Week 13: Glycogen Synthesis, Pentose Phosphate Pathway, Fatty Acid and Lipid Metabolism Flashcards
Why is it essential that the regulatory mechanisms that activate glycogen synthesis also deactivate glycogen phosphorylase?
Because these two processes occur in the _______ in the cell, this regulation makes the ______ more efficient.
Such a regulatory mechanism prevents the simultaneous ______ of glucose monomers, preventing unnecessary reactions.
same location, net process
addition and removal
The free energy of formation of UDP-glucose from UTP and glucose-1-phosphate is close to zero. The pyrophosphate that is produced in this reaction, when hydrolyzed to two phosphate ions, ______ considerable energy. The coupling of these two reactions makes the net reaction ______.
The addition of glucose to glycogen as UDP-glucose is converted to UDP is approximately energy-neutral. Thus, the overall formation of glycogen is exergonic. The net effect is that some of the energy stored in the terminal phosphodiester bond of UTP and some of the energy stored in the phosphoester bond of glucose-1-phosphate is stored in glucose-glucose bonds in glycogen and some is lost in the hydrolysis of pyrophosphate.
releases, exergonic
Increasing the level of ATP favors both ____ and ______.
Decreasing the level of fructose-1,6-bisphosphate tends to stimulate ______ rather than _______.
The level of fructose-6-phosphate does not have a marked regulatory effect on _______.
gluconeogenesis and glycogen synthesis
glycolysis, gluconeogenesis or glycogen synthesis
gluconeogenesis or glycogen synthesis
Why is a different reducing agent (NADPH) is used in anabolic reactions rather than NADH, which is used in catabolic reactions?
This separation helps to untangle the two pathways so that the reactions are ______.
independently controllable
Anabolic and catabolic reactions must be regulated independently. Having two different redox species for the two pathways makes it much easier to regulate each pathway’s reactions without interfering with the other pathway’s reactions.
What are reasons that a fatty acid is linked to coenzyme A for metabolic purposes?
Acyl-CoAs are _______ compounds. An acyl-CoA has sufficient ______ to initiate the _______ process. The CoA is also a tag indicating that the molecule is destined for oxidation.
high-energy, energy
β-oxidation
molecular tag
Calculate the ATP yield for the complete oxidation of the 20-carbon saturated fatty acid arachidic acid.
(You should consider the β-oxidation steps, processing of acetyl-CoA through the citric acid cycle, and electron transport. Production of one GTP should be considered the equivalent of production of one ATP. Enter your answer to three significant figures.)
___ ATPs are gained for each arachidic acid oxidized
134
The 20-carbon arachidic acid will go through 9 rounds of β-oxidation. This will produce 9 FADH2s, 9 NADHs, and 10 acetyl-CoAs. These 10 acetyl-CoAs will each produce one FADH2, one GTP, and three NADHs in the citric acid cycle for a total of 10 FADH2s, 30 NADHs, and 10 GTPs from this cycle. There are thus a total of 39 NADHs and 19 FADH2s produced per arachidic acid.
Oxidation of one FADH2 via electron transport produces 1.5 ATPs while oxidation of one NADH via electron transport produces 2.5 ATPs. Thus, oxidation of the NADH produced in the metabolism of arachidic acid is responsible for the synthesis of 2.5 × 39 = 97.5 ATPs and oxidation of FADH2 is responsible for 1.5 × 19 = 28.5 ATPs.
The net production of ATP plus GTP is thus 10 + 97.5 + 28.5 = 136 per arachidic acid. A two ATP-equivalent is consumed in the initial activation step, so the overall net ATP gain is 134 ATPs per arachidic acid that is fully oxidized.
Calculate the ATP yield for the complete oxidation of a 21-carbon saturated fatty acid.
(You should consider the β-oxidation steps, processing of acetyl-CoA through the citric acid cycle, and electron transport. Production of one GTP should be considered the equivalent of production of one ATP. Enter your answer to three significant figures.)
_____ ATPs are gained for each 21-carbon fatty acid oxidized
129
The 21-carbon fatty acid will go through 9 rounds of β-oxidation. This will produce 9 FADH2s, 9 NADHs, 9 acetyl-CoAs, and one proprionyl-CoA. The 9 acetyl-CoAs will each produce one FADH2, one GTP, and three NADHs in the citric acid cycle for a total of 9 FADH2s, 27 NADHs, and 9 GTPs from this cycle. The proprionyl-CoA will produce one NADH and one FADH2 via the citric acid cycle along with one GTP. There are thus a total of 37 NADHs and 19 FADH2s produced per 21-carbon fatty acid.
Oxidation of one FADH2 via electron transport produces 1.5 ATPs while oxidation of one NADH via electron transport produces 2.5 ATPs. Thus, oxidation of the NADH produced in the metabolism of the 21-carbon fatty acid is responsible for the synthesis of 2.5 × 37 = 92.5 ATPs and oxidation of FADH2 is responsible for 1.5 × 19 = 28.5 ATPs.
The net production of ATP plus GTP is thus 9 + 1 + 92.5 + 28.5 = 131 per fatty acid. A two ATP-equivalent is consumed in the initial activation step for the original fatty acid and one ATP-equivalent is used in the conversion of proprionyl-CoA to succinyl-CoA, so the overall net ATP gain is 128 ATPs per 21-carbon fatty acid that is fully oxidized.
Calculate the ATP yield for the complete oxidation of the 20-carbon unsaturated fatty acid gadoleic acid (a 20:1-Δ9 fatty acid).
(You should consider the β-oxidation steps, processing of acetyl-CoA through the citric acid cycle, and electron transport. Production of one GTP should be considered the equivalent of production of one ATP. Enter your answer to three significant figures.)
_____ ATPs are gained for each gadoleic acid oxidized
133
The 20-carbon gadoleic acid will go through 9 rounds of β-oxidation. This will produce 8 FADH2s, 9 NADHs, and 10 acetyl-CoAs. (If the fatty acid had been saturated, 9 FADH2s would have been produced in the β-oxidation cycles. One less is produced here because one of the oxidation steps catalyzed by acyl-CoA dehydrogenase is not needed due to the presence of the C=C double bond in the original fatty acid.)
The 10 acetyl-CoAs from above will each produce one FADH2, one GTP, and three NADHs in the citric acid cycle for a total of 10 FADH2s, 30 NADHs, and 10 GTPs from this cycle. There are thus a total of 39 NADHs and 18 FADH2s produced per gadoleic acid.
Oxidation of one FADH2 via electron transport produces 1.5 ATPs, while oxidation of one NADH via electron transport produces 2.5 ATPs. Thus, oxidation of the NADH produced in the metabolism of gadoleic acid is responsible for the synthesis of 2.5 × 39 = 97.5 ATPs and oxidation of FADH2 is responsible for 1.5 × 18 = 27.0 ATPs.
The net production of ATP plus GTP is thus 10 + 97.5 + 27.0 = 135 per gadoleic acid. A two ATP-equivalent is consumed in the initial activation step, so the overall net ATP gain is 133 ATPs per gadoleic acid that is fully oxidized.
When oxaloacetate is in insufficient supply, as under starvation conditions, the ______ produced in β-oxidation cannot enter the ______ but rather is used to form ______.
acetyl-CoA
citric acid cycle
ketone bodies
Ketone bodies are produced when ______ lags behind _______.
Ketone bodies are produced when ______ is in insufficient supply.
carbohydrate metabolism
lipid metabolism
oxaloacetate
There are many differences in the pathways of fatty-acid breakdown and fatty-acid synthesis. Similarities include the use of ______ as a carrier, the use of ______ linkages, and a _____ unit that is fundamental to both pathways.
coenzyme A
thioester
two-carbon
The source of the glycerol in triacylglycerol synthesis is from _______ derived from _______
glycerol-3-phosphate
glycolysis
Glycerol comes from the degradation of acylglycerols or from the glycerol-3-phosphate derived from the glycolysis pathway.
_____ and _______ have cholesterol as a synthetic precursor.
Bile acids, steroid hormones (estradiol)
Why must cholesterol be packaged for transport rather than occurring freely in the bloodstream?
Cholesterol is _____ and will not readily _____ in the aqueous bloodstream.
______, which effective solubilize cholesterol, are needed to transport cholesterol in the blood.
nonpolar, dissolve
Carrier proteins
The pentose phosphate pathway can make both NADPH and pentose phosphates in roughly equimolar amounts by using only ______ reactions.
The pentose phosphate pathway can make mostly NADPH by using the _____reactions, the _______ reactions, and ______.
The pentose phosphate pathway can make mostly pentose phosphates by using _____ and the ______ reactions in reverse.
oxidative
oxidative, transaldolase and transketolase, gluconeogenesis
glycolysis, transaldolase and transketolase
UDP-glucose is used to ______ the glycogen chain
in synthesis.
extend
______ is the key regulatory enzyme in glycogen synthesis
* transfers a glucose moiety from ______ to the C-4 terminal residue of a glycogen chain to form an _______.
* requires an oligosaccharide of glucose residues as a primer.
- Glycogenin
- a small protein homodimer that synthesizes the ______.
- Each subunit of glycogenin generates an oligosaccharide of glucose residues ______ glucosyl units long.
- _______ then extends this primer.
Glycogen synthase
UDP-glucose, α-1,4-glycosidic bond
primer, 10–20
Glycogen synthase
Glycogen synthase adds to ______ ends, builds ______
non-reducing, straight chain
Branching enzyme in branching reaction cleaves _______ linkages off chains that are at least _____ long and clips of ______.
a-1,4 linkages, 11 units, 7-8 units
Glycogen synthase has:
- Phosphorylated ____ form (usually _____) and unphosphorylated _____ form (more _____)
- Note that phosphorylation has ______ effects on glycogen synthase than on glycogen phosphorylase
- T (_____ active) and R (_____ active) forms
b, inactive
a, active
Unphosphorylated form more active
opposite
less, more
Regulatory processes for glycogen synthase:
* Allosteric regulation: Binding of glucose 6-phosphate converts ____ form to ____ form. This conformational change favors ______ by protein phosphatase 1 (PP1).
- Covalent regulation:
- Insulin promotes ______ of glycogen synthase
- Glucagon and epinephrine promote ________.
T, R
dephosphorylation
Glucose-6-phosphate is a positive affector of glycogen synthase
desphosphorylation
phosphorylation
- Glycogen breakdown:
- ______ is the regulatory enzyme.
- Most active when ______.
- Glycogen synthesis:
*_______ is regulatory enzyme. - Most _____ when phosphorylated.
Phosphorylase, phosphorylated
Glycogen synthase
inactive
Phosphorylation of glycogen synthase by _____ to form glycogen synthase b _____ glycogen synthesis
protein kinase A
inhibits
Protein phosphatase 1 (PP1) shifts glycogen metabolism from the ______ mode to the ______ mode.
degradation
synthesis
Protein phosphatase 1 (PP1) _____ phosphoryl groups from phosphorylase kinase and phosphorylase a, inhibiting ________
removes
glycogen degradation
PP1 removes phosphoryl groups from glycogen synthase ____, converting it into the more active ____ form.
b, a
Insulin also helps in regulation of these pathways,
insulin inactivates _______ by ______ it
glycogen synthase kinase
phosphorylating
Glycogen synthase kinase is an enzyme that ______ a _____ to glycogen synthase
adds, phosphate
PPP Yields ______ and _____
- ______ is typically carrier for ______ pathways (______
movement of electrons generally use ______) - _____ are pre-cursors for ______
2. Glycolysis and PPP are ______ controlled.
NADPH, 5-C sugars
NADPH, biosynthetic (building/synthesizing)
Catabolic (breaking down), NADH
5-C sugars, nucleotides
coordinately (control tied together) because G-6-P has multiple pathways
The first phase of the pentose phosphate pathway is the ______ generation of ______. Has ____ enzymatic steps
The second phase is the _______ interconversion of a variety of sugars.
oxidative, NADPH, 3 enzymatic steps
nonoxidative
The first reaction of the pentose phosphate pathway, the ________ of ________ by _______, is the _______ step of the pathway.
The rate of the oxidative phase of the pentose phosphate pathway is controlled by the _______
_______ is the most important regulatory factor.
dehydrogenation
glucose 6-phosphate
glucose 6-phosphate dehydrogenase
rate-limiting
concentration of NADP+
[NADP+]
When ribose 5-phosphate needs exceed the needs for NADPH
_____ will occur to get to G-3-P and ______ phase of PPP will occur to get ribose-5-phosphate
Glycolysis, non-oxidative
When NADPH and ribose 5-phosphate needs are balanced:
the ______ phases of PPP occur and it stops after that
oxidative
(ex. when cells are rapidly dividing)
When more NADPH is needed than ribose-5-phosphate:
the _____ phase of PPP occurs, then the ribose-t-phosphate created is recycled back to make starting G-C-P through _____ phase
oxidative
non-oxidative
(ex. liver cells synthesizing fatty acids)
When both NADPH and ATP are required:
____ phase of PPP occurs and the ribose-5-phosphate created will undergo ______ phase to get metabolites to then make ATP through ______
oxidative
non-oxidative
glycolysis
_______ is the enzyme that controls the pentose phosphate pathway
Glucose-6-phosphate dehydrogenase
Fatty acid degradation, the activation and transfer of the ______ into the ______ and the _____ repetitive enzymatic steps of the _______ pathway.
acyl chain
mitochondria
four
beta oxidation
Chylomicron particles are 98% _______ with ______ and ______ on the surface
triacylglycerols
proteins, phospholipids
Triacylglycerols need to be packaged into chylomicron to enter the bloodstream as they are NOT water soluble
Triacylglycerols in adipose tissue are converted into ______. This happens in response to hormonal signals that result in a series of ______ that activate the _____.
free fatty acids
phosphorylations
lipases
Lipase adds ______ to break ester linkages stepwise until it makes three fatty acids and ______.
water, glycerol
Glycerol is soluble in _____, carried to liver and converted to ______, which can enter ______ or ______
blood
DHAP
glycolysis, gluconeogenesis
Fatty acids are then transported out of fat cell into ______ and carried on a protein called ______
blood plasma
albumin
The fatty acids incorporated into triacylglycerols in adipose tissue are made accessible in three stages.
1._______ to ______ fatty acids and glycerol into the blood for transport to energy-requiring tissues
- ______ of the fatty acids and transport into the ______ for ______
- _______ of the ______ to acetyl CoA for processing by the citric acid cycle
Degradation of TAG, release
Activation, mitochondria, oxidation
Degradation, fatty acids, acetyl CoA
Fatty acid activation by acyl CoA synthetase
______ and ______
Driven by hydrolysis of _________
spontaneous
irreversible
pyrophosphate
Activated Fatty Acid must be _____ into mitochondria
ported
Turned into acyl carnitine to go through mitochondria
Describe the repetitive steps of β oxidation
1) Oxidation (resulting in DB)
2) Hydration (Adding water, resulting in an -OH group)
3) Oxidation (C=O)
4) Thiolysis (adding CoA)