Exam 2 11/3 Howard Flashcards
Glycogenolysis
Glycogen breakdown
Glycogenesis
Glycogen synthesis
Glycogen metabolism is highly ___ and needs to respond to ____
regulated; hormones and metabolites
Where are glycogen reducing ends found
In a circle all around the glycogen molecule
If glycogenolysis is on, glycogenesis should be
Off (and vice versa)
Where is glycogen mainly found
Muscle and liver
Free anomeric carbon is
Reducing end
Why does the liver store glycogen
Needs to be able to maintain blood glucose between meals
Muscle stores glycogen for:
Its own energy needs
3 steps of glycogen breakdown
- release of G1P
- Remodeling of glycogen
- Formation of G6P
Fate of G6P
- fuel for ATP generation
- converted into glucose3
- PPP to generate NADPH or ribose
Glycogen degradation occurs at
Non-reducing end
Enzyme used to break down glycogen
Glycogen phosphorylase
Glycogen phosphorylase breaks down glycogen by ____ to form what molecule?
Phosphorylytic cleavage; G1P
In order to perform phosphorolytic cleavage of glycogen, it must use what phosporyl source?
Direct phosphoryl group donation (not from ATP!!)
Pyridoxal phosphate (PLP) is a derivative of
Pyridoxine (vitamin B6)
____ requires Pyridoxal phosphate (PLP)
Glycogen phosphorylase
Where does glycogen phosphorylase stop?
4 residues away from a branch point
Transferase
Shifts a block of three glycosyl residues
alpha 1,6 glucosidase
Hydrolyzes alpha 1,6 glycosidic bond (now is just a lone glucose molecule
In eukaryotes, _____ and ____ is a single bifunctional enzyme during glycogen debranching
transferase, alpha 1,6-glucosidase
Phosphoglucomutase converts ____ into ____
G1P to G6P
Glycogen phosphorylase is a ____ (structure)
dimer
Glycogen phosphorylase - allosteric _____
Energy state
Glycogen phosphorylase undergoes ______ in response to hormonal signals
reversible phosphorylation
Which phosphorylase state is phosphorylated and where?
Phosphorylase a; at a serine 14 reside in each subunit
What phosphorylates Glycogen phosphorylase
phosphorylase kinase
Phosphorylase a favors
R state
Phosphorylase b favors
T state (taut)
Glycogen phosphorylase has _____ specificity
Tissue
Phosphorylase b is found in
Muscle
In muscle, a low energy charge (represented by _____) favors the transition to _____
high conc of AMP; R state
What can increase epinephrine
fear or excitement of exercise
If epinephrine is increased (a ____ response), _____ phosphorylates to _____ form
hormonal; muscle phosphorylase; phosphorylase a
Phosphorylase a is found in
Liver
In liver phosphorylase, when glucose is already abundant, _____ is not mobilized because _____ shifts the equilibrium to the ___ state which inactivates the enzyme
glycogen; glucose; T
Glycogen synthesis is done by what enzyme
glycogen synthase
____ is reciprocally regulated
Glycogen synthesis
UDP glucose is
An activated form of glucose (activated glucose donor)
How is UDP glucose made (enzyme and starting substrate)
Enzyme - UDP-glucose pyrophosphorylase
Starts from G1P
Phosphoglucomutase converts G1P into
G6P
_____ catalyzes transfer of glucose from UDP-glucose
Glycogen synthase
Glycogen has ____ reducing end(s) and ___ non-reducing end(s)
1 reducing, 2 non-reducing
phosphorylase a is usually ___________
active
phosphorylase b is usually _________________
inactive
phosphorylase a favors the ____ state
R state (relaxed)
phosphorylase b favors the ____ state
T state (taut)
A low energy charge, represented by high concentrations of AMP, favors the transition to the ___ state (more active) of muscle phosphorylase
R state
Fear or the excitement of exercise increases epinephrine: phosphorylates to Phosphorylase ____ form: hormonal response (in muscles)
A form (active)
Branching increases the _____________ of glycogen; inc. rate of synthesis and degradation
Solubulity
Is glycogen synthase a phosphorylated? Is it active or inactive?
NOT phosphorylated, active
Is glycogen synthase b phosphorylated? Is it active or inactive?
phosphorylated, NOT active
Is phosphorylase a phosphorylated? Is it active or inactive?
phosphorylated, active
Is phosphorylase b phosphorylated? Is it active or inactive?
NOT phosphorylated, NOT active
The Pentose Phosphate Pathway is also called…..
- Phosphogluconate pathway
- Hexose monophosphate shunt
The Pentose Phosphate Pathway is a major source of ____________ for reductive biosynthesis
NADPH
What pathway provides Ribose for RNA, DNA, ATP, NADH, FAD, and CoEnzyme A synthesis?
Pentose Phosphate Pathway
The enzymes involved in the pentose phosphate pathway are ____________ enzymes
Cytoplasmic
Does the pentose phosphate pathway consume or produce ATP?
NO
The oxidative phase of the pentose phosphate pathway generates what?
NADPH
The nonoxidative phase of the pentose phosphate pathway interconverts _______________
Phosphorylated sugars
True or False: the two phases of the pentose phosphate pathway can function together or independently depending on metabolic needs
True
What controls the rate of the pentose phosphate pathway?
Level of NADP+
Flow of __________________ depends on the Need for NADPH, ribose 5-phosphate, and ATP (pentose phosphate pathway)
G6P
If much more ribose 5-phosphate is needed than NADPH: ribose 5-phosphate is made ______________ NADPH synthesis (Mode 1 pentose phosphate)
Without
If need for NADPH and ribose 5-phosphate is equal, then _____________ are made (Mode 2 pentose phosphate)
Both
If much more ___________ is needed (Mode 3 pentose phosphate)
NADPH
IF both NADPH and _____ is needed (Mode 4 pentose phosphate)
ATP
What are sources of triglycerides?
- Diet
- Synthesis and storage
Where are triglycerides found in the cell?
Cytosol of adipose cells; muscle
What are efficient energy stores that are:
-Reduced
-Anhydrous
Triglycerides
triglycerides are broken into what by hormone sensitive lipases?
Glycerol and free fatty acids (and albumin)
What are the “fates” of triglyceride?
- glycerol goes to glycolysis/gluconeogenesis (in liver)
- fatty acids (ffa) go to fatty acid oxidation
Glycerol is absorbed into the liver and converted into what intermediate of glycolysis/gluconeogenesis?
glyceraldehyde 3-phosphate
What is the first stage of fatty acid oxidation?
ffa converted to fatty acyl CoA
What is the 2nd stage of fatty acid oxidation?
b-oxidation and Acetyl CoA production
What is the 3rd stage of fatty acid oxidation? (after TCA cycle)
Electron transport to generate a proton-motive force
What is the 4th stage of fatty acid oxidation? (after TCA cycle)
ATP synthesis
What is the 4th stage of fatty acid oxidation? (after TCA cycle)
ATP synthesis
Fatty acids use _____ to bind to CoA and form Acyl CoA
ATP (forms thioester linkage)
Where does the reaction between fatty acids and CoA occur?
Outer mitochondrial membrane
How do acyl groups enter mitochondria?
- Fatty acid conjugated to carnitine
- Translocase exchanges acyl carnitine for carnitine
- Re-form Acyl CoA in mito matrix
Where does beta oxidation occur?
mitochondria
beta oxidation of fatty acids is a repetition of sequence of ____ reactions
4
What happens in beta oxidation of fatty acids?
- Acetyl CoA enters TCA
- NADH and FADH2 carry electrons to oxidative phosphorylation
What is produced per round of beta oxidation?
- 1 FADH2
- 1 NADH
- 1 Acetyl CoA
- 1 Acyl CoA shortened by 2 Cs
What is required for fatty acid synthesis?
NADPH
What happens in fatty acid synthesis?
Sequential addition of 2 C from acetyl CoA
What is the enzyme used in fatty acid synthesis?
fatty acid synthase
__________ are not stored in the body or excreted, they are turned into fuel
proteins
What is the a-amino group converted to in protein metabolism?
urea
What is the Carbon skeleton converted to in protein metabolism?
metabolic intermediate (acetyl CoA, pyruvate, TCA intermediate)
What is the site of protein degredation?
Liver
What is the first step of protein degradation?
removal of nitrogen
(a-amino group transferred to a-ketoglutarate to form glutamate and ammonium ion)
What is the second step of protein degradation?
Carbon skeleton metabolized
Transamination and deamination of amino acids produces ____________________
ammonium ion
Urea cycle functions to
Eliminate excess nitrogen
Where does the urea cycle start
In mitochondria
The urea cycle occurs almost exclusively in the _______
Liver
urea formed in the liver passes via bloodstream to ___________ and is then excreted in urine
Kidneys
What is pyruvate converted into
Acetyl CoA
Where is pyruvate transported to
Mitochondria
Is the conversion of pyruvate to acetyl CoA reversible?
No, essentially irreversible
What does the conversion of pyruvate to acetyl CoA produce?
CO2 and NADH
What is the size of the pyruvate dehydrogenase complex?
4,000-10,000 kDa- Huge!!
What is the prosthetic group of pyruvate dehydrogenase complex?
thiamin pyrophosphate (TTP)
Active form of thiamin (B1)
Is the inactive form of pyruvate dehydrogenase phosphorylated or not?
Yes it is
What directly inhibits pyruvate dehydrogenase?
- NADH
- acetyl CoA
- ATP
What stimulates pyruvate dehydrogenase?
Pyruvate; ADP indirectly
Key irreversible step in the metabolism of glucose that uses pyruvate dehydrogenase
Pyruvate into acetyl CoA
Acetyl CoA is end product of:
- glycolysis via pyruvate
- fatty acid oxidation
- amino acid degradation
- TCA intermediates
The citric acid cycle, or Krebs cycle, Harvests electrons from what?
Carbon fuels (acetyl group)
The krebs cycle provides precursors to what?
- amino acids
- nucleotide bases
- oxaloacetate (to make glucose)
Where does the Krebs cycle take place?
Mitochondria
Oxaloacetate (C4) + acetyl unit (C2) = ?
tricarboxylic acid (C6)
the krebs cycle regenerates what?
Oxaloacetate
What is produced in the Krebs cycle?
carbon dioxide, NADH, FADH2
What is lost in the krebs cycle as CO2?
acetyl group
Does the Krebs cycle require oxygen?
No
What catalyzes the condensation of acetyl CoA and Oxaloacetate?
citrate synthase - pace setting enzyme
(irreversible reaction)
What enzymes are the key control points of the Kreb’s cycle?
- isocitrate dehydrogenase
- α-ketoglutarate dehydrogenase.
The concentration of ATP and NADH can regulate what cycle?
Kreb’s cycle
High citrate concentration inhibits what?
Citrate synthase
Isocitrate dehydrogenase is inhibited by what?
NADH, ATP
Isocitrate dehydrogenase is stimulated by what?
ADP
a-ketoglutarate dehydrogenase
is inhibited by what?
succinyl coenzyme A (competes for CoA)
The electron transport chain is a series of electron carriers where?
Inner mitochondrial membrane
In the ETC, electrons are passed from NADH and FADH2 to O2 to form ______________
Water
In the ETC, electrons are passed from NADH and FADH2 to O2 to form ______________
Large decrease
free energy is captured in what form in the electron transport chain?
hydrogen ion (proton) gradient and voltage gradient across inner membrane
proton-motive force drives _______ synthesis
ATP
Where are uncoupling proteins found?
Inner mitochondrial membrane
What do uncoupling proteins do?
- reduce ATP synthesis
- dissipate proton motor force
What is well developed in brown adipose tissue in small mammals and in newborns?
uncoupling proteins
What increases due to uncoupling proteins?
- glucose oxidation
- heat production
(ATP levels no longer inhibiting)
What activates uncoupling proteins?
thyroid hormones