosynthesis
5 carbon sugar intermediates of pathway are reversibly interconverted to intermediates of glycolysis
enzymes of this pathway are particularly abundant in the cytoplasm of liver and adipose cells
first step of pentose phosphate pathway
glucose-6-phosphate dehydrogenase oxidises aldehyde of glucose-6P at C1 and reduce NADP+ to NADPH > gluconolacctone
step 2 of pentose phosphate pathway
gluconolacctone rapidly hydrolysed to 6-phosphogluconate, a sugar acid with carboxylic acid group at C1, catalysed by 6-phosphogluconolactonase
definition of epimerisation and isomerisation
epimerisation: interchange of groups on a single carbon
isomerisation: interchange of groups between carbons
step 3 of pentose phosphate pathway
carboxyl group is released as CO2, with electrons transferred to NADP+ > produce NADPH and CO2, forming ribulose-5-phosphate
reaction catalysed by 6-phosphogluconate dehydrogenase
in first 3 steps, total of 2 NADPH formed per mole of glucose-6-phosphate
step 4 of pentose phosphate pathway
ribulose-5-phosphate converted into ribose-5-phosphate (R5P) via isomerisation catalysed by ribulose-5-phosphate isomerase
step 5 of pentose phosphate pathway
ribulose-5-phosphate epimerase catalyse conversion of ribulose-5-phosphate into xylulose-5-phosphate (Xu5P)
enzymes involved in non oxidative portion of pentose phosphate pathway
epimerise, isomerase, transketolase and transaldolase
step 6 of pentose phosphate pathway
transketolase first reaction
transketolase catalyse transfer of 2 carbon units from Xu5P to R5P > produce glyceraldehyde-3-phosphate (GAP) and sedoheptulose-7-phoshate (S7P)
reaction requires cofactor TPP
step 7 of pentose phosphate pathway
transaldolase transfer 3 carbon unit from S7P to GAP > produce fructose-6-phosphate (F6P) and erythrose-4-phopshate (E4P)
this aldol cleavage occurs between the two OH carbons adjacent to the keto group
important step for regeneration of glycolic intermediates
step 8 of pentose phosphate pathway
transketolase second reaction
2 carbon unit from Xu5P transferred to E4P > produced F6P and GAP > both can enter glycolysis or gluconeogenesis
mechanism of TPP-dependent transketolase reaction
mechanism involves abstraction of acidic thiazole proton > attack by carbanion at carbonyl carbon of ketone phosphate substrate, expulsion of the GAP product and the transfer of the 2 carbon unit
what are the net products of metabolism of 3 mole of 5 RuBP
2 mole of F6P and 1 mole of GAP
what is regulation of pentose phosphate pathway controlled by
by cellular concentrations of NADPH, which is a strong inhibitor of G6P dehydrogenase
NADPH oxidised in other pathways > rate of G6P dehydrogenase increase to produce more NADPH
synthesis of liver G6P dehydrogenase is induced by increased insulin:glucagon ratio after carbohydrate meal
how is fructose converted to C3 molecules
fructokinase phosphorylates fructose with use of ATP into fructose-1-phosphate > cleaved by aldolase B into dihydroxyacetone-P (DHAP) and glyceraldehyde
dihydroxyacetone-P can enter glycolysis and be converted into GAP > pyruvate + TCA cycle or fatty acid synthesis
glyceraldehyde can be converted into GAP via trios kinase using ATP > sent into glycolysis > pyruvate > TCA cycle or fatty acid synthesis
role of pentose phosphate pathway in generation of NADPH
major source of NADPH > provide reducing equivalents for biosynthetic reactions and for oxidation-reduction reactions involved in protection against toxicity of reactive oxygen species (ROS)
uses of NADPH
maintain levels of reduced glutathione (GSH) for glutathione-mediated defence against oxidative stress
used for anabolic pathways: fatty acid synthesis, cholesterol synthesis and fatty acid chain elongation
source of reducing equivalents for cytochrome P450 hydroxylation of aromatic compounds, steroids, alcohols and drugs
found in phagocytic cells where NADPH oxidase uses NADPH to form superoxide from molecular oxygen > superoxide generates hydrogen peroxide > kills microorganism take up by phagocytic cells
what are the 3 irreversible steps in gluconeogenesis
conversion of pyruvate to phosphoenol pyruvate
conversion of fructose-1,6-biphosphate to F6P
conversion of glucose-6-phosphate to glucose
precursors of gluconeogenesis
amino acids (particularly alanine), lactate and glycerol
metabolism of gluconeogenic precursors
- conversion of lactate to pyruvate by lactate dehydrogenase, producing NADH
- alanine transferase transfers amino group of alanine to alpha ketoglutarate > glutamate > pyridoxal phosphate accepts and donate amino group > forms pyruvate
- conversion of glycerol to glycerol-3-phosphate by glycerol kinase using ATP > convert to DHAP by glycerol-3-phosphate dehydrogenase using NAD+
mechanism of pyruvate carboxylase to convert pyruvate to oxaloacetate
- ATP-dependent carboxylation of the cofactor to give N-carboxybiotin
- activated derivative transfers the carboxyl directly to pyruvate > produce oxaloacetate
pyruvate carboxylase uses biotin as cofactor, which is linked to elipson amino group of lysine which swings to transfer the carboxyl
why does gluconeogenesis require metabolic transport
pyruvate is converted to oxaloacetate in mitochondria but oxaloacetate cannot be transported across mitochondrial membrane
must first be reduced to malate > transported into cytosol > oxidised back into oxaloacetate before gluconeogensis can continue
known as malate-aspirate shuttle
how is pyruvate converted to phosphoenol pyruvate
- pyruvate converted to oxaloacetate în mitochondria by pyruvate carboxylase, requires atp and CO2
- oxaloacetate decarboxylated and phosphorylated by phosphoenolpryuvate carboxykinase > produce phosphoenol pyruvate, releasing CO2 and requiring GTP as main energy donor
**the same CO2 used that was fixed in step 1 is released in step 2 > no net fixation of CO2
how is fructose-1,6-biphosphate converted to fructose-6-phosphate
via hydrolysis using allosteric enzyme fructose-1,6-biphosphatase
citrate stimulates biphosphatase activity
fructose-2,6-biphosphatase and AMP are inhibitors of the biphosphatase
how is glucose-6-phosphate converted back to glucose
via glucose-6-phosphatase
reaction involves a phosphorylated enzyme intermediate, phosphohistidine
glucose-6-phosphatase present in membrane of ER of liver and kidney cells but absence in muscle and brain > gluconeogenesis not carried out in muscle and brain
net reaction of gluconeogenesis
2 pyruvate + 2 NADH + 2H+ + 4 ATP + 2 GTP + 6H2O > glucose + 2 NAD+ + 4ADP + 2 GDP + 6Pi
net free energy: -37.7kJ/mol
why can gluconeogenesis not be merely the reverse the glycolysis
glycolysis is exogenic of about -74kJ/mol > if gluconeogenesis is merely the reverse, would be strongly endogenic and cannot occur spontaneously
what are the two important regulators of gluconeogenesis
acetyl coA and fructose-2,6-biphosphate
