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173 Cards in this Set

  • Front
  • Back

What is the most concentrated storage form of fuel?

Fats (mostly hydrocarbon)!

Fatty acids are broken down into what?

Acetyl CoA

Fatty acids are stored as what?

Triacylglycerols

Fatty acids are degraded and synthesized in what number units?

2-carbon units!

TRUE OR FALSE: The key intermediates between fatty acid degradation and synthesis are not the same.

FALSE. They are the same.

What is perilipin?

Protein that once phosphorylated by Protein Kinase A makes triacylglycerols more accessible to mobilization and triggers the release of the coactivator adipose triglyceride lipase.

Triacylglycerols in adipose tissues are converted into fatty acids in response to what?

Hormonal signals that activate the 7TM receptors that activate cAMP and Protein Kinase A.

In hormonal regulation of Lipase, protein kinase A activates triacylglycerol lipase which does what?

It releases a fatty acid from triacylglycerol converting it into diacylglycerol

Glycerol released from fat by lipase is sent to what?

Glycolysis pathway!

What completes the mobilization of fatty acids with the production of a free fatty acid and glycerol?

Monoacylglycerol lipase

What 2 things induce lipolysis?

1. Epinephrine


2. Glucagon

What is albumin?

Blood protein that serves as a carrier for insoluble fatty acids in the blood stream.

What are the 3 steps to convert glycerol into glyceraldehyde 3-phosphate? When is NADH produced?

1. Glycerol to L-Glycerol 3-phosphate


2. L-Glycerol 3-phosphate to Dihydroxyacetone phosphate (NADH IS PRODUCED)


3. Dihydroxyacetone phosphate to glyceraldehyde 3-phosphate

Once converted to glycerol, what two pathways can glycerol undergo?

1. Glycolysis to Pyruvate


2. Gluconeogenesis to Glucose

Where are fatty acids oxidized?

Mitochondrial matrix

In order to be oxidized, fatty acids must be activated by what?

CoA!

What are the 2 steps to fatty acid activation?

1. Fatty acid reacts with ATP to form acyl adenylate and pyrophosphate



2. Sulfhydryl group of CoA attacks the acyl adenylate to form acyl CoA and AMP

How do activated fatty acids cross the inner mitochondrial membrane?

They must be linked to the alcohol carnitine

What are the 4 basic reactions of fatty acid degradation (The Beta Oxidation Pathway)?

1. Oxidation to form alphabeta double bond (FADH2)


2. Hydration across the double bond


3. Oxidation (NADH)


4. Thiolysis by CoA to displace the first 2 carbons

What is the first step of fatty acid breakdown?

Acyl CoA is oxidized via FAD (forming FADH2) to form trans-delta-enoyl CoA

What is the second step of fatty acid breakdown?

Trans-delta-enoyl CoA is hydrated to form L-3-hydroxyacyl CoA

What is the third step of fatty acid breakdown?

L-3-hydroxyacyl CoA is oxidized via NAD+ (forming NADH) to form 3-ketoacyl CoA

What is the fourth step of fatty acid breakdown?

3-ketoacyl CoA is thiolysed by CoA to form Acyl CoA (which is shortened by 2 C) and Acetyl CoA

In each beta oxidation pathway reaction cycle, how many carbon atoms are released from the fatty acid? How many FADH2, NADH, and acetyl CoA molecules are formed?

2 carbons are released



1 FADH2, NADH, and acetyl CoA are formed

Palmitate has 16 carbons. In the breakdown of this molecule, how many times is it cut and how many acetyl CoA molecules are formed? Why?

It is cut 7 times forming 8 acetyl CoA molecules. This is because the last cut produces TWO acetyl CoA!

Palmitate has 16 carbons. In the breakdown of this molecule, how many times is it cut and what is the total energy yield?

It is cut 7 times and produces 106 ATP molucules

How many ATPs per acetyl CoA in the citric acid cycle?

10

How are odd-numbered fatty acids broken down?

An enzyme using vitamin B12 as a cofactor adds 1 carbon to the left over 3-carbon fragment

How are unsaturated fatty acids broken down?

Enzymes move double bonds to be in register with the beta oxidation pathway

Excess acetyl CoA is converted into what 3 thing? What are these referred to as?

1. Acetoacetate


2. 3-hydroxybutyrate


3. Acetone



They are referred to as KETONE BODIES

Ketone bodies are released into the blood for what purpose?

To be used by some tissues as fuel instead of glucose

Ketone body synthesis takes place where?

Mitochondria of the liver

In the formation of ketone bodies, what are the 5 steps?

1. acetyl CoA to Acetoacetyl CoA


2. 3-hydroxy-3-methyl-glutaryl CoA


3. Acetoacetate


4. 3-hydroxybutyrate OR Acetone

Acetone, under starvation conditions, can be captured to do what?

Synthesize glucose

3-Hydroxybutyrate can be oxidized to form what?

TWO molecules of acetyl CoA (which goes on into the citric acid cycle)

Fatty acid synthesis occurs where and by how many carbon atoms at a time?

In the cytoplasm by 2 carbon atoms at a time

What is the reducing agent of fatty acid synthesis?

NADPH

What is the raw material of fatty acid synthesis?

Acetyl CoA

How are acetyl CoA transported out of the mitochondria and into the cytoplasm so that fatty acids can be synthesized?

Acetyl CoA is converted into citrate via condensation with oxaloacetate

What is the activated form of acetyl CoA?

Malonyl CoA

Fatty acid synthesis starts with what?

The carboxylation of acetyl CoA to malonyl CoA

What is the first committed step in fatty acid synthesis?

Acetyl CoA with HCO3- to form Malonyl CoA

What are the 2 steps of malonyl CoA synthesis?

1. Acetyl CoA carboxlylase containing BIOTIN hydrolyzes acetyl CoA


2. Activated CO2 group is then transferred to form malonyl CoA

Fatty acids are synthesized by the repetition of what 4 reactions?

1. Condensation


2. Reduction


3. Dehydration


4. Reduction

The elongation phase of fatty acid synthesis in bacteria starts when acetyl CoA and malonyl CoA react with what? What is formed?

A scaffold protein called acyl carrier protein (ACP) which forms acetyl ACP and malonyl ACP

In the 1st round of fatty acid synthesis, acetyl ACP and malonyl ACP form what by what process?

Acetoacetyl ACP via CONDENSATION

Acetoacetyl ACP forms what by what process? What does it use?

D-3-hydroxybutyrl ACP via REDUCTION using NADPH

D-3-hydroxybutyrl ACP forms what by what process?

Crotonyl ACP via DEHYDRATION

Crotonyl ACP forms what by what process? What does it use?

Butyryl ACP (4-carbons) via REDUCTION using NADPH

All the carbon atoms of fatty acids containing an EVEN number of carbon atoms are derived from what?

Acetyl CoA

What two things start the 2nd round of fatty acid synthesis?

Butyryl ACP (4 C) and Malonyl ACP

Half of the NADPH needed for fatty acid synthesis comes from where? Where does the other half come from?

Half comes from the pentose phosphate pathway



Other half comes from mitochondrial export of acetyl CoA when Malate is converted into Pyruvate

After the formation of acetyl CoA, the resulting oxaloacetate is transported back into the mitochondria to form what?

NADPH

Both triacylglycerol and phospholipid synthesis begin with what precursor?

Phosphatidate

Phosphatidate is formed by the addition of what?

2 fatty acids to glycerol 3-phosphate

Fats and phospholipids connect to glycolysis via what?

Glycerol 3-phosphate

What are the 2 steps to make phosphatidate? Via what?

1. Glycerol 3-phosphate to lysophosphatidate (via saturated acyl CoA)


2. Lysophosphatidate to phosphotidate (via unsaturated acyl CoA)

What are the 2 steps to make triacylglycerol?

1. Phosphatidate to Diacylglycerol (DAG) (via hydrolysis)


2. DAG to triacylglycerol (via acyl CoA)

What are the 2 ways to make phospholipids?

1. Biosynthesis from the activation of phosphatidase by CTP



2. Biosynthesis from the activation of the "head group" of DAG by CTP

Activation of phosphatidate to CDP-diacylglycerol is driven forward by what?

The hydrolysis of pyrophosphate!

What are the 3 steps to form phosphatidylethanolamine?

1. Ethanolamine to Phosphorylethanolamine


2. CDP-ethanolamine


3. Phosphatidylethanolamine

What is the role of CTP activation in the formation of phosphatidylethanolamine?

CTP activates the alcohol phosphorylethanolamine to form CDP-ethanolamine

Phosphatidylcholine is synthesized from phosphatidylethanolamine how? Why?

It is methylated with S-Adenosylme-thionine 3 times when dietary choline is insufficient.

Sphingolipids are synthesized from what?

Ceramide

All 27 carbon atoms of cholesterol are derived from what?

Acetyl CoA

What is the 3 stage synthetic process of cholesterol?

1. Isopentenyl pyrophosphate synthesis


2. Condensation of 6 isopentenyl pyrophosyhtate molecules to form squalene


3. Squalene cyclizes into cholesterol

The formation of isopentenyl pyrophosphate from acetyl CoA starts with the formation of what?

3-hydroxy-3-methylglutaryl CoA (HMG CoA) from acetyl CoA and acetoacetyl CoA

What is the role of HMG CoA Reductase?

It catalyzes the formation of mevalonate from 3-hydroxy-3-methylglutaryl CoA in Cholesterol formation.

What is mevalonate?

An important intermediate formed from HMG CoA in the formation of cholesterol

What is the committed step of cholesterol biosynthesis?

Formation of mevolonate

In the Cytosol, HMG-CoA forms what?

Cholesterol

In the mitochondria, HMG-CoA forms what?

Ketone bodies

What is the building block of cholesterol biosynthesis?

Isoprene

Mevalonate is converted into what in 3 consecutive ATP reactions?

3-isopentenyl pyrophosphate

Squalene (30 C) is synthesized from 6 molecules of what?

Isopentenyl pyrophosphate (5 C)

What must happen to isopentenyl pyrophosphate before condensation can take place?

It must isomerize into dimethylallyl pyrophosphate

Farnesyl pyrophosphate is converted into what using what?

Squalene using farnesyl pyrophosphate and NADPH

Cholesterol and other lipids in excess of those needed by the liver are exported in what form?

Low density lipoproteins (LDLs)

Liver and peripheral-tissue cells take up LDL by what?

Receptor-mediated endocytosis

What does the LDL receptor do?

Binds LDL and mediates its entry into the cell

The absence of LDL receptors in the homozygous form of familial hypercholesterolemia leads to what?

Elevated plasma levels of LDL cholesterol and the deposition of cholesterol in blood vessels leading to heart attacks.

Homozygous familial hypercholesterolemia can only be treated by what?

A liver transplant

What is the major carrier of cholesterol in the blood?

Low-density lipoprotein

What 4 things surround the LDL?

1. Unesterified cholesterol


2. Phospholipid


3. Cholesteryl ester


4. Apoprotein B-100

What is the purpose of Apoprotein B-100?

Directs LDL to the proper cells

What is the role of LDL?

Transport cholesterol to peripheral tissues and regulate de novo cholesterol synthesis at these sites

What are the 3 steps to receptor-mediated endocytosis of LDL?

1. LDL binds to receptor protein on cell surface


2. Cell internalizes the receptor-LDL complex


3. LDL is hydrolyzed in lysosomes

What are the 2 steps to amino acid catabolism?

1. Remove alpha-amino group


2. Deliver carbon "skeleton" to glycolysis and/or citric acid cycle for oxidation

The carbon skeleton of alanine (once the NH4 is removed) is what?

Pyruvate!

The alpha amino group of many amino acids is transferred to what to form what? What happens next?

To alpha-ketoglutarate to form glutamate which is then oxidatively deaminated to yield ammonium (NH4+)

What catalyzes the transfer of an alpha-amino group from an alpha amino acid to an alpha-ketoacid?

Aminotransferases!

What does aspartate aminotransferase do?

Transfers the alpha-amino group of aspartate to alpha-ketoglutarate to form oxaloacetate and glutamate AND VICE VERSA

What happens to the nitrogen atom that is transferred to alpha-ketoglutarate in the transamination reaction?

It is converted into free ammonium ion by the oxidative deamination of glutamate, regenerating alpha-ketoglutarate

How is nitrogen removed from glutamate?

Glutamate dehydrogenase

Which amino acids can be directly converted into ammonium ion? By what?

Serine and threonine by serine and threonine dehydratase, respectively.

During fasting or exercise, muscle can use amino acids as fuel, exporting nitrogen as what?

Alanine

If pyruvate is exported as alanine without reoxidizing NADH by forming lactate, how can glycolysis continue?

NADH is oxidized by the citric acid cycle

What 6 amino acid carbon skeletons can feed into pyruvate of the citric acid cycle?

1. Alanine


2. Cysteine


3. Glycine


4. Serine


5. Threonine


6. Tryptophan

What 2 amino acid carbon skeletons can feed into oxaloacetate of the citric acid cycle?

1. Asparagine


2. Aspartate

What 3 amino acid carbon skeletons can feed into fumarate of the citric acid cycle?

1. Aspartate


2. Phenylalanine


3. Tyrosine

What 4 amino acid carbon skeletons can feed into Succinyl CoA of the citric acid cycle?

1. Isoleucine


2. Methionine


3. Threonine


4. Valine

What 5 amino acid carbon skeletons can feed into alpha-ketoglutarate of the citric acid cycle?

1. Arginine


2. Glutamate


3. Glutamine


4. Histidine


5. Proline

Where do the nitrogen atoms of urea come from? Where does the carbon atom come from?

One N comes from aspartate, the other comes from free ammonium ions



The C comes from HCO3- (derived from the hydration of CO2)

The urea cycle begins in the mitochondria with the coupling of what 2 things to form what?

Free NH4+ and HCO3- to form carbamoyl phosphate

What are the 3 steps to form carbamoyl phosphate? What catalyzes all of these reactions?

1. Bicarbonate to carboxyphosphate


2. Carboxyphosphahte to Carbamic acid


3. Carbamic acid to carbamoyl phosphate



Catalyzed by carbamoyl phosphate synthetase

The carbamoyl group of carbamoyl phosphate is transferred to what to form what? What catalyzes it?

Transferred to ornithine to form citrulline via ornithine transcarbamoylase

What are the 4 steps to the Urea Cycle starting with Citrulline?

1. Citrulline (w/ Aspartate) forms Argininosuccinate


2. Argininosuccinate to Arginine (releasing Fumarate)


3. Arginine to Ornithine (releasing UREA)


4. Ornithine (w/ Carbamoyl Phosphate) to Citrulline

Ammonia is carried on what activated molecule that then goes on to form carbamoyl phosphate?

Bicarbonate!

Urea is produced by removing Nitrogen from what?

Arginine

TRUE OR FALSE: The urea cycle only spans one compartment, the mitochondrial matrix.

FALSE. It spans both the cytoplasm and the mitochondrial matrix

Fumarate from the urea cycle can go on to make what? What can it also do?

Glucose via gluconeogenesis



OR



it can enter the citric acid cycle

Cytoplasmic malate enters the matrix and exits as what?

Aspartate

What 2 things can happen to oxaloacetate?

1. Converted into glucose via gluconeogenesis


2. Transaminated to aspartate

The carbon skeletons of amino acids are funneled into what 7 molecules?

1. Pyruvate


2. Acetyl CoA


3. Acetoacetyl CoA


4. Alpha-ketoglutarate


5. Succinyl CoA


6. Fumarate


7. Oxaloacetate

Amino acids that are degraded into acetyl CoA or acetoacetyl CoA are called what? Why?

Ketogenic amino acids because they can give rise to ketone bodies or fatty acids and CANNOT be used to synthesize glucose

Which 2 amino acids are SOLELY ketogenic?

Leucine and lysine

Which 5 amino acids are both ketogenic and glucogenic?

1. Threonine


2. Isoleucine


3. Phenylalanine


4. Tryptophan


5. Tyrosine

Atmospheric nitrogen is converted into what?

Ammonia

Ammonium + alpha-ketoglutarate --> ???

Glutamate

Glutamate + alpha-keto acid --> ???

Alpha-ketoglutarate + amino acid

What is biological nitrogen fixation?

Conversion of atmospheric nitrogen into

What is industrial nitrogen fixation?

Conversion of atmospheric nitrogen into ammonia carried out at 500 C and 300 atm pressure using Fe catalyst (Haber process)

Biological nitrogen fixation is catalyzed by what?

Nitrogenase

Glutamate synthesis is catalyzed by what?

Glutamate dehydrogenase (which is the same enzyme used in both degadation and biosynthesis of amino acids)

How is glutamate synthesized?

Alpha-ketoglutarate and ammonium is dehydrolyzed then protonated to form glutamate.

What are the 2 basic steps to form glutamine?

1. Glutamate to acyl-phosphate intermediate


2. acyl-phosphate intermediate to glutamine

Glutamate is converted into acyl-phosphate intermediate using what?

ATP

Acyl-phosphate intermediate is converted into glutamine using what? What is released?

NH3 which releases an inorganic phosphate

What 3 things are formed from 3-phosphoglycerate?

1. Serine


2. Cysteine


3. Glycine

What is tetrahydrofolate?

Coenzyme essensial for the synthesis of amino acids that is a carrier of activated 1-carbon units.

What are the 3 groups of tetrahydrofolate?

1. a substituted pteridine


2. p-aminobenzoate


3. 1+ glutamate residue chain

In the formation of glycine, the side chain methylene group of serine is transferred to what?

Tetrahydrofolate, a carrier of one-carbon units

What are the 9 essential (CANNOT be synthesized) amino acids?

1. Histidine


2. Isoleucine


3. Leucine


4. Lysine


5. Methionine


6. Phenylalanine


7. Threonine


8. Tryptophan


9. Valine

TRUE OR FALSE: Non-essential amino acids have complex pathways.

FALSE. They have simple pathways.

Alpha-ketoglutarate goes to glutamate which goes to what 3 amino acids?

1. Glutamine


2. Proline


3. Arginine

Pyruvate makes what 3 amino acids?

1. Alanine


2. Valine


3. Leucine

Oxaloacetate goes to aspartate which can make what 5 amino acids?

1. Asparagine


2. Methionine


3. Threonine


4. Isoleucine (From threonine)


5. Lysine

What are the 3 steps to make serine?

1. 3-phosphoglycerate to 3-phosphohydroxypyruvate


2. 3-phosphoserine


3. Serine

How is 3-phosphoglycerate converted into 3-phosphohydroxypyruvate?

It's oxidized via NAD+ (forming NADH)

How is 3-phosphohydroxypyruvate converted into 3-phosphoserine?

Transamination via glutamate (forming alpha-ketoglutarate)

How is 3-phosphoserine converted into serine?

Hydrolysis!

The one-carbon group carried by tetrahydrofolate is bonded to what?

Tetrahydrofolate's N-5 or N-10 or to both!

The most reduced form of tetrahydrofolate carries what? What does the intermediate carry?

A methyl group



The intermediate carries a methylene group

The most oxidized form of tetrahydrofolate can carry what 3 things?

1. Formyl


2. Formimino


3. Methenyl groups

The fully oxidized one carbon unit, CO2, is carried by what rather than by tetrahydrofolate?

Biotin!

What is the major donor of methyl groups?

S-adenosylmethionine (SAM)

SAM is synthesized by what?

The transfer of an adenosyl group from ATP to the sulfur atom of methionine

How is serine converted into glycine?

Tetrahydrofolate removes the side chain of serine to produce glycine and N5,N10-methylenetetrahydrofolate.

Along with NADPH, N5,N10-methylenetetrahydrofolate is converted into what for further methylation reactions?

N5-methyltetrahydrofolate

Methionine + ATP ---> ???

S-Adenosylmethionine + Pi + PPi

Methionine is regenerated from what?

N5-Me-THF and Homocysteine

Serine inhibits its own synthesis at what point?

The oxidation reaction between 3-phosphoglycerate and NAD+

What are the 2 pathways of nucleotide biosynthesis?

1. De novo


2. Salvage

What is De novo?

Nucleotide synthesis built up from small precursors

What is Salvage?

Nucleotide recovery from other reactions and added to ribose

In pyrimidine synthesis, N1 and C4,5,6 come from where?

Aspartate

In pyrimidine synthesis, C2 and N3 come from where?

Carbamoyl phosphate

What are the 3 precursors of pyrimidine rings?

1. Bicarbonate


2. Aspartic acid


3. Ammonia

What are the 3 steps of carbamoyl phosphate synthesis? Where do all three steps occur?

1. Bicarbonate to Carboxyphosphate (ATP)


2. Carboxyphosphate to Carbamic Acid (NH3 from Gln)


3. Carbamic Acid to Carbamoyl Phosphate (ATP)



All three steps occur on carbamoyl phosphate synthase!

In pyrimidine nucleotide synthesis, what are the 3 acts?

1. Pyrimidine ring formation


2. Attachment to ribose phosphate


3. 2' deoxy

The Urea cycle uses which carbamoyl phosphate synthase?

CPS-1: NH3 from ammonium

Pyrimidine synthesis uses which carbamoyl phosphate synthase?

CPS-2: NH3 from glutamine

What is 5-phosphoribosyl-1-pyrophosphate (PRPP)? How is it synthesized?

Activated ribose for base attachment that is synthesized from ribose 5-phosphate (from the pentose phosphate pathway).

Deoxyribonucleotide synthesis is catalyzed by what?

Ribonucleotide reductase

In deoxyribonucleotide synthesis, deoxyribonucleotides are made via what mechanism?

Cysteine free radical mechanism

Oxidized cysteines are reduced by what in Deoxyribonucleotide synthesis?

NADPH

What is the role of tetrahydrofolate in the formation of thymidylate?

N5,N10-methylenetetrahydrofolate is the methyl donor for deoxyuridine monophonphate (dUMP) that creates thymidylate (TMP) and dihydrofolate.

Dihydrofolate, which is made during thymidylate synthesis, is reduced to form what?

Tetrahydrofolate via dihydrofolate reductase and NADPH

Carbamoyl phosphate is converted into what in nucleotide synthesis?

Carbamoylaspartate via aspartate and aspartate transcarbamoylase

Carbamoylaspartate is converted into what?

Orotate (NADH is formed as well)

Orotate reacts with what to form what?

Reacts with PRPP to form orotidylate, a pyrimidine nucleotide

Orotidylate is then decarboxylated via what to form what?

Uridylate (Uridine Monophosphate, UMP) via orotidylate decarboxylase

How is cytidine monophosphate (CMP) formed?

UMP is converted to UTP via ATP, then UTP's carbonyl group is replaced by an amino group donated by glutamine to form CTP.