Exam 4 Flashcards
What are the functions of lipids?
Form a lipid bilayer of a cell-(glycerophospholipids, sphingolipids, cholesterol)
Source of energy- (triacylglycerol)
Signaling molecules- (arachidonic acid, released during stress or injury)
Hormones- (estrogen, testosterone, thyroxine, retinoate)
Vitamins- (A, D, E, K fat soluble/hydrophobic)
Define the characteristics of the lipid bilayer
Fluid- no clearly defined geometry; head groups move up/down, hydrocarbon tails wave
Asymmetric- different lipids are found in each “leaflet”
What are glycerophospholipids made of?
A phosphate head group, glycerol backbone,and 2 fatty acid chains derived from fatty acid. The R group on the phosphate group can vary.
R= Choline = Phosphatidylcholine
R= Ethanolamine = Phosphatidylethanolamine
R= Glycerol = Phospatidylglycerol
R= Serine = Phosphatidylserine
What are sphingolipids made of?
No glycerol backbone, a group derived from palmitate and another group from serine, the 2 fatty acid chains are derived from other fatty acids, the R group ion serine can vary.
R= Phosphatidylcholine = Sphinogomyelin
R= Monosaccharide = Cerebroside
R= Oligosaccharide = Ganglioside
What do fatty acids in water form?
Micelles
Describe what the melting point does to an acyl chain.
The melting point of an acyl chain decreases as the degree of unsaturation increases and the length of the acyl chain decreases.
Kinks in the chain lower the temperature.
Single bonds = unsaturation
How are triacylglyerols a stored form of energy?
The enzyme lipoprotein lipase ( activated by glucagon) converts triacylglycerol to glycerol (gluconeogenesis) + a fatty acyl groups. The fatty acyl groups are ATP.
What is Retinoate?
Lipid hormone
A metabolite of Vitamin A; required for growth and development; cell division and growth
What is the difference and function of Thyroxine (T4) and Triiodothyronine (T3)?
T4 has 4 iodine groups and T3 has only 3 iodine groups. Both are used for regulation of metabolism.
What is the lipid hormone cortisol and where is it derived from?
It is a stress hormone derived from cholesterol.
Where is testosterone derived from?
It is derived from cholesterol.
What enzyme does arachidonate use to convert to signaling molecules?
Cyclooxygenase
What are the two eicosenoids formed from the molecule aracidonate and the enzyme cyclooxygenase?
Prostaglandin H2 and Thromboxane.
Thromboxane is for platelet aggregation and vasoconstriction.
All act locally and not globally.
What is atherosclerosis?
Hardening of the arteries due to lipid accumulation in the blood vessel walls.
It is a slow progressive disease.
What do lipoproteins transport?
Cholesterol and other fats.
What are the different type of lipoproteins, from biggest to smallest?
Chylomicrons VLDL IDL LDL HDL
What is the function of chylomicrons?
To transport fats from intestines to tissues and cholesterol to liver.
What is the function of HDL?
High-density lipoproteins export cholesterol from the tissues to the liver.
“Good” cholesterol
HDL levels should be relatively high.
Degradation
What is the function of LDL?
Low-density lipoproteins carry cholesterol to the tissues.
“Bad” cholesterol
LDL levels should be relatively low.
What is the function of VLDL?
Very-low-density lipoproteins transport triacylglycerols from the liver to other tissues.
In cellular respiration, what happens to the fatty acids?
They are broken down into 2C and 3C intermediates that feed into the citric acid cycle.
What is another term for fatty acid degradation?
Beta-oxidation of fatty acids
What is the primary source of fatty acids?
Triacylglycerols
Fatty acids are ________ before they are ________.
Activated
Degraded
Describe the breakdown of fatty acid to acyl-CoA + AMP
Fatty acid + CoA + ATP -> Acyl-CoA + AMP + PPi
Activated fatty acids are acylated to CoA. The reaction is driven by ATP hydrolysis (2 ATP equivalents are used)
Long-chain-fatty-acid-CoA synthetase
Acyl-CoA has a thioester bond (similarly to Acetyl-CoA)
How are the acyl groups transferred?
Via the carnitine transporter.
Fatty acids after degradation are transported from the cytosol to the matrix via the carnitine transporter.
How many reactions does each round of beta-oxidation have?
Each round has 4 reactions.
Acyl-CoA is degraded into acetyl-CoA.
What is the first step of beta oxidation?
Starts with fatty acyl-CoA, hydrogens are removed and then enoyl-CoA is generated.
What is the second step of beta-oxidation?
Enoyl-CoA is catalyzed by enoyl-CoA hydratase to generate 3-Hydroxyacyl-CoA
What is the third step of beta-oxidation?
3-hydroxyacyl-CoA is oxidized by 3-hydroxyacyl-CoA dehydrogenase to ketoacyl-CoA. The hydrogens removed goes to the electron proton chain.
What is the final step of beta-oxidation?
Thiolysis; ketoacyl-CoA is catalyzed by thiolase and releases acetyl-CoA. The remaining acyl-CoA is 2 carbons shorter than the starting substrate. End product - fatty acyl-CoA + acetyl-CoA (this acetyl-CoA will enter the Kreb’s cycle). The acyl-CoA will undergo another round of the 4 reactions.
What are the beta-oxidation results in ATP production?
One round of beta-oxidation => 1 QH2 = 1.5 ATP
1 NADH = 2.5 ATP
1 Acetyl-CoA = 10 ATP
Citric acid cycle => 3 NADH = 7.5 ATP
1 QH2 = 1.5 ATP
1 GTP = 1 ATP
Total 14 ATP
How much ATP does a 16 carbon fatty acid chain make?
14 x 7 cycles = 98 ATP
98 ATP + 10 ATP (8th cycle) = 108 ATP
108 ATP - 2 used = 106 NET ATP
What does the oxidation of odd-chain fatty acids yield?
Propionyl-CoA
Oxidation of odd-chain fatty acids
Propionyl CoA -> Methylmalonyl CoA -> methylmalonyl mutase (requires cobalamine) -> Succinyl CoA
Succinyl CoA can go 1 of 2 routes- either to the TCA Cycle (anaplerotic) or the most common route is to Pyruvate -> Acetyl CoA -> TCA Cycle (substrate)
Where are most unsaturated fatty acids derived from?
From animals
Where are most saturated fatty acids derived from?
From plants
Which of the two fatty acid’s is greater than the other?
Unsaturated fatty acid yield less energy than saturated fatty acids. Unsaturated fatty acids use NADPH (2.5 ATP) and QH2 is by-passed (1.5 ATP). Unsaturated fatty acids form 4 less ATP.
Which two fatty acid oxidation’s occur in peroxisomes?
Very long chain fatty acids and branched fatty acids
Which enzyme catalyzes the first step of fatty acid synthesis?
Acetyl-CoA carboxylase
First, biotin is carboxylated.
biotin +HCO3- + ATP -> biotin-COO- + ADP + Pi
Second, the carboxyl group is transferred to acetyl-CoA by acetyl-CoA
carboxylase.
biotin-COO- + Acetyl-CoA -> Malonyl-CoA
Acetyl-CoA has 2 carbons
Malonyl-CoA has 3 carbonsWhere does fatty acid synthesis occur?
It occurs in the liver, specifically in the cytosol of the liver cells.
List the seven steps a fatty acid synthesis.
- Transfer of acetyl CoA to Cys
- Transfer of malonyl CoA to ACP (Acyl carrier protein)
- Condensation with decarboxylation
- Reduction of 3–keto group
- Dehydration
- Reduction of double bond
- Transfer from ACP to Cys
Steps 2-7 repeated six times to generate palmitate
________ and _______ catalyze elongation and desaturation reactions.
Elongases
Desaturases
How does fatty acid synthesis differ from fatty acid breakdown?
FAB occurs in the mitochondrial matrix (liver, muscle, heart) while FAS occurs in the cytosol (liver).
FAB’s cofactor is CoA and FAS’s cofactor is Acyl carrier protein ( ACP)
FAB’s oxidant is Q and NAD+ and FAS’s reductant is NADPH.
FAB energy input is 2 ATP equivalents consumed for activating fatty acid (regardless of # of C) and FAS energy input is 1 ATP consumed for every 2 carbons.
Fatty acid breakdown
Fatty acid -> Acetyl CoA
Fatty acid synthesis
Acetyl CoA -> MALONYL CoA -> Fatty Acid
Citrate transporter
Beta oxidation moves from the matrix to the cytosol via this transporter.
Carnitine transporter
Fatty acid synthesis moves from the cytosol to the matrix via this transporter.
How will insulin and glucagon affect the activity of acetyl CoA carboxylase?
Make lipids in times of eating and breakdown at times of fasting.
What inhibits acyl carnitine?
Malonyl CoA
What can inhibit Acetyl-CoA carboxylase?
Fatty acid
What can activate Acetyl-CoA carboxylase?
Citrate
What forms ketone bodies and what are ketone bodies?
Acetyl-CoA can form ketone bodies.
Ketone bodies are the water-soluble molecules containing the ketone group that are produced by the liver from fatty acids during periods of low food intake, carbohydrate restrictive diet, starvation, prolonged intense exercise, alcoholism or in untreated type one diabetes mellitus.
What are the 2 ketones?
Acetoacetate and 3-Hydroxybutyrate
3-Hydroxybutyrate is not really a ketone but is interchangeable
Ketone bodies are used as fuel by the what?
The brain and muscle
True/False
The rate of production of ketone bodies is much greater than their utilization.
True
What does triacylglycerol synthesis require?
A glycerol backbone and fatty acid activation.
Dihydroxyacetone phosphate -> glycerol-3-phosphate dehydrogenase (NADH + H+ —> NAD+) -> glycerol-3-phosphate
Describe the triacylglycerol and phospholipid synthesis
Glycerol-3-phosphate -> acyltransferase (twice) -> Phosphatidate -> phosphatase (lose Pi) -> Diacylglycerol (2 fatty acids attached to glycerol backbone) * phosphocholine enters -> Phosphatidylcholine
OR
* acyltransferase -> Triacylglycerol
How does cholesterol synthesis begin?
With Acetyl-CoA
What is the rate limiting step in cholesterol synthesis?
HMG-CoA reductase
Here cholesterol can be a feedback inhibition
What are some statin drugs categorized under?
HMG-CoA reductase inhibitor
What is the most important intermediate in cholesterol synthesis?
Mevalonate (6 carbons)
Eventually, it will be an Isopentenyl pyrophosphate (isoprenoid)
What is cholesterol derived from?
Squalene and squalene is derived from the isoprenoid precursor (an individual mevalonate).
Squalene -> Folded squalene -> Cholesterol (condensed; 4 rings)
What type of inhibition are statin drugs?
Competitive inhibition
What are the different ways cholesterol can be used?
It can make up a cell membrane, testosterone, cholate (colic acid; bile), and cholesteryl ester.
What is Familial Hypercholestrolemia?
A deficiency of functional LDL receptors
Cells can synthesize _________ as well as take it up from circulating ______.
Cholesterol
LDL (low-density lipoproteins)
It is done by the LDL receptor (uptake through endocytosis).
What do high-density lipoproteins remove from the cells?
Excess cholesterol
It transports the excess to the liver
What is the bacteria enzyme used in the Nitrogen Cycle?
Nitrogenase
How is ammonia assimilated?
By glutamate synthase and glutamine syntheTase.
Where does the reaction catalyzed by glutamate synthase occur?
In bacteria and plants
glutamate synthase converts a-Ketoglutarate + Glutamine to 2 Glutamate
Where does the reaction catalyzed by glutamine synthetase occur?
In bacteria, plants and animals.
“Mops up” free ammonium that is toxic to our body.
glutamine synthetase uses ATP to convert Glutamate to Glutamine
Glutamine and glutamate are _________ _________ molecules.
Nitrogen carrier
What does transaminase do?
Aka aminotransferase, moves amino groups between compounds. It catalyzes the transfer of an amino group to an a-keto acid.
Transaminase takes glutamate (amino acid) plus pyruvate (a-keto acid) and converts it to a-Ketoglutarate (a-keto acid) plus Alanine (amino acid)
What are the key pairs found in transaminase reactions?
Glutamate (amino acid) and a-Ketoglutarate (a-keto acid)
Transamination is freely ________
Reversible
What does transaminase require?
PLP (pyridoxal-5’-phosphate)
Where is PLP derived from?
From vitamin B6
What do we call a coenzyme that is covalently bound to an enzyme?
A prosthetic group
What amino acid is Enzyme-PLP Schiff base attached to?
It is attached to Lysine.
What are the 9 essential amino acids to be consumed?
Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine
Glutamate is a precursor for which 2 amino acids?
Proline and arginine
What is the major site of nitrogen metabolism?
Liver
What is serine a precursor for?
Cysteine and glycine
What is tetrahydrofolate?
THF is a carrier of one-carbon unit in amino acid and nucleotide biosynthesis.
THF can transfer a one-carbon unit like methyl, methylene, methenyl, formyl and formimino groups.
What does serine hydroxymethyl transferase do to serine?
It removes methylene and makes glycine.
How does the conversion of methionine to homocysteine occur?
Via S-adenosylmethionine (SAM)
SAM is a methyl group donor in many reactions.
What is a precursor for tyrosine?
Phenylalanine
phenylalanine hydroxylase converts phenylalanine to tyrosine by adding an OH group to the phenol ring.
What does the deficiency of phenylalanine hydroxylase cause?
PKU (phenylketonuria)
Tyrosine is a precursor to which signaling molecules?
Dopamine, norepinephrine, epinephrine, catechol
Tryptophan is a precursor to which signaling molecule?
Serotonin
Which 5 amino acids are both glucogenic and ketogenic?
Isoleucine -> Acetyl CoA + Succinyl CoA
Phenylalanine,Tryptophan, Tyrosine -> Acetoacetate + Ala/fumerate
Threonine -> Acetyl CoA + Gly
Name both ketogenic amino acids
Leucine, Lysine -> Acetyl CoA + Acetoacetate
What are the glucogenic precursors for amino acid catabolism?
Pyruvate, Oxaloacetate, a-Ketoglutarte, Succinyl CoA and Fumerate
What are the ketogenic precursors for amino acid catabolism?
Acetyl CoA and Acetoacetate
________ and ________ are converted to pyruvate.
Serine, Cysteine
Which are the glucogenic amino acids?
Asn -> Asp -> Oxaloacetate Gln -> Glu -> a-Ketoglutarate Arg, Pro, His -> Glu -> a-Ketoglutarate Met, Val -> Succinyl CoA Ser, Cys, Ala, Gly -> Pyruvate
How is 80% of excess nitrogen excreted?
As urea (urea cycle)
Where does urea synthesis occur?
In the liver; partly in the mitochondria and partly in the cytosol
Which 2 amino acids provide the nitrogen to the urea cycle?
Glutamate and aspartate
What supplies the carbon in the urea cycle?
Bicarbonate
What is the important regulatory step in the urea cycle?
Carbamoyl phosphate synthetase
In the glutamate dehydrogenase reaction, what does it use as a cofactor?
NAD+ or NADP+
Describe the Carbamoyl Phosphate Synthetase reaction
ATP activates the bicarbonate ion by transferring a phosphoryl group; ADP is released.
Ammonia attacks the carbonyl group on the carboxyphosphate, releasing an inorganic phosphate.
A second ATP phosphorylates carbamate to generate carbamoyl phosphate synthetase.
What activates carbamoyl phosphate synthetase?
N-Acetylglutamate
N-Acetylglutamate must be generated first
What does Purine nucleotide synthesis yield?
IMP , AMP, GMP (de novo purine synthesis)
What does PRPP stand for?
5-phosphoribosyl pyrophosphate
What happens first in the purine nucleotide synthesis?
PRPP is synthesized; ribose phosphate pyrophosphokinase converts ribose-5-phosphate to 5-phosphoribosyl pyrophosphate. Ribose-5-phosphate comes from the pentose phosphate pathway.
What is a purine made of?
Adenine and Guanine
How many steps is the purine ring constructed in?
10 steps
What do the 10 steps consist of?
- Nitrogens from Glutamine, Glycine and Aspartate
- Carbons from formyl-THF (tetrahydrofolate)
- Carbonyl from bicarbonate
Describe the first step of the purine nucleotide synthesis.
After PRPP is synthesized, the formation of 5-phosphoribosylamine, by the enzyme glutamine PRPP amidotransferase, is the committed step and is REGULATED.
The product is Inosine monophosphate (IMP)
What is synthesized in the last step of purine nucleotide synthesis from IMP?
AMP and GMP
AMP and GMP can generate each other
What is the difference between Ribose-5-phosphate AMP and Ribose-5-phosphate GMP?
R5p AMP has an amide group (NH2) on the top of the benzene ring and R5p GMP has an double bonded oxygen instead with an amide group on carbon 5.
Once AMP and GMP are formed, they can be phosphorylated by ATP to __________ and ___________ forms.
Diphosphate
Triphosphate
What activates Glutamine PRPP amidotransferase?
PRPP
What inhibits Glutamine PRPP amidotransferase?
IMP, GMP, and AMP
What does pyrimidine nucleotide synthesis yield?
UTP and CTP (de novo pyrimidine synthesis)
What is the pyrimidine base constructed from?
Glutamine, Aspartate and bicarbonate
What is the pyrimidine base attached to to form UMP?
PRPP
What is CTP synthesized from?
UTP (uridine triphosphate)
What is the difference between UTP and CTP?
UTP has a double bonded oxygen and CTP (cytidine triphosphate) has an NH2 group.
In RNA, nucleotides must be in ______ form for nucleic acid synthesis.
Triphosphate
In DNA, nucleotides must be in ______ form for nucleic acid synthesis.
Diphosphate
What is carbamoyl phosphate synthetase II?
An enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol.
It catalyzes the first step (committed step) of condensing glutamine, nitrogen and bicarbonate.
What activates CPS II (carbamoyl phosphate synthetase)?
ATP and PRPP
What inhibits CPS II?
UMP, UDP and UTP
What does ribonucleotide reductase convert ribonucleotides to?
Deoxyribonucleotides
What is nucleoside diphosphate converted to?
Deoxyribonucleoside diphosphate
True/False
In DNA, all nucleotides will be reduced at the 2’ position to get deoxyribose.
True
How are thymidine nucleotides produced?
By methylation
What is formed during the degradation of DNA and RNA?
Nucleotides, Nucleosides, Bases
What is the salvage pathway?
Purines and pyrimidine bases can be salvaged by phosphoribosyl transferases to form nucleoside monophosphates.
Give the 4 examples of nucleotide catabolism.
Purine base + PRPP Purine nucleoside-5’-monophosphate + PPi
Adenine +PRPP AMP + PPi
Pyrimidine base + PRPP Pyrimidine nucleoside-5’-monophosphate + PPi
Uracil + PRPP UMP + PPi
What happens to purine and pyrimidines that are not salvaged?
They undergo complete catabolism.
Give an example of complete nucleotide catabolism
Adenine
——> Uric acid (waste product) Urate
Guanine
Sodium Urate is poorly soluble in plasma; it can precipitate to cause gout.
