Carbohydrate Metabolism Flashcards
Once Glucose is converted to Glucose-6-P what pathways can it enter?
- Glycolysis
- Pentose Phosphate Shunt
- Glycogenesis
Which enzyme is needed to commit glucose 6-P to glycolysis?
PFK-1
What are the enzymes of the three irreversible reactions are also the main regulated enzymes of glycolysis
hexokinase and glucokinase
PFK-1
pyruvate kinase
What reaction does Hexokinase catalyze?
glucose to glucose-6-phosphate
Hexokinase is found in the
muscle
When cellular concentrations of glucose-6-P rise above ordinary, Hexokinase is temporarily _____________ to bring the rate of glucose-6-P into balance with its rate of utilization
inhibited
- IT IS SENSITIVE TO NEED - DO WE NEED THAT GLUCOSE?
What reaction does PFK-1 catalyze?
phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate
what binds to the PFK-1 allosteric site to inhibit it?
ATP
what happens when ATP inhibits PFK-1 by binding to an allosteric site?
- Lowers the affinity of the enzyme for fructose-6-P
- AMP and ADP relieve the inhibition of PFK-1
why do AMP and ADP relieve the inhibition of PFK-1
As ATP is used, AMP and ADP begin to build up - therefore high levels of these tell the cell that more ATP needs to be made
high levels of what also inhibit PFK-1?
High citrate levels inhibit PFK-1
High citrate serves a signal that the cell is meeting its current needs for energy
what are the three ways that PFK is allosterically regulated?
- ATP - inhibit
- Citrate - inhibit
- Fructose 2,6-biphosphate - activate
what is the most significant allosteric regulator of PFK-1?
Fructose 2,6-bisphosphate
Fructose-2,6-bisphosphate enhances the ______ of PFK-1 for fructose-6-P. What does this stimulate?
affinity
Stimulates glycolysis
Inhibits FBP-1, slowing gluconeogenesis
what is a key intermediate in the CAC?
Citrate
Fructose 2,6-bisphosphate is formed by phosphorylating Fructose-6-P, catalyzed by ____________________
phosphofructokinase-2 (PFK-2)
What reaction does pyruvate kinase catalyze?
the direct transfer of phosphate from phosphoenolpyruvate (PEP) to ADP to produce ATP and pyruvate.
Pyruvate kinase is allosterically regulated by: Inihibtion (3)
- ATP
- Acetyl-CoA
- Fatty acids
Pyruvate kinase is allosterically regulated by: Activation (1)
Fructose 1,6-bisphosphate
Glycolysis is regulated hormonally by ______ and _________
insulin and glucagon
_________ promotes the transcription of glucokinase, phosphofructokinase-1, and pyruvate kinase
Insulin
________ reduces the expression
of glucokinase, PFK-1, and pyruvate kinase
Glucagon
______, _________, and ________ are converted into
glycolytic intermediates
Fructose, Mannose, and galactose are converted into
glycolytic intermediates
Which monosaccharide is metabolized faster,
glucose or fructose, why?
fructose
- can be more readily made into fat
Pyruvate can be converted either to: (3)
A) acetyl CoA - enter into CAC
B) Oxaloacetate - enter into GNG
C) Lactate (Cori cycle)
_________ is an allosteric activator of pyruvate carboxylase
Acetyl CoA
What reaction does FBP-1 catalyze?
catalyzing the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate
FBP-1 is allosterically inhibited by (2)
- Allosterically inhibited by AMP
- Allosterically inhibited by Fructose 2,6-bisphosphate
FBP1 is found in the
liver
FBP2 is found in the
muscle
Gluconeogenesis is regulated hormonally by
insulin and glucagon
Glucagon promotes _________ of FBP-2, lowering levels of Fructose-2,6bisP
activation
Glucagon can also induce the transcription of
PEP carboxykinase
Once Glucose is converted to Glucose-6-P which pathways can it enter
- Glycolysis
- Pentose Phosphate Shunt
- Glycogenesis
Which enzyme is needed to commit glucose-6-P to glycolysis?
hexokinase
The pentose phosphate shunt generates two main products:
- NADPH
- Ribose-5-Phosphate (“pentose phosphates)
Also generates Fructose-6-Phosphate and glyceraldehyde3-Phosphate, which can feed back into glycolysis
what are the two phases of the Pentose Phosphate Shunt?
Oxidative - Irreversible reactions
Non-oxidative - Reversible reactions
During the oxidative phase, the reaction
Glucose-6-phosphate -> Ribulose-5-phosphate generates…
Generates 2 NADPH
what are the functions of the oxidative phase? (2)
Functions:
- Fatty acid synthesis – more to come next week
- Reduces glutathione (antioxidant)
Glutathione is an __________. It is a 3 amino acid peptide made up of _______ - _______- ________
Glutathione is an antioxidant
Glycine-cystine-glutamate
_________ regenerates glutathione by replacing the donated H’s
NADPH
Pentose Phosphate Shunt is important when converting carbs to fat
what neutralizes (reduces) hydrogen peroxide to water by donating H’s. NADPH will then regenerate _________ by replacing the donated H’s
Glutathione
what enzyme is involved in Glucose-6-phosphate -> Ribulose-5-Phosphate
glucose-6-Phosphate dehydrogenase (G6PD)
what is the rate-limiting step of the oxidative phase?
Glucose-6-phosphate -> Ribulose-5-Phosphate
how is the oxidative phase regulated?
Regulated by ratio of NADPH:NADP+
- High NADPH: NADP+ ratio inhibits G6PD
- Also inhibited by high levels of Acyl CoAs
- Upregulated by insulin
G6PD deficiency is an X-linked trait. Is it more common in men or women?
men
What do you suppose Ribose-5-P can be used for?
R5P and its derivatives serve as precursors to many biomolecules, including DNA, RNA, ATP, coenzyme A, FAD (Flavin adenine dinucleotide), and histidine
During the non-oxidative phase, what is ribulose-5-P converted to?
Ribose-5-P OR into glycolytic
intermediates
Glucose is stored in polymeric form as glycogen
mostly in the _____ and ___________.
Glucose is stored in polymeric form as glycogen
mostly in the liver and skeletal muscle
muscle cells can use glucose directly BUT
the liver does not use this glucose
High glucose/energy levels will trigger _______
synthesis
glycogen - Glycogenesis
Glucose is transferred onto a growing chain of
glycogen as ____-glucose. Is this reversible or irreversible?
UDP
irreversible
UDP-glucose is added to an existing strand of
glycogen by the enzyme ________________
glycogen synthase
Glucose is added to the non-reducing end in what type of link?
alpha 1-4
_________ catalyzes the transfer of 4-8 glucose residues to a branch point
Branching enzyme
The branching enzyme is also called amylo-α(1,4->1,6)
glucosyl transferase
Glycogen synthase cannot initiate a new glycogen
chain de novo, it requires a
primer
Primer contains pre-formed (alpha1-4) polyglucose
chain with at least ___ glucose residues
4-8
what enzyme contains the primer and the enzyme needed to build the primer for glycogen synthesis (glycogenesis)
glycogenin
Glycogenolysis is a ________ progress. It is the _______ of glycogen into glucose units. Where does this occur?
catabolic
Breakdown of glycogen into glucose units
Occurs in the liver and muscle
Glucose is removed from the non-reducing ends of glycogen by the enzyme
Enzyme: glycogen phosphorylase
A de-branching enzyme has two functions:
1) transfers the outer 3 glucose residues from the branch to another non-reducing end (leaving only 1 reside behind at the branch point)
- Aka Oligo-α(1,4)-α(1,4)-glucotransferase
2) Removes the final glucose residue in the alpha(1à6) linkage
Aka Amylo-α(1,6)-glucosidase
Glucose-1-P is converted to glucose-6-P by the enzyme. Hint this is the same enzyme we saw in the firs step of glycogenesis
Enzyme: phosphoglucomutase
The liver can then convert glucose-6-P into glucose
with the enzyme _____? Hint: This enzyme catalyzes the third bypass reaction of gluconeogenesis
glucose-6 phosphatase (G6Pase)
which is expressed only in the liver, kidneys, and intestine
Muscles do not have this enzyme, why? What does the muscle do with glucose-6-P instead?
because they are not going to be releasing glucose
glycogen phosphorylase
Glycogen _______ and glycogen __________ are the two regulated enzymes in glycogen metabolism
Glycogen synthase and glycogen phosphorylase
Glycogen synthase regulation - allosterically activaited by
glucose-6-P
Glycogen phosphorylase regulation - Allosterically inhibited by? (2) and activated by _____ in the muscle only
inhibited by:
* Glucose-6-P
* ATP
* Free glucose (in the liver only)
activated by AMP (muscle only)
Glycogen synthase and glycogen phosphorylase can
also be regulated by ________ modification
covalent
Glycogen synthase is _________ by phosphorylation
de-activated
Glycogen phosphorylase is _________ by phosphorylation. What protein catalyzes this phosphorylation?
activated
Phosphorylation is catalyzed initially by the same protein,
protein kinase A (PKA)
