Glycogen, Gluconeogenesis Flashcards
(121 cards)
1
Q
how can glucose be regenerated to maintain homeostasis
A
1) from Glycogen breakdown
2) from Gluconeogenesis
2
Q
where does Glycogenolysis occur?
what does it go from and what is the end product
A
in liver and skeletal muscle
-catabolic pathways from glycogen to glucose-6-phosphate
3
Q
gluconeogenesis occurs in what organ(s) and when? why?
A
in the liver
between meals to keep brain (erythrocytes?) supplied with glucose
4
Q
what are 4 key features of gluconeogenesis
A
a) cannot make net glucose from acetyl-CoA
b) oxaloacetate is the starting material
c) carbon source is amino acid arising from protein
degradation
d) feed in via TCA cycle (e.g. α-ketoglutarate,
succinate, or pyruvate)
5
Q
what is the first step of glycogenolysis?
what enzyme is used?
what end of glycogen is reacted?
A
Removal of a terminal glucose residue from the nonreducing end of a glycogen chain by glycogen dephosphorylase:
6
Q
what kind of process is catalyzed by glycogen phosphorylase? when does it stop?
A
Primary rxn is cleavage of α1,4 glycosidic bond between 2 glucose
residues, using Pi instead of water (phosphorolysis); glucose is
cleaved from non-reducing end one unit at a time to yield
glucose-1-P and a chain shortened by 1 unit
-repetitive process
-enzyme removes
successive glucose
residues until it
reaches the 4th
glucose from the
branchpoint
7
Q
3 steps of glycogen breakdown
A
1) Glycogen phosphorylase can go up to 4 units from α1-6 branch pt
2) Debranching enzyme then transfers 3 glucose units to chain end
and single glu is hydrolyzed to free glu by same enzyme
3) Phosphoglucomutase now converts G-1-P to G-1,6-P to G-6-P
8
Q
how does phosphoglucomutase work
A
serine residue of enzyme phosphorylates C6 of glucose 1 phosphate to make glucose 1, 6 bisphosphate
serine phosphate replaced with OH temporarily
and serine then removes phosphate from C1 of transient glucose 1, 6 bisphosphate, yielding G-6-P
9
Q
what happens to G-6-P made from gluconeogensis:
in the muscles?
in the liver? Give details for this one.
What transporter does glucose use to leave the cell and when does this happen?
A
in muscles: G6P can enter glycolysis
in liver: G-6-P formed in cytosol is transported into ER by G6P transporter (T1) and hydrolyzed by glucose-6-phosphatase; resulting Pi and glucose carried back to cytosol by other transporters (Pi transporter AKA T3 and glucose transporter AKA T2, respectively)
-Glucose leaves hepatocyte via GLUT2 transporter, released into
blood when level drops (between meals)
10
Q
what general rxn makes a sugar nucleotide during the glycogen synthesis pathway?
what is the enzyme used?
describe the reaction.
A
sugar phosphate + NTP –> NDP sugar + PPi
enzyme: sugar pyrophosphorylase
-Formation of sugar nucleotide involves:
a) condensation rxn between NTP and sugar phosphate
-negatively charged oxygen on sugar phosphate serves as a
nucleophile, attacking α-phosphate of NTP and displacing PPi
-rxn is pulled in forward direction by hydrolysis of PPi
pyrophosphate hydrolysis drives rxn forward
PPi —> 2Pi
11
Q
What makes up UDP-Glucose
A
Uridine (base), ribose, diphosphates and a D-Glucosyl group
12
Q
glycogen synthase is affected in what disease
A
Type 0 Glycogen storage disease in liver
13
Q
what is type of disease is caused by a defect in G-6-phosphatase,
A
Type Ia (Von Gierke’s) Glycogen storage disease in liver
14
Q
what disease is caused by defect in Microsomal Pi transporter
A
Type Ic Glycogen storage disease in liver
15
Q
What type of disease is caused by defect in microsomal glucose-6-phosphate translocase
A
Type Ib Glycogen storage disease in liver
16
Q
What type of disease is caused by defect in Lysosomal Glucosidase
A
Type II (pompe’s) in skeletal and cardiac muscle
17
Q
What type of disease is caused by defect in debranching enzyme
A
Type IIIa (Cori’s or Forbes’s) in liver, skeletal and cardiac muscle
18
Q
What type of disease is caused by defect in Liver debranching enzyme (muscle enzyme is normal)
A
Type IIIb in liver
19
Q
What type of disease is caused by defect in Branching enzyme
A
Type IV (Andersen’s) in liver and skeletal muscle
20
Q
What type of disease is caused by defect in muscle phosphorylase
A
Type V (McArdle’s) in skeletal muscle
21
Q
What type of disease is caused by defect in liver phosphorylase
A
Type VI (Hers’s) in liver
22
Q
What type of disease is caused by defect in Muscle PFK-1
A
Type VII (Tarui’s) in muscle and erythrocytes
23
Q
What type of disease is caused by defect in Phosphorylase Kinase
A
Type VIb, VIII, or IX in liver, leukocytes and muscle
24
Q
What type of disease is caused by defect in Glucose transporter (GLUT 2)
A
Type XI (Fanconi-Bickel) in the liver
25
what happens during glycogenesis after UDP-Glucose is formed?
1) Glycogen synthesis: chain is elongated by glycogen synthase, which
transfers glu residue of UDP-glucose to non-reducing end of a
glycogen branch to make a new α1 4 linkage
2) Branch synthesis: glycogen-branching enzyme forms new branch pt
3) Further glu residues may be added to new branch by glyc.synthase
26
What is Glycogenin?
What is its role in glycogen?
What is the resulting structure of glycogen?
1) Glycogenin: primer by which new chains are assembled (preformed
a1 4 polyglucose chain or branch with at least 8 glu residues)
a) transfer of glu from UDP-glucose to OH-group of glycogenin
b) nascent chain extended by sequential addition of 7 more glucose
residues from UDP-glucose (a and b catalyzed by glycogenin)
2) Glycogen synthase further extends glycogen chain
3) Structure of glycogen particle: central glycogenin molecule, glycogen
chains (12-14 residues) extend in tiers (~55,000 glu residues)
27
What catalytic activity does Glycogenin have?
1. - glucotransferase activity: tranfers glucose from UDP-Glucose to hydroxyl oxygen on tyrosine residue
- releases UDP
2. - Chain extending activityadds glucose to non-reducing end of glycogen
- releases UDP
28
how many residues does each glycogen chain have?
12-14 glucose residues
29
how many residues of glucose in glycogen?
about 55,000 residues
30
how many glucose residues are added to glycogenin?
at least 8.
31
Why is gluconeogenesis important? what tissues depend on it?
```
Glucose from blood: sole
or major fuel source for
human brain and nervous
system, erythrocytes,
testes, renal medulla
(brain requires ~120g
glucose /day - more than
half of glycogen stored in
muscle and liver
```
32
define gluconeogenesis
Gluconeogenesis:”formation
of new sugar”; synthesis
of glucose from noncarbohydrate
precursors
33
What kind of substrates does gluconeogenesis use to make new glucose?
When does this occur?
-Converts pyruvate and
related 3C and 4C
compunds to glucose
when supply of glucose from
stored glycogen is
insufficient (i.e. between
meals, exercise,etc)
34
Where does gluconeogenesis take place primarily?
takes place mainly in the
| liver & kidney in mammals
35
what are the some general precursors for gluconeogenesis?
- lactate, pyruvate, glucogenic AA's (all these enter gluconeogensis through the TCA)
- triacylglycerols, glycerol
- Plants can utilize CO2 fixation to make 3-phosphoglycerate that enters gluconeogenesis
36
what can glucose 6 phosphate make? (anabolic products)
Blood glucose, glycogen, glycoproteins, Disaccharides, monosaccharides, other monosaccharides, starch, sucrose
37
how many reactions in glycolysis are reversible?
7/10
38
what makes the 3 glycolysis reactions irreversible?
what are these reactions?
-they have large negative delta G
-glucose to G-6P by hexokinase
-F6P to F16P by PFK1
-PEP to pyruvate by pyruvate
kinase
39
what rxns are used in gluconeogenesis to bypass irreversible rxns in glycolysis?
Are they reversible?
- Pyruvate to OAA (pyruvate carboxylase)
- Uses ATP
- biotin cofactor used
- OAA to PEP (PEP carboxykinase)
- Uses GTP
- F1,6BP to F6P ( Fructose-1,6-Bisphophatase)
- Uses H2O and releases Pi
- G -6-phosphate to glucose (Glucose 6 Phosphatase)
- Uses H2O and releases Pi
-”bypass” rxns are sufficiently
exergonic to be effectively
irreversible in direction of
glucose synthesis
40
where do gluconeogesis and glycolysis occur?
What does this lack of compartmentalization imply?
Both pathways occur in cytosol,
That the opposing pathways require reciprocal and
coordinated regulation
41
what energy molecules and reducing equivalents are used in gluconeogenesis?
Evaluate this cost.
4 ATP, 2 GTP, 2 NADH
Energetically expensive
42
What is pyruvate reacted with during gluconeogenesis?
In mitochondria, pyruvate is converted to
| OAA by pyruvate carboxyase (biotin-requiring; consumes ATP)
43
OAA in the cytosol makes what in gluconeogenesis?
OAA is converted to PEP by PEP carboxykinase; CO2 added in previous reaction is lost here as CO2 ; GTP acts as phosphoryl group donor; irreversible rxn
44
what is the role of biotin in pyruvate carboxylase?
Cofactor Biotin - flexible arms carry rxn
| intermediates CO2 between enzyme active sites
45
what path predominates when Lactate is starting substrate in gluconeogenesis?
give the path as is it shown in the diagram. Include cofactors
1) it is converted to pyruvate in the cytosol via LActate dehydrogenase (makes NADH + H+)
2) Pyruvate enters mitochondria and reacts with ATP via pyruvate carboxylase making OAA (biotin cofactor)
3) OAA reacts with GTP and is decarboxylated by mitochondrial PEP carboxykinase releasing CO2
4) PEP leaves mitochondria and continues in glycolysis
46
What path predominates when pyruvate in cytosol is starting substrate in glconeogensis (not from lactate take)
1) Pyruvate enters mitochondria and is carboxylated to OAA by pyruvate carboxylase (CO2 added)
2) OAA makes Malate via Mitochondrial malate dehydrogenase (MAkes NAD+)
3) malate leaves mitochondria and is made into OAA by cytosolic malate dehydrogenase (makes NADH)
4) OAA makes PEP via cytosolic PEP carboxykinase (releases CO2)
47
why does the starting substrate lead to a predominant pathway for that substrate in gluconeogenesis?
Path that predominates depend on the glucogenic precursor (lactate or pyruvate); when lactate is precursor, right path predominates because cytosolic NADH is generated in LDH rxn and does not have to be shuttled out of mitochondria
48
what AA's can be glucogenic?
Which are primarily ketogenic?
- ALL AA's can be glucogenic acoording to Dr. Bazaar
| - 2 are primarily ketogenic (leucine and lysine) but all can enter gluconeogenesis
49
Can FA be used to make glucose?
Why?
```
In mammals: no net conversion of
fatty acids to glucose
-catabolism of FA yields only
acetyl-CoA; mammals can’t use this
as precursor of glucose because
pyruvate dehydrogenase rxn is
irreversible; cells have no way to
convert acetyl-CoA to pyruvate
```
50
What organisms can use FA's to make glucose?
How do they do this and what pathways do they use for this?
plants, yeast, bacteria:
glyoxylate pathways allows
conversion of acetyl-CoA to OAA;
can use FA for gluconeogenesis
51
which intermediates of TCA can undergo oxidation to make OAA
All TCA intermediates can undergo oxidation to OAA
52
how can proteins be used to make glucose?
Some or all of C atoms of most amino acids derived from proteins
are ultimately catabolized to pyruvate or to TCA intermediates;
can undergo net conversion to glucose (glucogenic)
53
give an example of how alanine and glutatime are converted to be used in gluconeogenesis
[i.e. ala and
glutamine: after removal of their amino grps in liver mitochondria,
C-skeletons remaining (pyruvate and a-ketoglutarate are funneled
into gluconeogenesis]
54
compare glucokinase and hexokinase
Glucokinase (liver) vs hexokinase (muscle): much lower Km for
hexokinase; when blood glucose rises above 5 mM, glucokinase
activity increases, but hexokinase already near Vmax cannot
respond to increase in glucose.
55
what happens to the activity of glucokinase when blood glucose is high (after a meal)?
When blood glucose is high (after meal), excess glucose is
| transported to liver, where glucokinase converts it to G6-P
56
How is glucokinase regulated in the cell?
what transporter does glucose use to enter the the this type of cell?
Regulation of glucokinase by sequestration in nucleus: protein inhibitor of glucokinase draws it into nucleus when F6-P conc in liver is high and releases to cytosol when glucose conc is high
- glucose enter liver through GLUT2 transporters
57
what are the possible fates of pyruvate ? both directions
Pyruvate can be converted to glucose and glycogen via
| gluconeogeneis or oxidized to acetyl-CoA for energy production
58
Acetyl CoA allosterically regulates what enzymes?
Acetyl CoA produced by fatty acid oxidation or pyruvate
dehydrogenase complex activates pyruvate carboxylase and
inhibits pyruvate dehydrogenase (by stimulation of protein
kinase that inactivates the dehydrogenase)
59
What regulates of FBPase-1
inhibition by AMP and F26BP (no activation noted)
60
what regulates PFK-1 (glycolysis review)
- Inhibition by ATP, Citrate
| - Activated by ADP, AMP, F26BP
61
what determines F26BP levels
F26BP levels are determined
by rates of synthesis by PFK2
and breakdown by FBPase2
62
describe the structure and functions of PFK2 and FBPase2
what hormones regulate them?
PFK2 and FBPase2 - single bifunctional protein
- PFK2 uses ATP to phosphorylate F-6-P to F-2,6-Bisphosphate
- FBPAse2 dephosphorylates F-2,6-Bisphosphate to F-6-P releasing an inorganic Pi
- regulated in a reciprocal fashion by insulin and glucagon
63
What effect does glucagon have on PFK2 and FBPase2?
go through glucagon cascade to its effect of the pathways affected
what happens to blood glucose?
-Glucagon-stimulates adenylyl
cyclase,
-increased cAMP from
ATP,activates prot. kinase,
-phosphorylates PFK2/FBPase2,
-activates FBPase and inhibits
PFK2, lowering F26BP,
-inhibits glycolysis and stimulates
gluconeogenesis;
liver replenishes blood glucose in
reponse to glucagon
64
What effect does insulin have on PFK2 and FBPase2?
go through general cascade that you know.
list what is used and what is released.
- Its activates phosphoprotein phosphatase
- This enzyme dephosphorylates PFK2/FBPase2
- This inactivates FBPase2
- Activates PFK-2
- (H2O used, Pi released)
This stimulates production of F26BP
- This in turn stimulates glycolysis
- Inhibits gluconeogenesis
-
65
what stimulates glycogenolysis in myocytes? what about hepatocytes?
epinephrine in muscle cells and glucagon in liver cells
66
Describe cascades by glucagon and epinephrine what steps are different?
include how many of each molecule is made in each step: starting with step 2
Long summary based on Diagram
What are the final products in muscles vs the liver?
1) Epinephrine and glucagon bind to their own G-linked receptors which activate adenylyl cyclase through their GTP binding protein "G-s-alpha"
2) Active "G-s-alpha" triggers activates adenylyl cyclase which converts ATP to cAMP (x20 molecules)
3) Inactive PKA gets activated to become active PKA by cAMP (x10 molecules)
4) PKA phosphorylates inactive phosphorylase b kinase to make active phosphorylase b Kinase (100x molecules)
5) active phosphorylase b Kinase phosphorylates inactive glycogen phosphorylase b to active phosphorylase a (1000x molecules)
6) active phosphorylase a phosphorylates glycogen and produces G-1-P (10,000 molecules)
- The G-6-P produced in muscle enters glycolysis and helps with muscle contraction
- Liver cells convert G-1-P to glucose through a few rxns and eventually glucose out of hepatocyte to counter low glucose levels (10,000 molecules)
67
What are the regulator molecules of glycogenolysis?
-Activators: [AMP] and Ca2+ (only in the muscle cells!)
68
How many ATP's are used in phosphorylation of glycogen phosphorylase b to glycogen phosphorylase a?
which sidechain is phosphorylated?
2 ATP's one on each serine side chain
69
What enzyme dephosphorylates glycogen phosphorylase a?
what hormone activates this enzyme
Phosphorylase a Phosphatase (PP1)
activated by insulin
70
what happens that activates glycogen phosphorylase?
2 things on list from slide.
1) Activation of phosphorylase by covalent modification of specific amino acid
residues (phosphorylation) catalyzed by a specific kinase (phosphorylase
kinase) in a rxn that utilizes ATP.
2) Protein kinase A: activates phosphorylase kinase; occurs in 2 forms,inactive
and active; conversion to active form involves dissociation of regulatory
subunit from catalytic subunit (both dimeric R2C2) brought about by binding of
cAMP to R subunit (which causes a conformation change and separation from C)
71
how is Glycogen synthase regulated?
what role does insulin play?
- Glycogen synthase is also regulated by phosphorylation (via glycogen
synthase kinase 3, GSK3), which inactivates the synthase
-Insulin binding to its receptor triggers activation of glycogen
synthase by blocking GSK3 (via a phosphorylation cascade) and
activating a phosphatase PP1, which promotes dephosphorylation
and activation of glycogen synthase
72
low yield:
describe diagram from insulin cascade and its regulation of Glycogen synthase
1) insulin receptor phosphorylates IRS-1
2) Phosphorylated IRS-1 activates PI-3K
3) PI-3K convertsPIP2 to PIP3
4) this activates PDK-1 which in turn activates PKB
5) PKB phosphorylates GSK3, inactivating it.
- GSK3 activity no longer present, so Glycogen synthase is not deactivated.through phosphorylation.
- Phosphorylase a Phosphatase (PP1) is activated by insulin and it can dephosphorylate inactive Glycogen synthase b.
73
what are the regulatory molecules of Phosphorylase a Phosphatase (PP1)?
inhibitors: Glucagon, Epi
Activators: Insulin, GLucose-6-Phosphate, Glucose
74
What does CKII do?
After being primed by casein kinase 2 (CK2), glycogen synthase gets phosphorylated at a cluster of three C-terminal serine residues, reducing its activity. (uses the energy of ATP)
75
After eating what happens in the cell regarding GLycogen synthesis/breakdown and glycolysis?
include GSK3 and PP1 in your response among other enzymes. end wi
what transporter does glucose use to enter hepatocytes?
-After eating, elevation of blood
glucose triggers insulin release,
-That inactivates GSK3 and activates PP1,
-That activates glycogen synthase and
inactivates phosphorylase kinase, which stops glycogen breakdown;
-glucose enters hepatocytes via GLUT2,
-activation of glucokinase which phosphorylates
glucose and stimulates glycolysis and stimulates glycogen synthesis
*see mindmap on slide*
76
between meals what happens in the cell regarding GLycogen synthesis/breakdown and Glycolysis
Between meals, during fasting:
-drop in blood glucose triggers glucagon,
- that activates PKA,
- that activates glycogen phosphorylase,
- that phosphorylates and inactivates glycogen synthase,
- That blocks glycogen synthesis,
- PKA also activates gluconeogenic FBPase2,
- liver to produces G6P by glycogen breakdown and gluconeogenesis. It also stops using glucose to fuel glycolysis or make glycogen, which maximizes amount of glucose released into blood
* See mindmap on slide*
77
How are AA's used in as precursors for gluconeogenesis?
-C skeletons of glucogenic amino acids can be precursors for gluconeogenesis
-when glycogen is depleted, the liver uses the store of amino acids from
proteins, mostly from muscle, to synthesize glucose
-dietary protein: hydrolyzed by pepsin, trypsin, chymotrypsin, peptidases
-with most amino acids, the first step is deamination to yield the respective
α-keto acids, which are then converted to OAA
*see diapgran*
78
What AA's are ketogenic?
Which AA become acetyl CoA and which become acetoacetyl-CoA directly (per lehninger diagram)?
- Leucine, Lysine, Phenylalanine, Tryptophan and tyrosine: These are converted to Acetoacetyl-CoA or make ketone bodies
- Isoleuceine, leucine, Threonine and tryptophan form Acetyl CoA- This goes to form ketone bodies or enters the TCA cycle through the first step
79
What Amino Acids enter TCA by being converted to pyruvate first?
Alanine, Cysteine, glycine, Serine, Threonine, tryptophan
80
What AA's enter TCA by forming directly into OAA
Asparagine and Aspartate
81
What AA;s enter TCA into fumarate
Phenylalanine tyrosine
82
What AA;s enter TCA into Succinyl CoA
isoleucine, Methionine, Threonine, Valine
83
What AA;s enter TCA into at Alpha ketogluterate directly
Glutamate
84
What AA;s enter TCA into as Alpha ketogluterate but originate drom AA's that are first converted to malate
Arginine, Glutamine, histidine, Proline
85
What are amino acid precursors made from?
protein (dietary or from intracellular protein))
86
What are AA's broken down to?
NH4+ and carbon skeletons
87
What is NH4+ used for?
- Biosynthesis of AA's, nucleotides and biological amines
| - 2nd use is to form carbomoyl phosphate which enters the urea cycle and produces urea
88
Happens to carbon skeletons made from AA's
- Carbon skeletons are coverted to alpha-keto acids
| - these enter TCA cycle
89
What happens to alpha-keto acids derived from AA's when they enter The Citric Acid cycle
They produce:
-CO2, H2O, and ATP
- Also Oxaloacetate
- These can be used in gluconeogenesis
90
What connects the Urea cycle and TCA cycle
Aspartate-arginino-succinate shunt of TCA
91
what is dietary protein hydrolyzed by?
-dietary protein: hydrolyzed by pepsin, trypsin, chymotrypsin, peptidases
92
What does the liver use to make glucose when Glycogen stores are depleted?
-when glycogen is depleted, the liver uses the store of amino acids from
proteins, mostly from muscle, to synthesize glucose
93
How are most AA's processed before they can enter gluconeogenesis?
-with most amino acids, the first step is deamination to yield the respective
α-keto acids, which are then converted to OAA
94
what serves as a non-toxic carrier of N in the blood from the muscle to the liver?
what is the end result of the N (For the most part)?
1) in muscle: alanine serves as a nontoxic carrier of N in blood to liver where
N is prepared for excretion by synthesis of urea (via urea cycle)
95
What cofactor is used in aminotranferase and decarboxilation rxns
What is it a derivative of?
pyridoxal-5’-phosphate (a derivative
| of vitamin B6) AKA PLP
96
What do amino tranferases do?
What cofactor is required?
What is the cofactor a derivative of?
- aminotransferases: transfer the amino grp of amino acids to a-keto acids to
form new amino acids; require coenzyme pyridoxal-5’-phosphate (a derivative
of vitamin B6)
97
How does alanine transport N from the muscles to the liver?
-N from amino acids are gathered in form of glutamate
(acceptor is α-ketoglutarate)
-amino grp of glutamate is then transferred to
pyruvate to yield alanine
- once alanine is delivered to liver, amino grp of ala is
transferred back to α-ketoglutarate to yield glutamate
98
what is one fate of glutamate in the liver mitochondria?
what does that product lead to?
-in mitochondria, glutamate is subjected to oxidative deamination to yield
α-ketoglutarate and ammonium, which is used to synthesize urea (urea cycle)
99
what is the other major non-toxic carrier of N in the blood?
what is this molecule converted from and where does this carrier get its amino group from?
- glutamine: other major non-toxic carrier of N in blood; excess ammonia in
tissues is added to glutamate to form glutamine
100
- how do generic AA's give their amino groups to glutamate? list the reaction.
- list enzymes and cofactors
-alpha-ketogluterate reacts with an L-amino acid to form L-glutamate and an alpha-keto acid respectively
Enzyme: amino-tranferase
cofactor: PLP
101
Where does glutamine from the Extrahepatic tissues lose it's amino group?
what does it become?
- It loses its amino group in the mitochondria and it becomes glutamate
- enzyme: glutaminase
- The amino group enters the urea cycle
102
Where in the cell does alanine lose it's amino group?
what does it react with?
what does it it produce?
It loses its amino group in the cytosol by reacting with Alpha ketoglutarate and forming glutamate and an alpha ketoacid, respectively
103
Where in the cell does glutamate lose it's amino group?
What happens to that amino group (broadly)?
What enzyme catalyzes reaction?
- Glutamate loses it's amino group in the mitochondria
- that amino group enters the urea cycle in the form of ammonia
Enzyme: glutamate dehydrogenase
104
What is another possible fate for glutamate in the mitochondria (Besides losing its amino group)?
What is the enzyme in this reaction?
Glutamate reacts with oxaloacetate to make alpha ketoglutarate and aspartate, respectively.
The enzyme for this reaction is aspartate aminotransferase
105
What happens to aspartate generated from glutamate in the mitochondria?
It enters the urea cycle in step 2b
-It is incorporated to make the molecule Argininosuccinate
106
What happens to the ammonia group released by glutamate in the mitochondria?
What enzyme is involved in this reaction and what is the product?
Ammonium is reacted with bicarb to make carbamoyl phosphate
Consumes 2 ATP
enzyme: carbamoyl phosphate synthetase
107
What is the first reaction of the urea cycle?
Carbamoyl phosphate reacts with ornithine to make citrulline
Enzyme: Ornithine trans carboxylmoylase
Releases: Pi
108
What happens to citruline after it is formed?
What is the intermediate that is formed?
– It exits the mitochondria
-It is reacted with ATP and aspartame to make Argininosuccinate.
Enzyme: Argininosuccinate synthetase
- There is a Citrullyl- AMP intermediate
- (Production of this consumes one ATP)
- Aspartame is incorporated in the second half of the reaction. AMP is released
109
What happens to Argininosuccinate?
It reacts to form fumarate and arginine
Enzyme: Argininosuccinate lyase
110
What happens to fumarate and arginine that are formed in the urea cycle?
-Fumarate leaves the urea cycle.
– Arginine is reacted with H2O to form Urea and ornithine
-Enzyme: arginase 1
Note: ornithine is used to restart the cycle
111
How is PLP bound to its enzyme?
It is bound through noncovalent interactions and a schiff base linkage to a lysine residue at the active site
112
What enzyme converts glutamate to glutamine?
And how many steps?
Glutamine synthase
2 steps
– ATP is hydrolyzed in the first step
– Ammonium is incorporated into second step and a phosphate group is released
113
What enzyme converts glutamine to glutamate and deliver mitochondria?
What is released
Glutaminase
– H2O is consumed and NH 4+ is released
114
Describe the alanine cycle
Glucose in the muscle cells undergo glycolysis to form pyruvate.
– Pyruvate is reacted with glutamate (from muscle protein) to form alanine and Alpha ketoglutarate respectively
Enzyme: alanine aminotransferase
– Alanine is transported through the blood to deliver where it reacts with Alpha ketoglutarate to make pyruvate and glutamate respectively
Enzyme: alanine aminotransferase
-Pyruvate is then converted to glucose through gluconeogenesis
The cycle continues…
115
What are sugar nucleotides used for?
-Sugar nucleotides - substrates for polymerization of monosaccharides
into disaccharides, glycogen, starch, cellulose
116
What 2 enzymes does phosphorylase a phosphatase (pp1). dephosphorylate?
- glycogen phosphorylase a to glycogen phosphorylase b (the inactive form
- glycogen synthase b to glycogen synthase a ( the active form)
117
What phosphorylates and what dephoaphopherulase PFK2/F1.6BPase ?
cAMP dependent protein kinase phosphorylates it
Phosphoprotein phosphatase dephosphorylates it.
118
What affect does AMP have on glycogen and glucose levels?
How?
AMP by activating pfk1 and glycogen phosphorylase
Also inhibits FBPase 1
119
Liver phosphorylase a is inhibited by what?
How is this done?
Glucose:
- 2 Glucose bind and expose the phosphate on serines.
- PP1 dephosphorylates and reduces its activity
120
What does PKA phosphorylate?
What does each do?
Phosphorylate kinase
Pfk2 etc. complex
Pyruvate kinase
Glycogen synthase?
121
What does insulin activate?
What does each do?
Insulin sensitive protein kinase
PKB
Synthesis of hexokinase II, PFK1 and pyruvate kinase
