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156 Cards in this Set

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List the coenzymes described in lecture 2.
Thiamine Pyrophosphate (B1)
Flavin Adenine Dinucleotide (B2)
Nicotinamide Adenine Dinucleotide (B3)
CoEnzyme A (B5)
Lipoate
ATP
Uridine Diposphate
List which groups are transerred for following coenzymes...

Thiamine Pyrophosphate (B1)
Flavin Adenine Dinucleotide (B2)
Nicotinamide Adenine Dinucleotide (B3)
CoEnzyme A (B5)
Lipoate
ATP
Uridine Diposphate
Thiamine Pyrophosphate - Aldehyde
Flavin Adenine Dinucleotide (B2) - electrons
Nicotinamide Adenine Dinucleotide (B3)- electrons
CoEnzyme A (B5)- Acyl group
Lipoate - Acyl group
ATP - Phosphate
Uridine Diposphate - Hexoses
What is FMN? How is different than FAD?
FMN - Flaving mononucleotide is a Riboflavin derives coenzyme -

Its strucutre is... P-P-Ribitol-Flavin
What are generic names for following vitamins?

Vitamin B1
Vitamin B2
Vitamin B3
Vitamin B5
Thiamine
Riboflavin
Niacin
Pantothenic acid
Niacin can be derived from which amino acid?
Tryptophan (but this is not an efficient way to synthesize niacin)
Acy groups are linked to CoA through a _____ bond.
Thioester (Acy groups react with SH on the pantothenic acid)
How many electrons and protons do following cofactors accept?

NAD
NADP
FAD
NAD - 2 e and 1 H
NADP - 2 e and 1 H
FAD - 2 e and 2 H
What is the significance of -- gulonolactone oxidase?
This is the enzyme necessary to synthesize escorbic acid. Higher organisms don't have this enzyme, so escorbic acid is required in the diet.
Which vitamin is synthesized by intenstinal microorganisms?
Biotin (Vitamin H or B7)
Which GLUT is found in almost all the cells?

What is the approximate Km for this GLUT?
GLUT1

approx 1mM (Which is lower than serum glucose levels so it has a constant transfer rate).
Insulin increase glucose uptake by increasing number of ______ in the plasma membrane.
GLUT4 (Exercise has the same effect)
____ and ____ are the transmembrane proteins responsible for transferring fructose into cells.
GLUT2 (into liver) and GLUT5 (intestine).
Where are following GLUTs found?

GLUT1
GLUT2
GLUT3
GLUT4
GLUT5
GLUT1 - All cells
GLUT2 - Live and Pancreas
GLUT3 - Neural cells
GLUT4 - Muscle and fat cells
GLUT5 - Intestine
List the different paths that G6P can take...
(1) conversion to glycogen (storage)
(2) hexose monophosphate shunt (production of pentoses)
(3) glycolysis (energy prod)
(4) conversion to glucose and release (only in liver, kidney and intestine)
Where are all the enzymes (for most of the metabolic pathways) are located?
In cytosol
What are the two types of fermentation?
Homolactic (glucose to lactate acid) and Alcoholic (glucose to ethanol)
Where are following GLUTs found?

GLUT1
GLUT2
GLUT3
GLUT4
GLUT5
GLUT1 - All cells
GLUT2 - Live and Pancreas
GLUT3 - Neural cells
GLUT4 - Muscle and fat cells
GLUT5 - Intestine
Homolactic fermentation

Alcoholic fermentation
glucose to lactate acid

glucose to ethanol
Phosphofructokinase is activated by....

inhibited by...
Activated by the binding of AMP and ADP at the allosteric sites.

Ihibited by binding of ATP and Citrate at the allosteric site.
List the three irreversible steps of glycolysis...
1st step - Glucose to G6p - (ATP used).

3rd step - F6P to F1,6-bisphosphate (ATP used).

10th step - Phosphoenolpyruvate to pyruvate (ATP produced)
What are the inhibition factors for 10th step of glycolysis?
ATP (If ATP is available no need to product it).

Fatty acids and acetyl-CoA (if fa are being used for energy, no need to use carbs)
Main glycolysis limiting step is...
PFK (phosphofructokinase), when F6P goes to F1,6-bisphophate.
What is the primary limiting step in fructose metabolism in liver?

In non-hepatic tissues?
In liver, not closely regulated. Fructose metabolism rate is very high in liver.

In non-hepatic tissues, hexokinase converts Frc to F6P and then PFK converts that to F16bisP. (PFK is the limiting step - just like for glucose)
List four functions of pentose phosphate pathway.
(1) Reduce G6P to Pentose sugar.
(2) Produces reducing agent NADPH - which can be used in biosynthesis processes.
(3) Provides the cell with R5P which can be used in the synthesis of nucleic acids or nucleotides.
(4)Ocassionaly, pentose to hexose.
Erythrocytes use PPP enzymes to...
generate NADPH and to reduce glutathione.
List the substrates for each step of the oxidative pentose phosphate pathway?
G6P (+ G6P-DH)

5-Phospho Glucono- delta lactone (+ Lactonase)

6-Phospho gluconate (+6PG-DH)

D-Ribulose 5P (+ phosphopentose isomerase)

D-Ribose 5P
Which steps in the oxidative pentose pathway produce NADPH?
Step 1 and Step 3

(step 4 is the isomerase step)
Compare the functions of phosphopentose isomerase and epimerase?
Isomerase - Ribulose to Ribose

Epimerase - Ribulise to Xylulose
Name the key enzymes involved in the non-oxidative branch of pentose-phosphate pathway?
Transketolase

Transaldolase
Cofactor associated with transketolase is...
TPP
What are the net products of...

oxidative PPP pathway

Both pathways working together

Non-oxidative pathway
Oxidative - NADPH and Pentose sugar

Both - NADPH

Non-oxidative - Pentose
What is glutathione?

It functions to...
Glutathione is a good reducing agent. (Erythrocytes use the NADPH produced by PPP pathway to create glutathione).
(1) Maintain sulfhydryl groups of proteins in the reduced state.
(2) Maintain the heme group of iron in the ferrous state.
(3) Eliminate ROS (such as H2O2) formed during aerobic metabolism.
Name two key elements required for glutathione synthesis
Glutathoine reductase
NADPH (produced during PPP pathway)
Describe why patients with G6P-DH deficiency are especially senstive to oxidative stress....
G6P-DH converts G6P to 5-Phosphate Glucono delta lactone. (1st step in oxidative PPP pathway).

NADPH produced during this step is used to reduce glutathione.

If reduced glutathione is not available, ROS can't be stabilized and so the patients become especially sensitive to oxidative stress.
G6P-DH deficiency is results in acute effect in...
RBC because they don't have mitochondria, so only way for them to get NADPH (energy) is through PPP.
Describe the function of Glutathione peroxidase.

GP requires _____ for its activity.
It uses reduced Glutathione to convert peroxise (ROS) alcohol.

Selenium
What is the first committed step in aerobic metabolism in the mitochondria?
PDH Reaction.
Describe steps in pyruvate dehydrogenase complex?
(1) Pyruvate is decarboxylated.
(2) Acetyl group is transferred to TPP then to Lipoic acid and then to CoA.
(3) Reoxidation of the lipoamide disulfide with E3 and FADH2 is generated.
(4) NADH is created.
What are the functions of following enzymes in pyruvate dehydrogenase complex?

E1
E2
E3
E1 - Decarboxylates Pyruvate (1st step)
E2 - Transfer of acetyle group from TPP to Lipoic acid.
E3 - Oxidation of lipoamide (to crease FADH2).
What is the function of PDH kinase?
What are the inhibiting and activating factors for PDH kinase?
PDH Kinase phosphorylates PDH complex. When phosphorylated, PDH complex is inactive.

Activating factor - ATP, NADH, acetyl-CoA

Inhibiting factor - Increase in pyruvate, ADP, NAD+, CoASH
Which two steps in glycolysis use ATP?
Glc to G6P
F6P to F1,6bisphosphate
Which step produces NADH in the cytosol? How many ATPs can be produced from this NADH?
2-glyceraldehyde 3-phosphate to 1,3bisphosphoglycerate. (produces 2 NADH)

3 to 5 depending on the shuttle used to transfer this NADH into the mitochondria.
Anaplerotic reactions
Reactions that replenish supply of oxaloacetate.
Which molecule is responsible for transferring FA into the mitochondria?
Carnitine
Carnitine
Molecule that is responsible for transferring FA into the mitochondria.
What is function of carnitine acyltransferase?
Take the FA (acyl) off of acyl-CoA and put it on carnitine.

Also knows as palmityl.
What is transporter (translocase) enzyme?
Takes acyl-carnitine complex to the inner mitochondrial membrane.
What is function of carnitine-acyltransferase II?
Takes acyl group off of carnitine and puts it back on the CoA. (so now we have acyl-CoA again).
How is beta oxidation different in mitochondria vs. peroxisome?
(1) In first step, Reduced FADH2 goes to electron chain in mitochondria. However, in peroxisome, it is broken down and peroxide is formed. (Catalase breaks peroxide into water).

(2) Reduced NADH in mito is sent to transport chain. In peroxisome it is exported out and sent to the mitochondria.

(3) Acetyl-CoA is exported out of peroxisome and into mitochondria for reoxidation but in mito it is sent to TCA cycle.
Where does glucogenesis occur?
In liver and renal cortex.
What is the daily glucose requirement of the brain in a typical adult?

Glucose in body fluids?

Glucose stored in body as glycogen?
120 grams
20 grams
190 grams
List the three steps of glycolysis that are irreversible.
(1) Hexokinase (Glucokinase) - Glc to G6P (ATP used)
(2) PFK - F6P to F1,6bisP (ATP used)
(3) PK - PEP to Pyruvate (ATP generated)
Why must oxaloacetate be transferred to malate before tranferring it back to cytoplasm (part of the gluconeogenesis pathway)?
Because oxaloacetate can't travel through membrane AND malate can.
Which enzyme is found in the ER of liver?
Glucose-6-Phosphatase. Which is converting G6P to Glc (in gluconeogenesis pathway).

Liver is where the glucose is being produced. Hence, this enzyme is needed to transfer glucose out into the blood stream.
What is the net energy (ATP) use/production during Pyruvate to PEP tranfser in

Glycolysis and
Gluconeogenesis
Glycolysis - PEP to Pyruvate produced 1 ATP (PK is used).

Gluconeogenesis - Pyruvate to PEP required 2 ATP molecules. (there are intermediate steps).
What is the function of malate dehydrogenase?
Shuttle used to tranfser oxaloacetate out of the mito. Oxaloacetate is coverted to malate and after it comes out of the mito, it is converted back into oxaloacetate (which is then converted to PEP).
What is the net energy usage/production of glycolysis and gluconeogenesis?
Glycolysis - Exergonic - +2ATP

Gluconeogenesis - Endergonic - -6ATP
What is the function of Pyruvate carboxylase?
Convert Pyruvate to Oxaloacetate (first step in gluconeogenesis). Happens in Mito.
Which substrate is required by citrate synthetase to produce citrate for TCA cycle?
Oxaloacetate (last step in TCA cycle - Oxaloacetate comes from malate)
Define anaplerotic reactions?
Reactions which can be used to replenish the supply of oxaloacetate.
Give two examples of anaplerotic reactions..
(1) Pyruvate carboxylation to create oxaloacetate (Pyruvate carboxylase is the enzyme and accumulated Acetyl-CoA has positive allosteric effect)

(2) Transamination.
glutamate to alpha-ketoglutamate
aspartate to oxaloacetate
Steps of the Gluconeogenesis pathway...
(1) Pyruvate carboxylase
(2) Malate dehydrogenase
(3) Malate dehydrogenase
(4) PEP Carboxykinase
(5) Reversible steps of glycolysis
(6) F1,6bis-phosphotase
(7) glucose-6-phosphotase
Can Acetyl-CoA enter gluconeogenesis pathway?
No, because Acetyl-CoA is a 2-C molecule. Two 3-C molecules are required to generate glc via gluconeogenesis pathway.
Which reaction supplies NADH...

(1) In the normal gluconeogenesis pathway
(2) In the alternate gluconeogenesis (lactate) pathway
(1) Malate shuttle

(2) Lactate dehydrogenase reaction (lactate goes to pyruvate)
Cytosolic PEPCK vs. Mito PEPCK.
Cytosolic PEPCK - Used when AA or TCA intermediates are used to produce glucose and malate shuttle generates NADH.

Mito PEPCK - Used when lactate is used for gluconeogenesis and lactate dehydrogenase generates NADH.
Which steps in gluconeogenesis use ATP?
(1) Pyruvate Carboxylase
(2) PEPCK
(3) Phosphoglycerate kinase
What is released in the blood stream for....(1) cori cycle and (2) alanine cycle
(1) Lactate (Muscles release lactate which is picked up in liver and then converted to glucose).

(2) Alanine (which is converted to pyruvate and urea acid in liver)
Which amino acids can't enter gluconeogenesis pathway?
Leucine and Lysine -- Because they break down to 2C products and ONLY 3C molecules can enter gluconeogenesis.
Even numbered FA yield...

Odd numbered FA yield...
Acetyl-CoA (which can not enter gluconeogenesis pathway)

Propionyl-CoA (which can enter gluconeogenesis)
Where does glycerol enter glycolysis or gluconeogenesis pathway?
Glycerol is converted to DHAP. As DHAP, it can enter glycolysis or gluconeogenesis pathway.
What controls glycolysis/gluconeogenesis in liver vs. in muscle?

(what drives these pathways)
In Liver - Blood glucose levels

In Muscles - Energy balance. Metabolic need.
F2,6bis-phosphate activates...

Inhibits..
It activates..PFK so Glycolysis progresses.

It inhibites F1,6Bisphosphotase, so gluconeogenesis is inhibited.
Compare the structures and functions of

PFK2 and Fructose 2,6 bisphosphatase
PFK2 - Produce F2,6bisphosphate. Dephosphorylated.

Fructose 2,6 bisphosphatase -Produce F6P. Phosphorylated
Explain how High Insulin in blood regulate glycolysis.
High Insulin --> Dephosphorylation of bifunction enzyme (PFK2) --> Generation of F2,6bisphosphate. --> Activate PFK (and inhibit F16Bphosphatase) --> F1,6Bisphophate is produced and commited to glycolysis.
How does Glucagon regulate gluconeogenesis pathway?
Glucagon phosphorylates bifunctional enzyme. Hence, F2,6BP is brought back to F6P. So PFK is not activated and F1,6bisphophatase is not inhibited. Hence, F6P is produced and gluconeogenesis is supported.
List four enzymes that regulate gluconeogenesis?

Which enzyme regulates gluconeogensis vs. glycolysis.
(1) Pyruvate carboxylase
(2) PEPCK
(3) F1,6bisphosphatase (regulated by F2,6bisphosphate)
(4) G6Ptase

F2,6BP (bifunctional enzyme and hormones are involved)
How does function of glycogen change in liver versus in muscle?
In liver - Glycogen is generated back to glucose and released back into blood.

In muscles - Glycogen is broken back to be used for energy.
List the four enzymes involved in degradationof glycogen?
(1) Glycogen Phosphorylase (break side chains upto 4 residues from a branch).
(2) Glycosyl Transferase (cleaves from 4th residue to the beginning.
(3) alpha(1->6)glucosidase (removes single residue)
(4) Phosphoglucomutase (G1P to G6P)
Which enzyme is most important in glycogen degradation?
Glycogen phosphorylase
What is the end product of glycogen degradation?
G6P
Where is G6Ptase generated?
In cytosol of liver.
What is the function of glycogen synthetase?
Take glucose from UDP-Glc complex and add it to the non-reducing end of the glycogen.
What is used to convert G6P to G1P?

G6P to F6P

G6P to Glc
Phosphoglucomutase (glycogen synthesis)

Phosphoglucose Isomerase(glycolysis)

G6Ptase
During glycogen synthesis, which enzyme forms alpha(1->6) bonds?
Branching enzyme.
List the three enzymes involved in Glycogen synthesis?
(1) UDP-Glc Pyrophosphorylase (add Glc to UDP)
(2) Glycogen Synthetase (take glc from UDP-glc and add it to non-reducing ends of Glycogen)
(3) Branching enzyme - create alpha(1->6) links and add branches to glycogen structures.
Which protein serves as primer for glycogen synthesis?

How does it work?
Glycogenin (It remains in the core of the glycogen molecule).

It catalyzes the transfer of a glc residue from a UDP-glc molecule to the OH group of tyrosine.
How does following effect gluconeogenesis and glycogen synthesis?

Insulin
Glucagon
Epinephrine
Insulin - Inhibits gluconeogenesis. Activates Glycogen Synthesis.

Glucagon - Activates gluconeogenesis and activates glycogen breakdown in liver.

Epi - Activates glycogen breakdown in muscle. Inhibits gluconeogenesis.
cAMP is produced from _____ in response to rising _____.


What happens to cAMP in response to high insulin levels?
ATP, Glucagon (because cAMP promotes Glycogen degradation).

cAMP breaks down (so no more inhibition of glycogen synthesis).
Dephorphorylation/Phosphorylation

Glycogen synthetase is inactivated by ______.

Glycogen phosphorylase is inactivated by ______.
Phosphorylation (cAMP)

Dephosphorylation
What is the effect of cAMP on glycogen synthetase and glycogen phosphorylate.
It phosphorylates them both (via intermiediary enzymes).

However, phosphorylation ACTIVATES phosphorylase (glycogen degradation) and INACTIVATES synthetase (glycogen synthesis). Hence, cAMP is resulting in Glycogen breakdown. Which makes sense because cAMP is release in response to Glucagon.
How does activated glycogen phosphorylase impact glycogen synthetase?
It prevents glycogen synthetase from dephosphorylating (becoming active) by BLOCKING protein phosphatase.
Understand cascade effect..
It is good because the response has higher magnitude.
List three differences in the glycogen metabolism pathways in liver versus muscle.
(1) In liver, Glucagon activates glycogen degradation -- In muscles, epi activates glycogen degradation.

(2) In muscles, AMP directly activates Glycogen Phosphorylase (so glycogen degradation happens because AMP means no ATP).

(3) In muscles, Ca2+ can activate Phosphorylase Kinase A which can phosphorylate Glycogen Phosphorylase so that glycogen can be degraded.
List two enzymes which when defected would effect only liver.
(1) Glc-6-ptase
(2) Microsomal P Transporter (transport glc out to blood stream in liver).
Which pancreatic cells produce..

Insulin?
Glucagon?
Pancreatic Polypeptide?
Somatostatin
Insulin - B cells
Glucagon - A cells
Pancreatic polypeptide - F cells
Somatostatin - D cells
What is unique about insulin structure among different vertebrates?
The structure is mostly similar. Hence, in treatment insulin from one mammal can be used in another mammal.
List two rapid-acting and two long-acting designer insulins?
Rapid Acting - Insulin Lispro, Insulin Aspart

Long Active - Insulin Glargine, Insulin Detemir
Describe the changes for following designer insulin.

Insulin aspart
Insulin lispro
Insulin glargine
Insulin Detemir
Insulin aspart - B28 Proline to Asp

Insulin Lispro - Switch B28Pro and B29Lys

Insulin Glargine - Add 2 Arg at the end of B chain

Insulin Detemir - Acylation of amino group of Lys B29
Which designer insulin binds closely to insulin?
Insulin Detemir (acylation of amino group of Lys B29)
Where is preproinsulin synthesized?
Preproinsulin is synthesized in ER of b cells of islet of langerhans.
What is the usage of C peptide (that was produced during insulin production)?

Decreased C-Peptide are indicators for....
C-peptide has limited biological activity but it is mainly used for diagnostic purposes.

It is a good indicator of how much insulin a person is producing (esp when patient is under insulin treatment).

Decreased C-peptide are an indicator of Type I diabetes.
How does epinephrine impact insulin release?
Inhibits it.
List 4 effects that insulin has on muscle cells..
(1) Uptake of glucose
(2) Uptake of amino acids
(3) glycogen synthesis
(4) protein synthesis
Which glucose transporter is insulin dependent? Where is it located?

Which enzymes are activated by insulin in muscle cells?
GLUT4. Muscles and adipose tissue.

Hexokinase
Glycogen Synthase
How does insulin impact cAMP?
Insulin degrades cAMP.
What is the significance of IRS1?
IRS1 is Insulin Receptor Substrate 1, which when activated by phosphorylation initiates a signaling cascade and various enzymes are activated which mediate insulin's activity.
What is proglucagon?
Precursor to Glucagon in Pancreas. (coverted via convertase 2)

In intestine, proglucagon gives rise to GLP1 (via convertase 1)
What is GLP1?

What is its function?
GLP1 (glucagon like protein) is produced when convertase 1 converts glucagon to GLP1 in intestine.

It enhances the release of insulin and lowers blood glucose.
Exenatide
GLP1 agonist. Lowers Blood glucose. Recently approved for Type II diabetes treatment.
What is adenylate kinase reaction?
2ADP ---> ATP + AMP

(Hence, when energy consumption is high; ADP is used and AMP accumulates. So AMP is a major control of PFK (glycolysis)
How is FA stored? (for energy usage...and membrane component...
For energy usage...as Triacylglycerols in adipose tissues.

Phospholipids - as part of membranes.
Triacylglycerol is hydrolyzed by...

It yields...
Hormone sensitive lipase...

3 X FAs and Glycerol.
Lipase is stimulated by...
cAMP
What is carnitine?
Carnitine is a special carrier moleculre, which helps get Acyl-CoA into the mitochondria (this is imp in FA metabolism, in which FA is transferred to Acyl-CoA in cytosol)
Which kind of double bond is formed by Acyl-CoA Dehydrogenase?

What is used (FAD or NAD)?
Trans Delta 2 double bond.

FAD (we are talking about first step in the beta oxidation of saturated FA)
What is the function of Enoyl-CoA isomerase?
It converts cis-delta 3 double bond to trans-delta 2 double bond.

Trans delta 2 double bond is required for oxidation of long FA chains to Acyl-CoA and Acetyl-CoA for FA metabolism.
Describe the oxidation steps for unsaturated FA chains (odd and even numbered double bonds).
Odd numbered - cis delta 3 must be converted to trans-delta 2 double bond using Enoyl-CoA Isomerase.

Even Numbered (cis d4) - First dehydrogenase step as usual so now we have (cis d4 and trans d2). Then, 2,4 DiEnoyl-CoA reductase is used to convert these two double bonds into cis d3. Then, Enoyl-CoA Isomerase is used to convert cis-d3 to trans-d2 double bond.

(Remember, trans-d2 is necessary to oxidise FA chains).
Propionyl-CoA

Its fate...
When FA has odd numbered carbons, last beta-oxidation release two carbon Acetyl-CoA and one carbon Propinoyl CoA.

Propinoyl CoA is converted to Succinyl-CoA which enters TCA cycle for further oxidation.
List 4 differences between peoxisomal versus mitochondrial beta-oxidation of FAs.
(1) Peroxisomal converts VL FA chains to smaller chains for oxidation in mitochondria.

(2) FADH and NADH produced in first dehydrogenase step is converted to H2O2 in peroxisomes (in mito, it is transferred to electron chain).

(3) NADH produced in third step can't be oxidized in peroxisomes. Reduced form is transferred to mito.

(4) Acetyl-CoA from the last step has to be transferred to Mito for TCA cycle oxidation.
What is the trifucntional enzyme?
Enzyme for the 2,3,4 steps of beta oxidation of saturated FAs.

(2) Enoyl-CoA Hydratase
(3) 3-Hydorxyacyl CoA dehydrogenase
(4) Beta-Ketothiolase
Malonyl-CoA
It is a intermediate that is released during FA synthesis.

It inhibits FA oxidation by inhibiting Carnitine Palmitoyltransferase.
What are ketone bodies?

They are formed in...
Transport form of Acetyl-CoA. (fat degraded in liver can be used as energy source in other tissues)

Formed in Liver.
Ketone bodies are formed from..when...
Acetyl-CoA when oxaloacetate levels are low and so Acetyl-CoA can not enter TCA cycle. (starvation and diabetes can cause shortage of oxaloacetate).
List the enzymes required for utilization of ketone bodies..
(1) Hydroxybuterate DHD
(2) B-Ketoacyl CoA (only found in liver - forms acetoacetyl CoA
(3) Thiolase (splits acetoacetyl CoA into two Acetyl-CoA molecules).
Which enzyme of the Ketone Body utilization pathway is now available in liver?
Beta-Ketoacyl CoA transferase
Primary site of ketone body formation is...

Utilization is..
Liver

Heart, Skeletal muscles and brain (only in extreme need).
List the two types of ketone bodies..
(1) Beta-Hydroxybuterate

(2) Acetoacetate (which is decarboxylated to produce Acetone)
How is Glycerol utilized?
(1) Glycerol is phosphorylated (using glycerol kinase).

(2) Glycerol 3-Phosphate is dehydrogenated to produce DHAP.

(3) DHAP is then converted to Glyceraldehyde 3-phosphate (using triose phosphate isomerase)
How is glycogen synthesis regulated?
Under hormonal control.

Insulin - Activate Glycogen Synthetase.

Glucagon - Activate Glycogen Phosphorylase
How is glycolysis versus gluconeogensis regulated (in liver)?
Hormonal control.

Insulin - Dephosphorylated bifunctional enzyme - PFK2 activity - F2,6BP activated - PFK activated - F1,6BPtase inhibited - Glycolysis promoted.

Glucagon -> Phosphorylate bifunctional enzyme -> F2,6BP inhibited -> PFK inhibited -> F1,6BPtase activated -> Gluconeogenesis promoted
How is ketone body formation regulated?
When Acetyl CoA Increses; Oxaloacetate decreases

Meaning..when FA oxidation is high and carbohydrate metabolism is low; Ketone bodies are formed. (starvation and diabetes are examples)
How is FA oxidation regulated?
Regulation of FA release from adipose tissues by hormone sensitive lipase plays key role.

Another method is via malnoyl-CoA (intermediate in FA synthesis). When Malnoyl-CoA is high, FA synthesis is high, so FA oxidation needs to be inhibited. It does this by inhibiting carnitine acyltransferase.
Regulation of TCA cycle...

Activators

Inhibitors
Activators - AMP, NAD+, Ca2+

Inhibitors - Succinyl-CoA, Citrate, ATP, NADH, Acetyl-CoA fatty acids
PDH Complex regulation...
ATP -> Activate Kinase -> Phosphorylated PDH complex -> Inhibits PDH complex (b/c ATP is high)

No ATP -> No Kinase -> PDH is dephophorylated -> PDH is activate (so ATP can be generated)
Regulation of PPP...
By NADP/NADPH and pentose-phosphates.
Allosteric regulation of PFK..
ATP and Citrate binding to allosteric site inhibit PFK (and glycolysis).

AMP and ADP activate it.
Describe the steps in regulation of glycogen synthesis and degradation..
Degradation => Glucagon release -> Activates cAMP -> Activates Protein Kinase A (PKA) -> Phosphorylates glycogen synthetase and phophorylase -> Glycogen Breakdown

Insuling -> Breakdown cAMP -> cAMP kinases become inactive -> Dephosphorylation ->Activate Glycogen synthetase and inhibit phophorylase -> Glycogen synthesis
What is the function of protein phosphatase (PP1)?

PP1 is inhibited by...

PP1 is activated by...
It dephosphorylates glycogen synthetase and glycogen phosphorylase.

Activate Phosphorylase. Phosphorylase A inhibits PP1 (so that synthetase can't be dephosphorylate and activated).

Glucose. Hence, Synthetase and Phophorylase are dephosphorylated and glycogen synthesis can happen.
How does Ca and AMP impact glycogen synthesis/degradation?
Both cause glycogen breakdown.

Ca activates Phosphorylase Kinase (so phosphorylase is activated).

AMP directly phosphorylates Glycogen Phsophorylase, so glycogen breakdown progresses.
Describe insulin receptor..


Describe Glucagon receptor....
two alpha and two bets subunits. Beta subunits are transmembrane. Tyrosine Kinase receptor. Insulin binding domain on alpha subunits. Binding of insulin causes autophosphorylation of tyrosine on the beta subunit which in turn phosphorylated other intracellular proteins.

Glucagon receptor works primarily on liver via cAMP. (muscle and adipose tissues are not effected by glucagon release).
Which two amino acids can not be deaminated to be used in gluconeogenesis?
Leucine and Lysine
List four main precursors for gluconeogenesis.
Alanine (deaminated amino acids - all but leucine/lysine)

Lactate (Cori cycle)

Glycerol (DHAP, Glyceraldehyde 3P)

Amino acids (Glutamate, Aspartate entering TCA cycle)
How is fructose absorption different than glucose absorption (in intestine)?
Glc absorption is via Na/Glc cotransport.

Frc absorption is via GLUT5 in the lower GI.
Ketone bodies go up during starvation because....
During starvation, blood glucose is low. Hence, oxaloacetate is being used for gluconeogensis. Hence, Actyl-CoA accumulates and ketone bodies are formed.
Leptin
Hormone signaling high fat reserves. It acts on receptors in the hypothalamus to reduce appetite. It causes higher caloric usage and thermogenesis.
What is the function of brown fat?
Brown fat changes mitochondrial membrane permeability so that protons leak out and heat is produced.

Leaking of protons dissipates the gradient for ATP generation.
What is MODY? What causes it?
Mature Onset type Diabetes of Young (type of NIDDM).

Defect in Glucokinase usually causes this type.
Explain how hyperglycemia can cause hyperlipoproteinemia and ketosis?
Glc can not enter cell so energy is not produced. Hence, FA are used (lipolysis, hydrolysis of triglycerols etc..) and so lipid goes up. Since, lipids are used for energy and oxaloacetate is not available, ketone bodies will be produced.

(Even through this is high BG, cells react as if it is low BG to get engergy - because glc is not absorbed into the cells).
What is Porin?
Protein found in the outer mitochondrial membrane. Makes channels for particle transport.
Which two enzymes are located in the intermembrane space?
Adenylyl cyclase
Creatine kinase
Describe rotary motor to form ATP (complex V in mito).
Located in the inner mito membrane.

F1 and F0. F0 rotates as protons pass through it. Rotation of F0 causes F1 to produce ATP.
List three reactions where TPP is a cofactor..
(1) PDH E1 reaction (acetyl group transfer from CoA to TPP).

(2) alpha-ketoglyterate reaction in TCA cycle

(3) Tranketolase reactions in non-oxidative PPP pathway
What is the structure of...

FAD
FMN
Coenzyme A
UDP-Glc
FAD - Adenine-Ribose-P-P-Ribitol-Flavin

FMN - P-P-Ribitol-Flavin

Coenzyme A - Adenine-RiboseP-P-P-Pantathiene

UDP-Glc - Uracil-Ribose-P-P-Glc
How is the usage of NADH different than NADPH?
NADH is primarily used as electron carrier into the electron transport chain.

NADPH is used as reducing agent in bio-synthetic rxns (FA, Cholesterol synthesis).
Which enzymes are primarily controlled by intrinsic factors?
PFK (allosteric control)

PDH (Energy charge - ATP, AMP, Citrate, ADP etc..)
Explain why defect in FA oxidation enzyme leads to hypoglycemia..
Since FA can't be used for energy, glucose is being used to glucose levels drop.