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203 Cards in this Set

  • Front
  • Back
What are the four major classes of biomolecules?
Carbohydrates, proteins, lipids, and nucleic acids
What are the two classes of carbohydrates?
Ketose and Aldose
What are the three simplest carbohydrates?
Dihydroxyacetone (ketose) and D- and L-Glyceraldehyde (aldose)
O-glycosidic bonds link what carbons from two different carbohydrates?
C1 --> C4
What is the purpose of glycogen?
To store glucose in the body.
What type of bond in glycogen is responsible for branching?
alpha-1,6-glycosidic bond, every 10 units
What type of linkage makes up cellulose?
beta-1,4-linkages, in comparison to glycogen who has alpha-1,4-linkages
What are glycosaminoglycans?
They are negatively charged polymers
Found on the cell surface and in the extracellular matrix
They are a type of modification
What are glycoproteins?
They are proteins that are modified to have carbohydrates on them.
What are the two different glycosidic bonds in glycoproteins?
1. N-linked to the protein
2. O-linked to the protein
Where are N-linked carbohydrates of the glycoprotein made and altered?
They are made in the ER and they are altered in the Golgi Complex
Where are O-linked carbohydrates of the glycoprotein made and altered?
They are made and altered in the Golgi Complex
What is the purpose of adding mannose-6-phosphate to enzymes?
To direct the enzymes to lysosomes.
How does a mannose residue become a mannose-6-phosphate residue?
Mannose is transfered to mannose-6-phosphate in order to be added to enzymes, to direct them towards lysosomes.

REACTION:
Mannose residue ---(phosphotransferase)---> Intermediate ---(phosphodiesterase)---> mannose-6-phosphate residue
What are lectins?
They are proteins that bind to specific carbohydrate structures (that are on cell surfaces).

The main function is to promote cell-cell contact.
What is the basic (very basic!) pathway of glucose metabolism?
Glucose ---> Pyruvate ---> Lactate(anaerobic) or Acetyl CoA (aerobic)
What are three reasons we need energy?
1. To perform work through muscle contractions and cellular movement

2. To actively transport molecules and ions (transports them against concentration gradient)

3. The make biomolecules from simple precursors
In order to metabolize glucose, what are the two requirements?
1. The reaction is specific, only yield one product or set.

2. The reaction is thermodynamically favored.
What are the two different forms of metabolism?
1. Catabolism, break down molecules into smaller units and release energy.
For example, polysaccharides into monosaccharides, lipids into fatty acids, nucleic acids into nucleotides, and proteins into amino acids

2. Anabolism - Make molecules from smaller units, energy is needed for this. Opposite of catabolism
What three units is ATP made of?
1. Three phosphate groups
2. ribose
3. adenine
How do you make ATP?
Adding together ADP (adenine diphosphate) and orthophosphate
How much energy is released from the hydrolysis of ATP to ADP?
Change in G = -7.3 kcal/mole
How much energy is released from the hydrolysis of ATP to AMP?
Change in G = -10.9 kcal/mole
What are three reasons why ADP + P is more stable than ATP + H2O?
1. Resonance stabilization of orthophosphate - prthophosphate has 4 different resonance structures, which makes it very stable.

2. Electrostatic repulsion in ATP - it has four negative charges that all repel each other.

3. Stabilization due to hydration - water can bind to ADP and P better than phosphate in ATP.
What are the three stages of catabolism?
Stage 1 - large molecules get broken up (prep stage). Fats get broken into fatty acids and glycerol, polysaccharides get broken into glucose and other sugars, and proteins get broken into amino acids.

Stage 2 - small molecules get degraded into a few simple units that play a central role in metabolism, aka, Acetyl CoA

Stage 3 - ATP is produced from oxidation of acetyl unit from acetyl CoA, citric acid cycle and oxidative phosphorylation
What is the role of NAD+?
It acts as an electron carrier in the oxidation of fuel molecules, NADH.

It is a coenzyme.
What is the role of FAD?
It acts like an electron carrier, FADH.

It is a coenzyme.
What are the role of vitamins?
Vitamins are precursors to coenzymes
What does glycolysis do?
It forms two pyruvates from one glucose. It also forms two ATP.
What are the three different stages of glycolysis?
Stage 1 - glucose is trapped and destabilized: Glucose --> frutose-1,6-bisphosphate

Stage 2 - Two 3-C molecules are made from the cleavage of a 6-C fructose: Fructose-1,6-bisphosphate ---> dihydroxyacetone phosphate and glyceraldehyde 3-phosphate

Stage 3 - ATP is generated, 2 units of glyceraldehyde 3-phosphate (DHAP gets changed to this so there are 2 units) ---> pyruvate
What are the three (general) steps to change glucose into fructose-1,6-bisphosphate?
1. Phosphorylation
2. Isomerization
3. Second phosphorylation
What is the specific reaction pathway of stage 1 of glycolysis?
Glucose ---(hexokinase)---> glucose-6-phosphate ---(phosphoglucose isomerase)---> fructose-6-phosphate ---(phosphofructokinase)--->fructose-1,6-bisphosphate

1. Glucose phosphorylated by ATP to form glucose-6-phosphate
2. Isomerization
3. fructose-6-phosphate is phosphorylated by ATP to form fructose-1,6-bisphosphate
What enzyme converts glucose to glucose-6-phosphate?
hexokinase
What enzyme converts glucose-6-phosphate to fuctose-6-phosphate?
phosophoglucose isomerase
What enzyme converts fructose-6-phosphate to fructose-1,6-bisphosphate?
phosphofructokinase (PFK)
What is the specific reaction pathway of stage 2 in glycolysis?
Fructose-1,6-bisphosphate ---(aldolase)---> dihydroxyacetone phosphate (DHAP) + glyceraldehyde 3-phosphate (GAP)
In stage 2 of glycolysis, which product is on the direct pathway of glycolsis and which is not?
Glyceraldehyde 3-phosphate is on the direct pathway.

Dihydroxyacetone phosphate is not, it must be converted to glyceraldehyde 3-phosphate
What enzyme converts dihydroxyacetone phosphate to glyceraldehyde 3-phosphate?
triose phosphate isomerase (TIM)
What is the mechanism for TIM changing DHAP into GAP?
1. Glu acts as a base and take a proton from C-1 of DHAP. His acts as an acid and donates proton to the O on C-2.

2. Glumatic acid donates proton to C-2 and his takes proton from the -OH on C-1.

3. GAP is formed
What is the specific reaction pathway of stage 3 in glycolysis?
Glyceraldehyde 3-phosphate---(glyceraldehyde 3-phosphate dehydrogenase)---> 1,3-bisphosphoglycerate---(phosphoglycerate kicase)--> 3-phosphoglycerate ---(phosphoglycerate mutase)---> 2-phosphoglycerate ---(enolase)---> phosphoenolpyruvate ---(pyruvate kinase)---> pyruvate

*Note the reaction starts with 2 glyceraldehyde 3-phophates, so 2 pyruvates are formed along with 2 ATP and 2 NADH.
What enzyme forms 1,3-bisphosphoglycerate from glyceraldehyde 3-phosphate?
glyceraldehyde 3-phosphate dehydrogenase
What enzyme forms 3-phosphoglycerate from 1,3-bisphosphoglycerate?
phosphoglycerate kinase
What enzyme forms 2-phosphoglycerate from 3-phosphoglycerate?
phosphoglycerate mutase
What enzyme forms phosphoenolpyruvate from 2-phosphoglycerate?
enolase
What enzyme forms pyruvate from phosphoenolpyruvate?
pyruvate kinase
What step of glycolysis forms NADH?
When glyceraldehyde 3-phosphate is made into 1,3-bisphosphoglycerate from glyceraldehyde 3-phosphate dehydrogenase
How does galactose enter the glycolytic pathway?
It converts into glucose-6-phosphate and then proceeds
How does fructose enter the glycolytic pathway?
It converts to fructose-6-phosphate and then proceeds
What is the key to regulating glycolysis?
Regulating phosphofructokinase (PFK)
Why is the regulation of PFK most important to regulating glycolysis?
This is where the first irreversible step occurs.
What are the three irreversible steps of glycolysis?
1. Fructose-6-phosphate ---(phosphofructokinase)---> Fructose-1,6-bisphosphate

2. Fructose-1,6-bisphosphate ---(aldolase)---> dihydroxyacetone phosphate + glyceraldehyde 3-phosphate

3. Phosphoenolpyruvate ---(pyruvate kinase)---> pyruvate
How is glycolysis regulated?
1. High energy charge inhibits phosphofructokinase and pyruvate kinase.

2. When PFK is turned off, increase in fructose-6-phosphate which increase glucose-6-phosphate. The increased concentration of glucose-6-phosphate inhibits hexokinase, so less glucose-6-phosphate is produced.
How does glycolysis regulation work in a rest/excercise model?
At rest, there is a high concentration of ATP, so glycolysis will not be active because PFK shuts down.

During excercise, ATP decreases because muscle contraction uses energy, so the low energy charge activates PFK which starts up glycolysis.
What is cellular respiration?
This is the combination of the citric acid cycle and oxidative phosporylation, which generates large quantities of ATP.
What two things enter the Citric Acid Cycle?
Acetyl CoA and Oxaloacetate
Where does cellular respiration take place?
The matrix of the mitochondria
What is the function of the citric acid cycle?
To harvest high energy electrons for oxidative phosphorylation to generate ATP.
How and where is pyruvate converted to acetyl CoA?
In the mitochondrial matrix, it is oxidatively decarboxylated by pyruvate dehydrogenase complex to form acetyl CoA
What are the three enzymes that make up the pyruvate dehydrogenase complex?
1. Pyruvate dehydrogenase component, E1

2. Dihydrolipoyl transacetylase, E2

3. Dihydrolipoyl dehydrogenase, E3
How many coenzymes make up the pyruvate dehydrogenase complex and what are they?
There are 5:
1. Thiamine pyrophosphate (TPP)
2. Lipoic Acid
3. FAD
4. Coenzyme A (CoA)
5. NAD+
For each acetyl CoA unit, what does the citric acid cycle generate?
3 NADH
1 GTP
1 FADH2
What is the first step of the citric acid cycle?
Acetyl CoA + Oxaloacetate ---(Citrate Synthase)---> Citryl CoA -----> Citrate
What is the order of binding to citrate synthase?
First oxaloacetate binds then acetyl CoA.
What is the specific reaction pathway of the citric acid cycle?
Oxaloacetate + Acetyl CoA ---(Citrate Synthase)---> Citrate ---(aconitase)---> cis-Aconitate[inter.] ---(aconitase)---> Isocitrate ---(isocitrate dehydrogenase)---> oxalosuccinate[inter.] ---(isocitrate dehydrogenase)---> alpha-Ketoglutarate ---(alpha-Ketoglutarate Dehydrogenase)---> Succinyl CoA ---(succinyl CoA synthetase)---> Succinate ---(succinate dehydrogenase)---> Fumarate ---(fumarase)---> Malate ---(malate dehydrgenase)---> Oxaloacetate

*Regeneration of oxaloacetate is critical for CAC to continue on*
Oxaloacetate + Acetyl CoA ---(?)---> Citrate
citrate synthase
Citrate ---(?)---> Isocitrate
aconitase
Isocitrate ---(?)---> alpha-Ketoglutarate
Isocitrate dehydrogenase

*Forms NADH*
alpha-Ketoglutarate ---(?)---> Succinyl CoA
alpha-Ketoglutarate dehydrogenase complex

*Forms NADH*
Succinyl CoA ---(?)---> Succinate
Succinyl CoA synthetase

*Forms GTP*
Succinate ---(?)---> Fumarate
Succinate dehydrogenase

*Forms FADH2*
Fumarate ---(?)---> Malate
Fumarase
Malate ---(?)---> Oxaloacetate
Malate dehydrogenase

*Forms NADH*
What is the purpose of the pentose-phosphate pathway?
It generates NADPH and makes 5-C sugars
Where does the reaction of the pentose-phosphate pathway occur?
The cytoplasm
What are the two phases of the pentose-phosphate pathway?
Phase 1 - Oxidative, generate NADPH

Phase 2 - Non oxidative, interconverts phosphorylated sugars
What is gluconeogenesis?
It is the synthesis of glucose from compounds other than carbohydrate.
What are the three different carbohydrate precursors involved in gluconeogenesis?
1. Lactate (from glycolysis)
2. Amino Acids (from protein)
3. Glycerol (from fat)
What is the purpose of gluconeogenesis?
1. To maintain blood glucose levels (very important for the brain)

2. Maintains blood glucose levels during times of need (fasting or starvation)
Where does gluconeogenesis take place?
Primarily in the liver, but also in the kidney.
What is the basic pathway of gluconeogenesis?
Pyruvate (from lactate) ----> oxaloacetate (or starts here from amino acids) ----> dihydroxyacetone phosphate (or starts here from glycerol) ----> glucose
What are the bypass steps in gluconeogenesis?
1. Pyruvate ---(pyruvate carboxylase)---> oxaloacetate ---(phosphoenolpyruvate carboxykinase)---> phosphoenolpyruvate

2. Fructose-1,6-bisphosphate ---(fructose 1,6-bisphosphotase)---> fructose-6-phosphate

3. Glucose-6-phosphate ---(glocose-6-phosphotase)---> glucose

*In many tissues, gluconeogenesis stops at glucose-6-phosphate; it can be converted to glycogen for storage.
Pyruvate ---(?)---> Oxaloacetate
Pyruvate carboxylase
Oxaloacetate ---(?)---> Phosphoenolpyruvate
Phosphoenolpyruvate carboxykinase
Where does the pyruvate ---> phosphoenolpyruvate reaction take place?
1. Pyruvate to Oxaloacetate takes place in the mitochondria.

2. oxaloacetate ---> phosphoenolpyruvate takes place in the cytoplasm.

Oxaloacetate must convert to malate to leave the mitochondria, and then converts back to oxaloacetate
Fructose-1,6-bisphosphate ---(?)---> Fructose-6-phosphate
fructose-1,6-bisphosphotase
Glucose-6-phosphate ---(?)---> Glucose
glucose-6-phosphotase
What 4 factors regulate (stimulate) phosphofructokinase?
1. Increase in AMP
2. Decrease in ATP
3. Decrease in citrate
4. Increase in protons

*Low energy charge
What 2 factors regulate (stimulate) fructose-1,6-bisphosphotase?
1. Decrease in AMP
2. Increase in citrate

*High energy charge
What 2 factors regulate (stimulate) pyruvate kinase?
1. Decrease in ATP
2. Decrease in alanine

*Low energy charge
What factor regulates (stimulate) phosphoenolpyruvate carboxylase?
1. Decrease in ADP

*High energy charge
What does glucagon do?
It rises after fasting. This is the signal that gluconeogenesis is needed. It also inhibits glycolytic enzymes.
What does insulin do?
It rises after eating. This is the signal that there is alot of glucose in the body and that glycolysis can be turned on. It stimulates PFK and pyruvate kinase.
What does the Cori cycle do?
It links glycolysis in the muscle with gluconeogenesis in the liver.
What is the cofactor for pyruvate carboxylase?
biotin
What is the allosteric regulator for pyruvate carboxylase?
acetyl CoA
Where does glycogen degradation take place?
In muscle and cardiac muscle in order to provide glucose to energize cells.
What are the two ways that glucose can be stored?
1. Glycogen

2. Fats (as triacylglycerol)
Where are sites of glycogen storage?
Liver and skeletal muscle.
What is the significance of branching?
1. There are more non-reducing ends available.

2. It increases solubility.
What are the three basic steps of glycogen degradation?
1. Release glucose-1-phosphate from 1,4-linked phosphate.

2. Remodeling of 1,6-branches to allow further degradation.

3. Conversion of glucose 1-phophate to glucose-6-phosphate for metabolism

glycogen ---> glucose-6-phosphate
Glycogen ---(?)---> glucose-1-phosphate
glycogen phosphorylase
What are the advantages of phosphorylysis of glycogen rather than hydrolysis (adding water to glycogen, which would then make glucose directly)?
1. It is energetically favorable.

2. Muscle cells do not have the transporters for glucose 1-phosphate, so it can not be transported into the blood and has to stay in the muscle.
What is the coenzyme for glycogen phosphorylase?
Pyridoxal phosphate
What is the first step of the phosphorylase of glycogen to glucose 1-phosphate (a carbocation intermediate forms)?
1. PLP donates a proton onto the free phosphate of HPO42- (in the solution also).

2. Phosphate donates a proton to glycogen.

3. Bond is broken from gluose carbocation and glycogen (n-1).
What is the second step of the phosphorylation of glycogen to glucose 1-phosphate (Attacking the carbocation)?
1. Carbocation is unstable.

2. Carbocation is attacked by phosphate; which yields glucose 1-phosphate and PLP.
Explain the 3 different enzymes that are involved in glycogen degradation.
1. Glycogen phosphorylase cleave alpha-1,4-glycosidic bonds until there are 4 left before an alpha-1,6,-glycosidic bond.

2. A transferase transfers 3 of the glucosyls on the alpha-1,6,-branch to the alpha-1,4-branch.

3. Alpha-1,6,-glucosidase removes the last residue left at the alpha-1,6-branch, which leaves just a linear chain left. Glycogen phosphorylase will now be able to cleave all of this.
Glucose 1-phosphate ---(?)---> glucose-6-phosphate
Phosphoglucomutase
What are the three fates of glucose-6-phosphate?
1. Glycolysis, it is fuel

2. It goes into the blood, for use by other tissues (has to be converted to free glucose in order to go into the blood stream)

3. Pentose-Phosphate pathway (this yields NADPH and a 5-C molecule).
What is the key regulatory point for glycogen degradation?
Glycogen phosphrolyase
What two factors is glycogen phosphorylase regulated by?
1. Allosteric effectors (energy charge, glucose)

2. Hormones (insulin, epinephrine, glucagon)
What are the two forms of glycogen phosphorylase?
1. Phosphorylase a - usually active and favors the R form.

2. Phosphorylase b - usually inactive, and favors the T form

a and b interconverted by phosphorylation (hormone regulation)

R and T interconverted by allosteric factors (energy charge)
When is phosphorylase b active (in the R form)?
When there is high concentrations of AMP, low energy charge.
Where is phosphorylase b located?
muscle
Where is phosphorylase a located?
liver
What regulates phosphorylase a in the liver?
Glucose, when there are high concentrations of it, it is inactive. This is because glycogen degradation to glucose is no longer needed at that time.
What enzyme catalyzes phosphorylase b to a?
Phosphorylase kinase
How is phosphorylase kinase activated?
The beta subunit must be phosphorylated AND calcium ion binding to the delta subunit
What do glucagon and epinephrine regulate?
Glucagon regulates glycogen degradation in liver.

Epinephrine regulates glycogen degradation in muscle.
What glucose transporters increase because of signals from insulin?
GLUT4, insulin signals the fed state, so it promotes the uptake of glucose.
After glucose is taken up into the cell, it is phosphorylated to Glucose 6-phosphate by what enzyme?
Glucokinase (in the liver)
or
Hexokinase (everywhere else)
What are the three basic pathways of glycogen synthesis?
1. It requires an activated form of glucose: UDP-glucose

2. UDP-glucose is added to the non-reducing ends of glycogen

3. Remodeling (branching) is needed for continuous synthesis
How is UDP-glucose made?
Glucose 1-phosphate + UTP ---(UDP-glucose pyrophosphorylase)---> UDP-glucose
What is UDP-glucose used for?
It is the glucose donor in glycogen synthesis.
UDP-glucose + glycogen (n residues) ---(?)---> glycogen (n+1 reisudes)
glycogen synthase

*It adds glucosyl units that has four or more residues on the chain, doesn't start the reaction.*
What is glycogenin?
The protein that starts glycogen synthesis.

It synthesizes a primer for glycogen synthesis.
What type of protein in glycogenin?
A glycosyltransferase with two identical subunits.

Each subunit catalyzes addition of glucosyl to the other, initiating at tyrosine-OH
What are the 3 requirements for the branching enzyme to branch glycogen?
1. The chain must be great than or equal to 11 residues long.

2. It must transfer a block of 7 residues

3. It must include the non-reducing terminus.
What is the key regulatory enzyme of glycogen synthesis?
glycogen synthase
What effects does phosphorylation have on glycogen synthesis and degradation?
In degradation,glycogen phosphorylase is the key regulatory enzyme and it is stimulated by phosphorylation.
It changes phosphorylase b ---> a

In synthesis, glycogen synthase is the key regulatory enzyme, and it is inhibited by phosphorylation. It changes phosphorylase a ---> b

(b is only active if there are high levels of glucose-6-phosphate)
Protein kinase _________ glycogen degradation and __________ glycogen synthesis.
activates glycogen degradation

deactivates glycogen synthesis
What is the role of protein phosphorylase 1?
It stimulates glycogen synthesis by inactivating phosphorylase a and phosphorylase kinase by dephosphorylating them.
What is protein phosphorylase 1 made up of?
1. A catalytic subunit (PP1)

2. Regulatory subunit (Gm or GL)

3. A binding site for the target enzyme
When glycogen degradation is needed, PP1 is inactivated by EPI and glucagon making protein kinase A active.

What are the two ways protein kinase A reduces PP1 activity?
1. It phosphorylates the regulatory subunit, whih releases the catalytic subunit.

2. It phosphorylates an inhibitor that inactivates PP1 catalytic activity.
What role does insulin play in glycogen synthesis?
It stimulates glycogen synthesis. by inactivating glycogen synthase kinase (which keeps glycogen synthesis in its inactive state).
What is Von Gierke disease?
Glucose 6-phosphotase is defective, so severe hyperglycemia occurs, which means no glucose is released into the blood.
What is McArdle Disease?
Muscle phosphorylase is defective, so it causes exercise-induced pain and cramps because can't break down glycogen in the muscle, so can't provide enough energy to these cells.
What is Her's Disease?
Liver phosphorylase is defective, so it causes mild hypoglycemia because blood glucose is still able to be provided b gluconeogensis.
What is Anderson's Disease?
The branching enzyme is defective, which causes liver failure and death because it will only make linear chains which causes low solubility and it will precipitate and accumulate in the liver.
What are the four major physiological roles of fatty acids?
1. fuels - stored as triacylglycerols

2. Building blocks of phospholipids and glycolipids - they make up membranes

3. Signals to membrane localize proteins

4. Hormones and second messengers
What are chylomicrons?
They transport triacylglycerols through the blood and deliver them to membranes

Have to degrade them to fatty acids in order to get through membranes
What are the three basic steps of degrading triacylgylcerol into energy?
1. Mobilization: release of fatty acids and glycerol.

2. Activation of fatty acids and transport into mitochondria (to be degraded)

3. Degradation of fatty acids into acetyl CoA and the production of FADH2 and NADH
Triacylglycerol ---(?)---> glycerol + fatty acids
lipase
What is the role of perilipin A?
It restructures the fat droplet so that it is readily accessible to lipases.
What is the reaction pathway of glycerol entering glycolysis/gluconeogeisis?
Glycerol ---(glycerol kinase)---> L-Glycerol 3-Phosphate ---(glycerol phosphate dehydrogenase)---> DHAP + GAP
What is the reaction pathway for fatty acid to enter the mitochondria (where it is oxidized)
Fatty Acid + coenzyme A ---(acyl coA synthetase)---> Acyl CoA
Acyl CoA is coupled with carnitine to enter the mitochondria, explain that process.
Carnitine + Acyl CoA ---(carnitine acyltransferase 1)---> acyl carnitine

Translocase shuttles acyl carnitine across the membrane
What does one round of fatty acid oxidation yield?
Acetyl CoA
A fatty acid (n-2)
FADH2
NADH
What are the four basic steps of one round of fatty acid oxidation?
1. Oxidation by acyl CoA dehydrogenase
2. Hydration by enoyl CoAhydratase
3. Oxidation by L-3-hydroxyacyl CoA dehydrogenase
4. Thiolysis by beta-ketothiolase
First Oxidation of fatty acid degradation
acyl CoA ---(acyl coA dehydrogenase)---> trans-delta-enoyl CoA

*produces FADH2
1 FADH2 = ? ATP
1.5 ATP
Hydration step of fatty acid degradation
enoyl CoA ---(enoyl CoA hydratase)---> L-3-hydroxyacyl CoA
2nd oxidation step of fatty acid degradation
L-3-hydroxyacyl CoA ---(L-3-hydroxyacyl CoA dehydrogenase)---> 3-Ketoacyl CoA

*Produces NADH
Thiolysis step of fatty acid degradation
3-ketoacyl CoA ---(beta-ketothiolase) ---> acyl coA + acetyl CoA

*Produces 10 molecules of ATP
1 NADH = ? ATP
2.5 ATP
What enzyme is needed for unsaturated fatty acids with an odd number of carbons?
isomerase
What enzymes are needed for unsaturated fatty acids with even number of carbons?
isomerase and reductase
When are ketone bodies formed?
They are formed from acetyl CoA when fat degradation predominates, aka when there is no oxaloacetate (which comes from pyruvate) available.
Where are ketone bodies used?
heart muscle cell
renal-cortex cell
brain cells during starvation
What is the reaction pathway to form ketone bodies?
2 acetyl CoA ---> acetoacytyl CoA ---> 3-Hydroxy 3-methyl-glutaryl CoA ---> Acetoacetate ---> D-3-hydroxybutyrate or acetone (ketone bodies)
What is dangerous about ketone bodies?
An excess can lead to acidosis, ketosis, coma, and then death.
What is the basic pathway of fatty acid synthesis?
1. Condensation
2. Reduction
3. Dehydration
4. 2nd Reduction
Where does fatty acid synthesis take place in comparison to degradation?
Synthesis takes place in the cytoplasm and degradation takes place in the mitochondria.
What are the intermediates attached to in synthesis in comparison to degradation?
In synthesis, the intermediates are attached to acyl CoA protein.

In degradation, intermediates are attached to coenzyme A
What is the reductant in fatty acid synthesis?
NADPH
What are the oxidants in fatty acid degradation?
NAD+ and FAD
What is the first step in fatty acid synthesis?
Acetyl CoA ---(Acetyl CoA carboxylase)---> Malonyl CoA

*Cofactor: biotin*
What is the key regulatory enzyme in fatty acid synthesis?
Acetyl CoA carboxylase
When there is a high energy charge, is acetyl CoA carboxylase acitvated or not?
It is activated, it is inactive (and phosphorylated ) under low energy charge.
How is acetyl CoA carboxylase allosterically regulated?
1. Citrate activates the enzyme by converting inactive dimers to a filamentous active form.

2. Palmitoyl CoA inhibits the enzyme (when excess in fatty acids), it promotes filamentous disassembly
What does malonyl CoA inhibit?
It inhibits carnitine transferase I, which then prevents the entry of fatty acids into mitochondria to be degraded, when there are alot of fatty acids already.
Condensation Reaction of fatty acid synthesis
Acetyl ACP + Malonyl ACP ---(Acyl-malonyl ACP condensing enzyme)---> Acetoacetyl ACP

2 + 3 = 4 + 1
1st Reduction Reaction of fatty acid synthesis
Acetoacetyl ACP ---(beta-ketoacyl ACP reductase)---> D-3-hydroxybutyryl ACP

*NADPH is reductant*
Dehydration reaction of fatty acid synthesis
D-3-hydroxybutyryl ACP ---> Crotonyl ACP
2nd reduction of fatty acid synthesis
Crotonyl ACP ---(Enoyl ACP Reductase)---> Butryryl ACP

*After more cycles of this, final product is Palmitate (16 C fatty acid)

*NADPH is reductant*

*Inhibited by triclosan, antibacterial*
What does the first domain of the fatty acid synthase include?
Acetyl Transferase
Malonyl Transferase
Condensing Enzyme (acyl-maloynl ACP condensing enzyme)
What does the second domain of the fatty acid synthase include?
Beta-ketoacyl reductase
Dehydratase
Enoyl reductase ACP
What does the third domain of the fatty acid synthase include?
thioesterase
What carries acetyl CoA from the mitochondria to the cytoplasm so that it can take part in fatty acid synthesis?
Citrate, generate NADPH when doing this.
What does triclosan inhibit?
Enoyl ACP reductase, along with isoniazi
What are the 3 common types of membrane lipids?
Phospholipids
Glycolipids
Cholesterol
What are the four components of phospholipids?
1. One or more phospholipid
2. A platform the fatty acids are attached to, the two being glycerol or sphingosine
3. A phosphate
4. An alcohol attached to the phosphate
How do glycerophospholipids differ from sphingophospholipids?
They have a different platform (glycerol for the first and sphingosine for the second).
What are the two modes of synthesis of glycerophospholipids?
Phospholipid synthesis can either be activated by a phosphatidate or an alcohol.
What are the two major fates of 3-hydroxy-3-methyl glutaryl CoA?
Either forming into mevalonate (commited step in cholesterol) in the cytoplasm or Acetyl CoA + Acetoacetate (ketone bodies) in the mitochondria.
Phospholipid synthesis with phosphatidate:
Phosphatidate + CTP ---> CDP-diacylglycerol (+ phosphatidylglycerol) ---> diphosphatidylglycerol
Phospholipic synthesis with activated alcohol:
Ethanolamine + ATP ---> Phosphorylethanolamine + CTP ---> CDP-ethanolamine (activated alcohol) + diacylglycerol ---> phosphatidylethanolamine ---> phosphatidylethanolamine
What is the intermeadiate in the synthesis with sphingolipids?
Ceramide
What is the cause of respiratory distress syndrome?
Failure in the biosynthetic pathway for dipalmitoyl phosphatidylcholine (component for lung surfactant)
Which lipid is involved in Tay-Sach's disease and what is the metabolic defect?
It is defective in a specific hexoaminidase. This removes terminal sugar of gangliosides, so neurons swell with lipid fillied lysosomes.
What type of reaction is frequently involved in the conversion of cholesterol to steroid hormones?
Oxidation and hydration
What is the source of the C atoms in cholesterol?
Acetyl CoA
What is the committed step in cholesterol biosynthesis?
3-hydroxy-3methylglutaryl CoA ---> Mevalonate
Describe the regulation at the commited step of cholesterol biosynthesis.
4 ways:

1. Rate of synthesis of reductase mRNA
2. Rate of translation of reductase mRNA
3. Degradation of the reductase protein
4. Activity of the protein is controlled by phosphorylation.
What is the key building block of cholesterol (the activated unit)?
3-isopentenyl pyrophosphate
Name 3 derivatives of cholesterol.
Steroid hormones
bile salts
Vitamin D
Which properties do lipids convey to membranes?
They give them amphipathic characteristic; they have both hydrophobic and hydrophilic properties.
Describe the characteristic feature of biological membranes.
They form a lipid bilayer and are highly impermeable to ions and most polar molecules (except water).
What regulates membrane fluidity?
Fatty acids composition and cholesterol content.
How do ions and molecules cross membranes? Compare and contrast the different modes of crossing.
Three ways; diffusion, passive transport and active transport.

Diffusion is where a molecule can easily pass through the membrane; it should be nonpolar and hydrophobic.

Passive transport is when ions and molecules pass through a channel from high concentration to low concentration.

Active transport is where ions and molecules pass through a channel from low to high concentration. energy is involved in this.
Name 2 classes of membrane proteins that confer permeability. Compare and contrast. Give examples of each.
1. Integral - interact with hydrocarbon chains and they span the membrane. they are hard to get out, need to use detergent.

Peripheral - they associate with head groups, the integral membrane proteins or they are anchored to the membrane covalently.
What is the key difference between P-type ATPases and ABC transporters?
P-type ATPases are ATP driven pumps. They function in muscle relaxation by moving Ca from the cytoplasm to the sarcoplasmic reticulum (pump Ca against concentration gradient. Conformation change (opening and closing of pump) is caused by being phosphorylated.

ABC transporters also driven by ATP pump. Stand for ATP-binding cassettes. They are not phosphorylated themselves. They conformationally change when two units of ATP bind, which causes the channel to open to allow a particle into the cell.
Discuss how the structure of the Shaker K+ channel is optimized for function. Include in your discussion the role of the selectivity filter and discuss why Na+ does not pass
through this channel.
It allows for specificity because it allows ONLY K into the channel. This is because of it's size and the energy required to strip its electrons (this factor excludes other ions that are smaller than it).

this is why Na+ can go through, because it requires alot more enrgy to strip it hydrate it than K+.
How does cholesterol regulate phospholipid fluidity?
At high temperatures, it reduces the membrane fluidity because it interacts with the hydrocarbon tails.

At low temperatures, it helps prevent gelling and so it maintains membrane fluidity.