Exam 2 Flashcards
Glycogen is the readily metabolized storage form of _______
glucose
Branched homopolymer of glucose linkages are alpha (1-) and alpha (1-) branched
4
6
Glucose can be added and removed from the ___________ ends of glycogen
non-reducing (free 4’-OH)
In the liver the synthesis and breakdown of glycogen is regulated to maintain blood ________ levels
glucose
In the muscle the synthesis and breakdown of glycogen is regulated to meet the _____ requirements
energy (when blood glucose levels fall, glycogen will be broken down to release glucose units)
What are the three enzymes in glycogenolysis
glycogen phosphorylase
phosphoglucomutase
glycogen debranching enzyme
A phosphorylase enzyme uses ___ to attack
Pi
A phosphatase enzyme uses ____ to attack
H2O
Phosphorylase yields G1P which is _______ meaning it gets trapped in the cell
charged
What vitamin cofactor does glycogen phosphorylase use
Pyridoxal Phosphate (PLP)
Pyridoxine (Vitamin B6)
The hydrophobic ring of PLP helps keep ____ out of the active site
water (and Pi in)
PLP is also the required cofactor for the enzymes in ____ _____ metabolism
amino acid
Glycogen phosphorylase cleaves off residues without having to dissociate and rebind after each reaction
true
Glycogen phosphorylase releases ____ and needs ____ to enter glycolysis
G1P
G6P
Glycogen phosphorylase will stop ___ residues away form a branch point
4
Debranching enzyme shifts ___ glycosyl units from one strand to another
3
What organ regulates blood glucose levels
liver
Glycogen is principally stored in the cytosolic granules of which two organs
liver
muscle
How is glucose activated in order to be incorporated into glycogen
glucose attached to a nucleotide: UDP
The activated intermediate _________ serves the substrate for the glycogen synthesizing enzyme
UDP-glucose
What are the 4 reasons for attaching a nucleotides
-attachment is favorable
-sugar nucleotide has many R groups
-a nucleotide is an excellent leaving group
-attaching glucose to UDP creates separate collections of glucose in the cell after a glucose rich meal
What three enzymes catalyze the steps involved in glycogen synthesis
UDP-glucose pyrophosphorylase
Glycogen Synthase
Glycogen Branching Enzyme
Glycogen synthesis can only use the _____ linkages
1-4
Glycogen synthase can only add onto existing glycogen chains of at least ___ residues long
4
Insulin stimulates gluose uptake by the _____ receptor
Glut4
Glycogen branching enzyme transfers a segment of a _____ linked sugar and transfers them on a ____ linkage
1-4
1-6
The transferred segments in glycogen branching enzyme must be how many residues long
11
The activity of glycogen synthase and glycogen phosphorylase is controlled by what
phosphorylation
Glycogen phosphorylase is ______ when phosphorylated
active
Glycogen synthase is ________ when phosphorylated
inactive
Glucose binds directly to glycogen phosphorylase and shifts its ________ equilibrium from the active R to the inactive T state
allosteric
Glucagon and Epi stimulate what and inhibit what
stimulate: glycogen breakdown
inhibit: glycogen synthesis
Insulin stimulate what and inhibit what
stimulate: glycogen synthesis
inhibit: glycogen breakdown
Pyruvate can be a source of new glucose made by liver during what
gluconeogensis
Pyruvate can either be sent out to blood when glucose levels are _____ or stored in liver as ______ for later use
low
glycogen
Pyruvate can be a source of Acetyl-CoA which can be used to make _____ via CAC and ETC or converted to ____ for energy storage
ATP
fat
The PDH reaction is a link between glycolysis and ____
TCA
Oxidative decarboxylation of pyruvate is irreversible because the release of ____ is very favorable
CO2
For pyruvate dehydrogenase complex what are the three reactions
E1: pyruvate dehydrogenase
E2: Dihydrolipoyl Transacetylase
E3: Dihydrolipoyl Dehydrogenase
What are the 5 cofactors needed for pyruvate dehydrogenase complex
TPP
Lipoate
FAD
NAD+
CoA
What is the first step of PDH
pyruvate dehydrogenase
require TPP cofactor
Decarboxylation of pyruvate to an aldehyde
What is TPP (thiamine pyrophosphate) derived from
thiamine
vit B1
What is the second step of PDH
Dihydrolopoyl Transacetylase
Require Lipoate Cofactor
Oxidation of aldehyde to a carboxylic acid and form acetyl-coA
Lipoate cofactor derived from
Lipoic Acid
covalently linked to the enzyme via an amide bond between a NH2 of a lysine residue and the COOH of lipoic acid
What is the third step of PDH
Dihydrolipoyl Dehydrogenase
Requires FAD and NAD+
Catalyzes reoxidation of lipoamide cofactor and form NADH and regenerate oxidized FAD cofactor
Product inhibitors always bind in the ___________ of the enzymes
active site
What are the products of the PDH reaction
Acetyl-CoA and NADH
Feedback inhibitors are allosteric meaning they bind in ________ site on enzyme
separate
What are the feedback inhibitors of PDH
ATP and GTP (inhibit)
AMP (activate)
What does phosphorylation of E1 vs dephosphorylation of E1 do to PDH
phosphorylation: inactivates PDH (kinase)
dephosphorylation: activates PDH (phosphatase)
High ATP -> PDH kinase phosphorylates PDH -> less active PDH -> less ________ made
acetyl-coA
High AMP -> kinase is less active and PDH phosphatase removes phosphate from PDH -> more active PDH -> more _______ made
acetyl-coA
PDK kinase is inhibited by what
pyruvate
ADP
NAD+
CoA-SH
PDH phosphatase is activated by what
insulin (high blood glucose)
Is PDH enzymes are defective or turned off what builds up
lactic acid (its produced from excess pyruvate)
What is Rxn 1 of Citric Acid Cycle
-carbon to carbon bond formation by condensation of acetyl-CoA and oxaloacetate
-citrate synthase
What is Rxn 2 of Citric Acid Cycle
-Isomerization by dehydration/rehydration
-Aconitase
What is Rxn 3 of Citric Acid Cycle
-Oxidative decarboxylation
-Isocitrate dehydrogenase
What is Rxn 4 of Citric Acid Cycle
-oxidative decarboxylation
-alpha-ketoglutarate dehydrogenase complex
What is Rxn 5 of Citric Acid Cycle
-Substrate level phosphorylation
-succinyl-CoA synthetase
What is Rxn 6 of Citric Acid Cycle
-Redox reaction to generate FADH2
-succinate dehydrogenase
What is Rxn 7 of Citric Acid Cycle
-hydration across double bond
-fumarase
What is Rxn 8 of Citric Acid Cycle
-oxidation of alcohol to ketone
-malate dehydrogenase
the FAD cofactor that accepts the electrons in this reaction is _______ linked to the succinate dehydrogenase enzyme
covalently
Succinate dehydrogenase is NOT located in the ____________ _______
mitochondria matrix (its in the inner layer)
The TCA cycle generates how many ATP
1
What are the regulation steps of the TCA
citrate synthase (1)
isocitrate dehydrogenase (3)
alpha-ketoglutarate dehydrogenase (4)
What allosterically inhibits citrate synthase
ATP
NADH
succinyl CoA
What allosterically inhibits isocitrate dehydrogenase, what allosterically activates it, and what product inhibitions it
allosterically inhibit: ATP
allosterically activate: ADP
product inhibition: NADH
What are the allosteric regulators inhibitors, activators and product inhibitors of TCA
allosterically inhibitors: ATP, GTP
allosterically activators: AMP
product inhibitors: succinyl-CoA
Citrate is used to make
fatty acids/sterols
alpha-ketoglutarate is used to make
amino acids, purines, pyrimidines
succinyl CoA is used to make
porphyrin ring of heme
oxaloacetate is used to make
glucose, amino acids, purines, pyrimidines
What are the 4 biosynthetic intermediates of TCA
citrate
alpha-ketoglutarate
succinyl CoA
oxaloacetate
The act of replenishing TCA cycle intermediates that have been extracted for biosynthesis is called
anaplerasis
How to make oxaloacetate without using TCA cycle
pyruvate
Pyruvate carboxylase requires _____ as a cofactor
biotin
Pyruvate carboxylase is a critical enzyme that is necessary for the synthesis of oxaloacetate from _______ or be used to make new ______
pyruvate
glucose
How to counteract pyruvate carboxylase deficiency
vitamins
glucose-rich diet
not fasting or ketosis
What are the 4 major roles of fatty acids
building blocks of phospholipids
fuel
hormones
anchor proteins
Why are fatty acids such good fuels
they are highly regulated and are anhydrous
Fatty acids are stored in the body as _____________ esters
triacylglyceride
What are the two primary sources of TG
absorption from the diet not regulated
mobilization of stored fat in adipose tissue highly regulated
Dietary TG must be broken down into free _____ ______ before being absorbed
fatty acids
Most fat absorption occurs in the
duodenum
TG are incorporated into the micelles with their ester bonds pointing towards _____ of the micelle
surface
Pancreatic _____ cleave the ester bonds of the triacylglycerols while in the micelles
lipases
Pancreatic Lipase is the enzyme inhibited by ______
Xenical
Once inside the cell, the triacylglycerides are reformed and packaged into _______ which enter the lymph system
chylomicrons
true or false uptake of fatty acids is not regulated
true (fatty acids are in the intestines which can not be regulated)
What are the three stages of fatty acid processing
-triglycerols are degraded to free fatty acids and glycerol in the adipose tissue and transported to other tissues
-fatty acids are activated and transported into the mitochondria
-fatty acids are broken down into two-carbon acetyl-CoA units and fed into the TCA
Hormones trigger ______ in adipose tissue
lipolysis
When triacylglycerol lipase is phosphorylated it is _______
active
Breakdown of stored fat is controlled by a _______ cascade
hormone
When blood glucose levels are low or in fight or flight response ____ is broken down for energy needs
fat
Hydrophobic fatty acids bind to _______ in the blood
albumin
In order for free fatty acids to be oxidized for energy what needs to occur
the COO- group of the free fatty acid must be activated so they can be transported into the mitochondria for degradation
Carboxylate converted to thioester = higher energy = ________ group
activated
What enzyme cataylzes the conversion to make the COO- group of the free fatty acid activated
acyl-CoA synthetase
The long fatty acid gets attached to a carrier molecule called what
carnitine
When fatty acids is attached to carnitine the product is what
acyl-carnitine
What inhibits the attachment of carnitine to a fatty acid tail
malonyl-CoA
True or False: Fatty acid degradation will occur when fatty acid synthesis is occurring
false (the fatty acid will not get transported to the mitochondria where degradation takes place)
Defects in carnitine shuttle transport system result in what two things
hypoketosis
hypoglycemia
The process of FA degradation is called
beta oxidation
How many carbons are removed at a time in beta oxidation
2 carbons
What are the 4 processes of beta oxidation
oxidation
hydration
oxidation
thiolysis
Rxn 1 in beta oxidaiton
enzyme: acyl CoA dehydrogenase
electrons passed from FAD to hydride ion then to ETC
What are the differences between the 3 forms of acyl-coA dehydrogenases
differ in preference in long, medium, or short chain acyl-coA
Rxn 2 in beta oxidation
enzyme: enoyl CoA hydratase
h2o added across trans C=C
Rxn 3 in beta oxidation
enzyme: L-hydroxyacyl CoA dehydrogenase
oxidize L-isomer
needs NAD+ which accepts hydride to form NADH
oxidized to form 3-ketoacyl CoA
Rxn 4 in beta oxidation
enzyme: Beta ketothiolase
cleave thiol group of a new CoA to form acetyl-coA and acyl-coA
What is the end result of one beta oxidation rotation
1 FADH2
1 NADH
1 Acetyl-CoA
The oxidation of fatty acids can be a significant source of what
dietary water
In odd fatty acids chains what is produced
propionyl coA and acetyl coA
Propionyl CoA must be converted to TCA intermediate ______________
succinyl coA
If acetyl-coA can not be released during FA breakdown and enter the TCA cycle what happens
-there is not enough oxaloacetate around to turn the cycle
-acetyl coA will be converted to ketone bodies in the liver
________ is also a precursor for synthesis of other biomolecules including cholesterol
HMG-CoA
What are the 3 ketone bodies
acetoacetate (used for fuel)
beta-hydroxybutyrate (used for fuel)
acetone (exhaled)
Ketone bodies that are made as fuel are made in the liver then ________ in the blood to other tissues for use
transported
Ketone bodies are a _______ soluble equivalent of acetyl-coA units
water
How can ketone bodies be used by other tissues
acetoacetate is cleaved to produce 2 acetyl-coA units that can be fed into TCA for energy
High levels of acetoacetate ____________ fat breakdown
decreases
When liver beta-hydroxybutyrate is transported to muscle, brain, or other tissues it can be converted to what and can enter what cycle
Converted to acetyl-coA
enter TCA cycle
During starvation or diabetes, oxaloacetate is used to make glucose which can not be used in the TCA cycle what is the result of this occurrence
ketone body production
High concentrations of ketone bodies can be harmful and lead to what
ketoacidosis (acids decrease blood pH)
