MT1 Material Flashcards

Question

Answer 1

Phosphatidylglycerol (head-group substituent of cardiolipins)

Answer 2

Oleic acid ceramide and Oleate ceramide (both accepted as correct answers) This molecule is a.... **sphingolipid**!

Answer 3

C26:0 sphingomyelin

Answer 4

Glucose Glucosyl**cerebroside**

Answer 5

A cerebroside

Answer 6

A sphingolipid with a head-group substituent that is a complex oligosaccharide.

Answer 7

Chain length: more carbons \> higher melting T due to more van der Waals interactions Number of double bonds: more double bonds \> lower melting T (cis double bonds introduce kinks in FA tails disrupting van der Waal's interactions)

Answer 8

Malonyl-CoA

Answer 9

Phosphatidyl inositol

Answer 10

Stearate (C18:0) esterified to wax: long chained alcohol (C18:1 Δ⁹)

Answer 11

Trans oleic acid (C18:1 trans Δ⁹)

Answer 12

Linoleoyl carnitine

Answer 13

Bile salt: taurocholic acid

Answer 14

p-hydroxyphenylpyruvic acid (phenylalanine would only receive partial marks - see structure of phenylalanine below)

Answer 15

farnesyl pyrophosphate

Answer 16

ceramide esterified with an oleate derived acyl chain

Answer 17

Phosphatidylinositol esterified with stearate and arachidonate dervied acyl chains

Answer 18

ß-ketostearoyl-CoA

Answer 19

Phosphatidylinositol with palmitate and arachidonate derived acyl chains

Answer 20

alpha-ketoacid of isoleucine or 2-keto-3-methylpentanoate or alpha-keto-ß-methylpentanoate

Answer 21

acetyl-CoA or acetoacetyl-CoA

Answer 22

Acetoacetyl-CoA

Answer 23

Acetyl-CoA

Answer 24

Phosphatidylethanolamine esterified with two stearic acids (C18:0).

Answer 25

Sphingomyelin with an amide linkage to palmitic acid (C16:0)

Answer 26

**pyruvate** or **TCA cycle intermediates**

Answer 27

**b.** Oxidative deamination is the conversion of an amino acid to a keto acid plus ammonia.

Answer 28

**f.** A, B and C

Answer 29

**In tissues of the liver.**

Answer 30

**e****.**Very low carbohydrate,**very high protein**

Answer 31

Glutamine synthetase converts **glutamate** to **glutamine** whereas glutamate dehydrogenase converts **glutamate** to **alpha-ketoglutarate.**

Answer 32

**Dopamine** is an intermediate in the conversion of **tyrosine** to **epinephrine**.

Answer 33

False | (True in fatty acid synthesis)

Answer 34

**NADPH** is produced in the **cytosol** by **malic enzyme**. ## Footnote *Note: NADPH is also produced by pentose phosphate pathway.*

Answer 35

False. Oxaloacetate + acetyl-CoA \> citrate

Answer 36

True. There are two separate pools of coenzyme A.

Answer 37

Malonyl-CoA is formed in the **cytosol** by **acetyl-CoA carboxylase (ACC)**.

Answer 38

False, carbon returns via **malate** or **pyruvate**.

Answer 39

**acetyl-CoA**

Answer 40

**malonyl-CoA**

Answer 41

During starvation the body lacks fuel sources and needs to break down its non-essential protein reserves into amino acids. Skeletal cells contain the vast majority of the body's protein reserves. The ubiquitin-proteasome system breaks down the intercellular proteins. The 20 amino acids released from muscle then serve as precursors to make glucose (gluconeogenesis by liver), make ketone bodies (also liver) _OR_ their carbon skeletons are oxidized directly. Oxidation of these fuels produces reducing agents (e.g. NADH) driving the ETC, generating an electrochemical gradient, thus allowing ATP synthase to make ATP.

Answer 42

The ubiquitin-proteasome system is specific! ## Footnote Ubiquitination is targeted at a much higher rate at sarcomeric proteins. The cell will contain specific E3s that will preferentially target sarcomeric protein over other house-keeping proteins. Other proteins such as metabolic proteins/enzymes that the cell needs to survive will be maintained (i.e. the rate of degradation will equal rate of synthesis).

Answer 43

Proteins involved in protein degradation, such as ubiquitin, E1 (Ub activating enzyme), E2 (UB conjugating enzyme) and the specific E3 (Ub ligase) required to target each of the sarcomeric proteins, as well as the subunits (e.g. alpha and ß) required to synthesize the 26S proteasome. In the liver cell the urea cycle enzymes will be upregulated in order to dispose of the nitrogenous waste.

Answer 44

oxaloacetate

Answer 45

Phenylalanine

Answer 46

Alpha-ketoglutarate

Answer 47

α-ketoglutarate

Answer 48

α-ketoglutarate

Answer 49

Hydroxyphenylpyruvate

Answer 50

4-Hydroxyphenylpyruvate

Answer 51

Pyruvate and glutamate

Answer 52

Hydroxyphenylpyruvate and glutamate

Answer 53

Leucine and alpha-ketoglutarate

Answer 54

Oxaloacetate and glutamate

Answer 55

Hydroxyphenylpyruvate and glutamate

Answer 56

Leucine is a strictly ketogenic amino acid. As such, its carbon skeleton (alpha-ketoisocaproate) produced by branched chain aminotransferase will be broken down into acetyl-CoA, and then completely oxidized (on site) to CO₂ + H₂O by the TCA cycle. Note: The muscle cell cannot synthesize ketone bodies!

Answer 57

Alpha-ketoglutarate is produced by Alanine aminotransferase for every N atom moved from Glutamate to Alanine (subsequentely exported from muscle to liver). This alpha-ketoglutarate is simply cycling with other 'upstream' aminotransferases (e.g., TAT, branched chain aminotransferase, AST, etc.) that all require alpha-ketoglutarate as substrate. Alpha-ketoglutarate is a transport mechanism for N from upstream amino acids to the N-acceptor, pyruvate. As the N is 1:1, there is no net change in alpha-ketoglutarate level. No depletion. No accumulation.

Answer 58

In a working muscle, the alpha-amino group nitrogen is moved from the respective amino acid (breakdown pathways) to primarily pyruvate, forming alanine. Alanine leaves the muscle cell (alanine transporter), enters the blood and is imported by the liver (alanine transporter). The liver further metabolises the nitrogen in Alanine to eventually produce urea. To a lesser extent, some of the nitrogen will also be used to make Glutamine (Glu + NH₄⁺ \> Gln). Glutamine is transported to the liver to help move the N and produce urea.

Answer 59

Albumin is a protein that binds fatty acids in the blood (a fatty acid carrier protein). Its function is to transport fatty acids from adipose tissue to the cells that need them (e.g., muscle cell). This occurs during fasting _or_ starvation.

Answer 60

Fatty acids are \>1000x more likely to be bound to albumin than exist free in blood! Fatty acids are primarily hydrophobic (long hydrocarbon tail) and have minimal hydrophilic character (carboxylic head group). As such they have _low stability_ in aqueous environments such as blood. This is observed experimentally by the low concentration of free FA in blood (note: nM range). In order to mobilize large amounts of FA from adipose tissue to cells that need them, a transporter protein such as albumin is required. The majority of FA in blood are thus bound to albumin, effectively raising the stability up to ~30,000 fold!

Answer 61

After eating (times of plenty, fed part of fed-fast cycle, insulin-signaling), most cells in the body use glucose as a fuel source. Fatty acids coming from the intestinal tract will be esterified to glycerol and carried as triacylglycerols in chylomicrons. FAs are not picked up by albumin from the intestine. Thus, most albumin molecules will have little FA bound to them (0-2 FA per albumin, corresponding to the lower 50uM range). However, upon fasting, glucagon-signalling causes the mobilization of fat stores in adipocytes. FAs signalling causes the mobilization of fat stores in adipocytes. FAS are released into the blood where they are bound by albumin. Now the albumin molecules become heavily loaded: ~6-7 FA per albumin!

Answer 62

Pyridoxal phosphate

Answer 63

The biological activity of insulin would be destroyed by the low pH of the gastric juices in the stomach as well as by the proteases (e.g., pepsin, chymotrypsin, etc.) that act in the stomach and small intestines. Even if insulin escaped degradation and refolded to its active state, it would NOT enter the blood from the intestine. The transporters that line the intestinal lumen transport free amino acids, NOT intact proteins.

Answer 64

The hydrocarbon chain would form the hydrophilic core and span the membrane (analagous to 2x acyl chains of e.g., eukaryotic membranes). The free hydroxyl groups (or polar derivatives) on either side would form polar 'head groups' analogous to polar heads of 2x leaflets of eukaryotic membranes.

Answer 65

1. Archaea lipids have glycerol linked to hydrocarbon chains by **ether** linkages. Glycerophospholipids have glycerol linked to hydrocarbon chains by **ester** linkages. 2. The hydrocarbon chains of archaea lipids (C32) are 2x as long as that of glycerophospholipids (C16-20) 3. The hydrocarbon chain of archaea lipid is branched with methyl groups (fully saturated isoprenoid units), whereas, hydrocarbon chains of phospholipids are NOT branched (e.g., palmitate).

Answer 66

**Thermal**: The archaea compound is stable at high temperatures because of the many van der waals interactions down the carbon chain. There is also limited mobility as there is _no bilayer_ in this membrane as the 'leaflets' are covalently linked. The methyl groups would prevent further rotational mobility and increase van der waals interactions. All these factors increase T_M of membranes. **Chemical**: The ether linkages are stable to chemical hydrolysis. For example at pH 10, ester linkage would hydrolyze with OH nucelophilic attack. Lipases cannot hydrolyze.

Answer 67

Both ketogenic amino acids and even-numbered carbon FAs will _only_ produce acetyl-CoA, which can be directly oxidized by the TCA cycle and oxidative phosphorylation to produce ATP, _OR_ it can be used to make ketone bodies in the liver and then exported (e.g., to the brain) again for ATP production.

Answer 68

Both glucogenic amino acids and odd-numbered carbon FAs can lead to the generation of acetyl-CoA _AND_ TCA cycle intermediates that can subsequently be used as precursors to build glucose (gluconeogenesis). Thus, they can both be used as a carbon source to fuel the brain by generating _glucose_.

Answer 69

Muscle tissue will waste away. The body has no direct supply of glucose, so will need to make glucose. Once glycogen stores run out (~24hrs), gluconeogenesis will have to supply blood glucose. Neither strictly ketogenic amino acids, nor even-numbered carbon FAs can be used as a carbon source in gluconeogenesis. The body will thus break down muscle tissue (primarily skeletal muscles) as a source of gluconeogenic amino acids. These can be converted to glucose to continue to supply the brain with its required fuel source.

Answer 70

1. Condensation 2. Reduction 3. Dehydration 4. Reduction

Answer 71

The synthesis of palmitate requires 7 rounds of synthesis, including seven dehydration reactions (ß-hydroxyACP dehydratase). After the last round of synthesis, the 16-carbon acyl chain is still attached by thioester linkage to ACP. Thioesterase uses 1 H₂O (as substrate) to hydrolyze palmitoyl-ACP to release palmitate. (7-1 = 6)

Answer 72

When fish release ammonia into the surrounding aqueous environment, it is diluted to non-toxic levels. The ammonia produced (e.g., by amino acid catabolism) in mammals _cannot_ be sufficiently diluted in the tissues and blood to avoid accumulating toxic amounts. Urea is much less toxic than ammonia. Ammonia is also highly toxic to fish, but its dilution into the aquatic environment results in concentrations that are less than toxic.

Answer 73

Cholesterol's steroid nucleus prevents close packing of long-chain fatty acids in adjacent lipids, increasing membrane fluidity at low temperatures.

Answer 74

**g. Two of the above**

Answer 75

The degradation of arachidonate (C20:4 all cis Δ^5,8,11,14) in the mitochondrial matrix requires **9** rounds of breakdown and produces **10** molecules of acetyl-CoA.

Answer 76

Inability to regenerate tetrahydrobiopterin (THB) from dihydrobiopterin

Answer 77

1. Oxidation 2. Hydration 3. Oxidation 4. Thiolysis

Answer 78

Note: No cofactor necessary for this enzyme. Glutamate dehydrogenase performs **oxidative deamination.**

Answer 79

This is a redox reaction. The carbon substrate (Glu) is oxidized as there is a loss of electrons going to the product (alpha-KG). Both H₂O and NH₄⁺have four e^- pairs and are not involved in the redox reaction. (i.e., the first step in the reaction with NAD(P)⁺ to form the reaction intermediate is a redox reaction).

Answer 80

Glucagon signals adipocytes and via the cAMP-dependent signal transduction cascade activates protein kinase A (pkA). PKA phosphorylates hormone sensitive lipase (and long with CPI) allows TAG molecules to be broken down into fatty acids and glycerol. These are then released into the blood. Tissues that catabolize FAs will bring them into the cytosol, link them to CoASH and via the carnitine shuttle move them into the mitochondrial matrix, to perform oxidation. For cells that have acetyl-CoA carboxylase (ACC), glucagon also ensures that ACC is phosphorylated and inactive. This ensures that CATI and the carnitine shuttle are working.

Answer 81

Both reactions are performed by thiolases (aka acyl-CoA acetyl transferase). ß-oxidation uses coenzyme A to cleave acetoacetyl-CoA into 2x acetyl-CoA. Thiolase of ß-oxidation operates in the mitochondrial matrix of ALL cells except the brain (e.g., epithelial cells). In cholesterol synthesis, this reaction operates in 'reverse': i.e., two acetyl-CoA combine to form acetoacetyl-CoA with the release of CoASH. Thiolase of cholesterol synthesis operates in the cytoplasm the cells of the liver (or intestine).

Answer 82

* Transcriptional regulation of the gene that expresses the rate-limiting enzyme thereby changing [E]. * Translational regulation of the mRNA that expresses the rate-limiting enzyme thereby changing [E]. * Reversible phosphorylation of the rate-limiting enzyme. Phosphorylation could increase or decrease the enzyme activity. * Control the enzyme degradation rate by changing the half-life (Ub-dependent degradation) * Allosteric activators or inhibitors of the rate limiting enzyme will increase or decrease the enzyme activity, respectively.

Answer 83

* Proteins removed by the Ub-dependent pathway have to be at minimum tetra-ubiquitinated. Attachment of 1 (one) Ub (by E1, E2, E3) costs the equivalent of 2 ATP. Thus at least 8 ATP are required. * Once ubiquitinated, the target protein is degraded by the 26S proteasome. Unfolding the target protein by the 19S cap, as well as threading the protein into the core are energy costing _or_ ATP-dependent processes. Presumably the longer the polypeptide the higher the ATP cost (a stoichiometric equivalent here is unknown). * Other energy considerations are the cost of protein synthesis of the protein degradation machinery, (i.e., E1, E2, E3 suite of enzymes, Ub, 26S proteasome, and the suite of cellular peptidases).

Answer 84

The ß-ketoacyl reductase reaction in both mammals and bacteria occurs in the cytosol. The mammalian KR domain is part of FAS. The carbon substrate and product are attached to ACP, another domain of FAS. Thus the carbon produt of KR (pathway intermediate) remains tethered to FAS and rapidly diffuses to the subsequent active site (i.e., DH domain of FAS). In the KR reaction catalyzed in bacteria, the reaction is performed by the KR enzyme, a free enzyme. The carbon product of KR (pathway intermediate) diffuses into the cytoplasm and has to diffuse into the active site of the free DH enzyme. This is not as efficient as the mammalian catalyzed reaction. Tethering the pathway intermediates and having all enzymes joined as domains is much more efficient to 'flux' a metabolite through a pathway.

Answer 85

Ubiquitin activating enzyme (UbA), conjugating enzyme**s** (UbC), and ligase**s** (UbL). Also 26S proteasome and cellular peptidase**s**.

Answer 86

The biosynthetic pathway depends on both Lysine and Methionine which are both essential amino acids! These must be supplied from the diet.

Answer 87

These patients do NOT have argininosuccinase activity and thus their urea cycle does NOT turn. They cannot form urea and do NOT have the ability to eliminate excess nitrogen. Arginine allows them to regenerate ornithine allowing for N incorporation from peripheral amino acid catabolism. The ornithine incorporates NH₄⁺ and Aspartate to synthesize argininosuccinate, which is secreted and excreted by the kidney. This proess however also uses up oxaloacetate (OAA) in the matrix for every argininosuccinate excreted. To prevent this loss of OAA, the diet is supplemented with OAA.

Answer 88

A peripheral cell (e.g., epithelial cell) does not have the enzymes (ACC, FAS) to make fatty acids, and as such cannot perform such a futile cycle. Only the liver, adipocytes, and mammary gland cells perform FA synthesis. In a liver cell, ACC is either phosphorylated (inactive) or dephosphorylated (active). This reversible phosphorylation is controlled by hormones (glucagon phoshorylates, insulin dephosphorylates), or other cellular mediators (e.g., AMP dependent kinase). When ACC is active, its product malonyl-CoA is made resulting in increased [malonyl-CoA]. This results in FA synthesis (substrate for FAs) and negative allosteric regulation of CATI, preventing fatty acyl transport into the matrix, thereby depriving the ß-oxidation enzymes of their substrates. When ACC is inactive, there is no malonyl-CoA and therefore no substrate for FA synthesis. In this case there is no inhibition of CATI and FAs are transported by the carnitine shuttle into the matrix for oxidation.

Answer 89

Final answer (either accepted) Costs 27 ATP Costs 36 ATP

Answer 90

1. FA are almost completely reduced (little oxygen) \> can harvest more energy per gram (38kJ/g) for FAs vs 17kJ/g for carbs) 2. TAG are hydrophobic and don't need water to store compared to glycogen. Thus, we can pack more TAG in a given volume.

Answer 91

**1. Fatty acids (FA)** - carboxylic acids containing long hydrocarbon chains that can be saturated or unsaturated. **2. Triacylglycerols** - glycerol that has FA esterified to each of the OH groups. **3. Glycerophospholipids** - composed of a glycerol backbone to which 2 FAs are attached, but carbon #3 is linked by a phosphodiester bond to phosphate, which in turn is linked to a head group (alcohol) **4. Sphingolipids** - have sphingosine as a base that consist of a polar head group attached by -OH, and also have a free -OH group and one FA chain attached by amide linkage **5. Steroids** - lipids containing core of 4 fused rings (A-D): A-C 6C, D 5C. Steroid + alcohol = sterol. Planar, rigid and sterols are amphipathic. See figure. **6.** **Waxes** - esters of FA linked to long chain alcohols - highly hydrophobic and non-polar (e.g., plant leaves) **7. Eicosanoid** - signaling molecules involved in the inflammatory response.

Answer 92

* Sheet like structures composed of lipids and proteins and usually 2 bilayers. * Form closed boundaries between cells and compartments within cells. * 3 major lipid components: glycerophospholipids, sphingolipids, and sterols (in animals cholesterol, plants use other sterols as well) Note: Bacteria do not have biosynthetic pathways for sterol, but may incorporate some exogenous sterols into their membranes. * Basic structure: bilayer (inner and outer leaflets) and small polar (glucose) or charged (ions) molecules. * Permeable to small molecules (O2 and CO₂) and small hydrophobic molecules (steroid hormones)

Answer 93

* Fluid lipid bilayer with proteins floating in it. * Proteins and lipids can freely diffuse laterally, but flip flops are rare * Membranes have appropriate fluidity for performing biological functions for a given temperature.

Answer 94

**Liquid-ordered state (L_o)**: When T is below the appropriate temperature for optimal membrane fluidity (Tm), phase transition occurs and lipids become semi-solid or gel-like. **Liquid-disordered state (L_d)**: When T is above the appropriate temperature for optimal membrane fluidity (T\>T_m), lipids become more disordered and the membrane becomes too fluid.

Answer 95

1+2: Changing the FA attached to phospholipids: shorter FA \> lower T_m,greater degree of saturation \> higher T_m. 3. Animals control fluidity by using cholesterol to adjust the orderered packing of FA acyl chains.

Answer 96

**Cholesterol broadens the range of appropriate membrane fluidity.** ## Footnote **Below T_m** - cholesterol prevents tight packing of acyl chains \> slows transition to semi-solid state **Above T_m** - cholesterol prevents rotation of acyl chains \> enhances tight packing of acyl chains \> slows transition to fluid-like state

Answer 97

**Acetyl-CoA carboxylase (ACC)** initiates FA synthesis by converting acetyl-CoA to malonyl-CoA. * ACC adds CO₂ to acetyl-CoA generating 'activated acetyl-CoA' (=malonyl-CoA). * 1 molecule of ATP is hydrolyzed in the process. * ACC has biotin (vitamin B7) as a prosthetic group attached to the Lysine residue of ACC. * Occurs in 2 steps: **1.** ACC-biotin + ATP + HCO₃^- \> ACC-biotin-COO^- + ADP + P_i + H⁺ **2.** ACC-biotin-COO^- + acetyl-CoA \> malonyl-CoA + ACC-biotin (irreversible, committed step) *Note: In a cell there is always CO₂ + H₂O ⇌ HCO₃^- + H⁺*

Answer 98

**Initiation** of FA requires *both* _acetyl-CoA_ and _malonyl-CoA_, whereas **elongation** requires *only* _malonyl-CoA_.

Answer 99

FAS consists of a single polypeptide chain with multiple enzymatic activities and 7 functional domains. Works as a homodimer. *Note: In bacteria these are 7 individual proteins and not a single complex.* 7 domains: KS-MAT-DH-ER-KR-ACP-TE

Answer 100

**KS:** ß-ketoacyl-ACP synthase **MAT:** Malonyl/acetyl-CoA-ACP transferase **DH:** ß-hydroxyacyl-ACP dehydratase **ER:** Enoyl-ACP reductase **KR:** ß-ketoacyl-ACP reductase **ACP:** acyl-carrier protein **TE:** Thioesterase

Answer 101

1. Acyl carrier protein (ACP) contains a long flexible **phosphopantetheine group** (similar to CoASH, dervied from vitamin B5). It can bind acyl groups via reactive thiol and the long flexible arm allows acyl-groups to be moved around from one enzymatic activity to the next. All acetyl or malonyl groups are first loaded onto ACP. 2. Reactive **Cysteine** residue in the ß-ketoacyl ACP synthase (KS) domain can also bind acyl groups.

Answer 102

1. MAT transfers acetyl group from acetyl-CoA to ACP. ACP swings to KS domain where acetyl group is transferred from thiol group of ACP to thiol group of Cys in KS domain. This only happens in round 1. 2. MAT transfers malonyl group from malonyl-CoA to ACP and ACP swings next to KS domain. This happens every round (only difference is length of acyl group attached to KS domain)

Answer 103

KS transfers an acetyl group only malonyl group while carboxyl group leaves as CO₂ (same carbon that was added by ACC in activation step prior). As a result ß-ketoacyl-ACP (e.g., in round 1 acetoacetyl-ACP) is formed.

Answer 104

The addition of CO₂ made the acetyl group more reactive and CO₂ is a good leaving group. This drives the reaction forward since the reaction is irreversible.

Answer 105

Not directly, but it is used by ACC in the preparatory step.

Answer 106

ACP arm loaded with ß-ketoacyl group swings to KR domain (ß-ketoacyl ACP reductase), where ß-ketocarbon is reduced to a hydroxyl group, forming D-ß-hydroxyacyl-ACP. NADPH serves as an electron donor and is converted to NADP⁺

Answer 107

ACP arm with D-ß-hydroxyacyl moves to DH domain (D-ß-hydroxyacyl ACP dehydratase). DH removes H₂O (OH from ß-carbon and H from α-carbon) forming trans-Δ²-enoyl-ACP.

Answer 108

ß-hydroxybutyryl-ACP

Answer 109

*trans*-Δ²-Butenoyl-ACP

Answer 110

Butyryl-ACP

Answer 111

**ß-ketobutyryl-ACP**

Answer 112

ACP arm loaded with *trans*-Δ²-enoyl group swings to ER domain (enoyl-ACP reductase). ER reduces the double bond forming acyl-ACP. NADPH is used as a source of electrons and is oxidized to NADP⁺.

Answer 113

Transfer of the acyl chain from ACP to KS. ACP swings to KS domain and KS transfers acyl group from ACP to Cys in KS domain. The cycle then continues. Note: The original acetyl group is at the end of the growing chain. The chain grows from the carbonyl end.

Answer 114

Palmitoyl-ACP is the final product: requires 7 rounds. Then the TE domain (thioesterase) hydrolyzes the C16 acyl chain from ACP with water (hydrolysis) yielding palmitate.

Answer 115

**FAS (7 rounds)** 1 acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 20 H⁺ \> palmitate + 7CO₂ + 14 NADP⁺ + 6H₂O + 8 CoASH Note: 7 H₂O produced, but one is used by thioesterase (TE) **ACC (7 rxns)** 7 acetyl-CoA + 7 CO₂ + 7ATP + 7H₂O \> 7 malonyl-CoA + 7ADP + 7Pi + H⁺ **Overall** 8 acetyl-CoA + 7ATP + 14NADPH + 6H⁺ + H₂O \> palmitate (C16:0) + 14NADP⁺ + 8CoASH + 7ADP + 7Pi

Answer 116

It can be elongated, desaturated, and branched by separate enzymes. * Palmitate can be desaturated by desaturases that will introduce double bonds using O₂ and NAD⁺ (or NADP⁺) to generate *cis* double bonds. There are several desaturases introducing double bonds at different locations. *Mammals cannot double bond beyond C9, so need to obtain from dietary sources.* * Palmitate can be converted to longer FAs by set of enzymes called elongases. * There are also branching enzymes that can be synthesized from branched FAs from palmitate (some bacteria, sea lions).

Answer 117

False. Mammals cannot induce double bonds beyond C9, so there is a need to obtain them from dietary sources.

Answer 118

Acetyl-CoA is generated by carbohydrate, protein, and FA catabolism in the mitochondrial matrix, but FA synthesis occurs in the cytosol.

Answer 119

_Acetyl-CoA is shuttled to the cytosol in the form of citrate_ (produced in TCA cycle from acetyl-CoA and oxaloacetate by **citrate synthase**) via **citrate transporter**. Once in the cytosol **citrate lyase** uses ATP and converts citrate back to acetyl-CoA and oxaloacetate. Oxaloacetate needs to be transported back to the mitochondria to prevent depletion of the TCA cycle. First oxaloacetate is converted to malate by **malate dehydrogenase** (uses NADH). Malate can be directly transported back to mitochondria via **malate-ketoglutarate transporter** and then converted back to oxaloacetate in the matrix. However, majority of malate is converted to pyruvate by **malic enzyme** producing NADPH (used in FA synthesis). Pyruvate then enters the mitochondria via **pyruvate transporter** where it is converted to oxaloacetate by **pyruvate carboxylase**. *Note: NADPH is also produced by pentose phosphate pathway.*

Answer 120

From left to right: Leucine, Isoleucine, Valine

Answer 121

Isoleucine

Answer 122

Methionine

Answer 123

Methionine

Answer 124

Tryptophan

Answer 125

Tryptophan

Answer 126

Biotin (B7)

Answer 127

Pyridoxine (B6)

Answer 128

Tetrahydrobiopterin

Answer 129

Tetrahydrobiopterin

Answer 130

Lack of the serine protease prevents release of the transcription factor from SREBP that normally turns on HMG-CoA reductase transcription leading to HMG-CoA reductase enzyme expression. Although the metalloprotease is present, it alone cannot release the transcription factor domain. This 2nd cleavage by metalloprotease is somehow dependent on the serine protease performing the 1st cleavage on SREBP. Possible steric hindrance or a conformational change in the substrate.

Answer 131

The serine protease is normally in the Golgi. If serine protease is expressed in the ER, the SREBP will be cleaved already in the ER by the serine protease. Once the cleaved SREBP moves to the Golgi (due to low [cholesterol] signalling), the metalloprotease can perform the 2nd cleavage. This is just like the wild type except the serine protease has pre-cleaved SREBP in cholesterol-independent fashion.

Answer 132

The metalloprotease is normally found in the Golgi, not the ER. The metalloprotease cannot cleave the SREBP without prior cleavage by serine protease. SREBP will not be cleaved by the metalloprotease in the ER, as the serine protease is still residing normally in the Golgi. When SREBP moves to the Golgi, there will be cleavage by the resident serine protease, but no release of the transcription factor domain as there is no metalloprotease present.

Answer 133

Both metalloprotease and serine protease are expressed in the ER. The substrate SREBP also resides there regardless of cholesterol levels. Thus, serine protease (1st) and metalloprotease (2nd) will cleave SREBP releasing the transcription factor into the cytoplasm where it will in turn enter the nucleas and turn ON HMG-CoA reductase gene transcription. High amounts of HMG-CoA reductase are expressed independent of cholesterol concentration.

Answer 134

Schiff Base

Answer 135

Hydrolysis

Answer 136

- 1 phosphate - 1 COO^- +1 NH₃⁺ **NET: -1**

Answer 137

Argininosuccinate synthetase (ASS) Acyl CoA synthetase (ACS)

Answer 138

Glutamine synthetase

Answer 139

Dephosphorylation

Answer 140

Biotin (B7)

Answer 141

Odd numbered fatty acids are **directly** broken down into acetyl-CoA and **propionyl-CoA** (which is in turn converted to succinyl-CoA and enters the TCA cycle)

Answer 142

**d.** This molecule is squalene. It is a cholesterol synthesis pathway intermediate and contains 6 isoprenoid units.

Answer 143

**a.** arachidonic acid

Answer 144

**b.** Asp and alpha-ketoglutarate at the active site are required for the formation of pyridoxamine phosphate (PMP).

Answer 145

Farnesyl pyrophosphate

Answer 146

**Lipoprotein particles** Note: albumin transports FAs not TAGs nor cholesterol

Answer 147

**A and C**

Answer 148

**c.** The last product, W, is likely to be a negative modulator of X, leading to feedback inhibition.

Answer 149

Cofactors: pyridoxal phosphate Enzymes: likely alanine aminotransferase or another aminotransferase

Answer 150

The newborn is growing and thus synthesizing all tissue including skeletal muscles and other proteins. This requires the input of all 20 amino acids. Phenylalanine is an essential amino acid and cannot be synthesized in humans and must be obtained from the diet. As such, some phenylalanine will have to come from the diet. A phenylalanine-free diet would prevent new proteins from forming, over and beyond that from protein turnover (no net positive gain). Thus, just the right amount of phenylalanine has to be given. Too little and growth retardation incurs. Too much and mental retardation from PKU symptoms results. Also, phenylalanine is a precursor for Tyrosine. If phenylalanine is missing, then Tyrosine cannot be synthesized. Tyrosine is necessary to make other vital biomolecules such as hormones (epinephrine) and neurotransmitters (DOPA, dopamine, norepinephrine). Lack of these is also associated with mental retardation.

Answer 151

* Carnitine is required to transport fatty acyl CoA into the mitochondrial matrix for ß-oxidation. The inhibition or transport due to deficiency of carnitine diminishes energy production from fats for muscular work. * Excess fatty acyl CoA can be converted to TAGs in muscular cells that normally would not have TAGs. * Since carnitine is not needed for transport of pyruvate (the product of glucose breakdown in the cytosol) into the mitochondrial matrix for oxidation, muscle glycogen metabolism is not affected in people with carnitine deficiency.

Answer 152

The NADH generated by glycolysis can be transformed into NADPH by the combined action of 2 cytosolic enzymes of the citrate transport system. Cytosolic malate dehydrogenase uses NADH to reduce oxaloacetate to malate. Malate then passes the electrons to NADP⁺ to form NADPH (via malic enzyme reaction).

Answer 153

The reactions catalyzed by aminotransferases in the liver are reversible, and many aminotransferases use Glutamate as the alpha-amino group donor. After ¹⁵N-labelled Glutamate is formed by aspartate aminotransferase (AST), the ¹⁵N atom will be quickly distributed among the other amino acids that are products of other aminotransferases

Answer 154

Carbohydrates (glycogen) in cytosol \> glycogen breakdown produces glucose via glycolysis \> condense with oxaloacetate (citrate synthase) to form citrate in the mitochondrial matrix \> transported to cytosol via citrate transporter \> citrate lyase breaks it down to acetyl-CoA and oxaloacetate \> acetyl-CoA carboxylase forms malonyl-CoA \> acetyl-CoA and malonyl-CoA are used by fatty acid synthase to form \> palmitate (a fatty acid) \> then elongases and desaturases make C18+ and unsaturated Fas, respectively.

Answer 155

* Ketosis is production of _excess_ ketone bodies, or high amonts of ketone bodies in the blood. * Occurs during starvation, binge drinking, and type I diabetes * Three ketone bodies: acetone, acetoacetate, ß-hydroxybutyrate * Exclusively ketogenic amino acids: Leucine and Lysine (both are essential) * Amino acids not required for protein synthesis: Ornithine, citrulline, and argininosuccinate

Answer 156

* One micelle = 149,340 g/mol and comprised of LPC = 524 g/mol. Therefore 149,340/524 = 285 LPC molecules in one micelle. * LPC has only 1 tail and 1 large polar head group, which has a cone shape which favours micelle formation. * PC has 2 tails (both saturated) and will have a cyllinder shape. This favours bilayer structures such as biological membranes or liposomes or vesicles.

Answer 157

There is a lack of oxaloacetate in the liver, causing excess acetyl-CoA to build-up. Ketone bodies are formed as a result.

Answer 158

The liver cells do not express high quantities of **ß-ketoacyl CoA transferase,** an enzyme that is important for ketone body catabolism.

Answer 159

C8:0-ACP + malonyl-CoA + 2NADPH + 2H⁺ \> C10:0-ACP + 1CO₂ + 2NADP⁺ + 1H₂O + 1CoA

Answer 160

Carnitine acyltransferase I (CATI)

Answer 161

OKAY AM CONFUSED

Answer 162

When a chiral carbon is formed during ß-oxidation, the chiral carbon is in the L-configuration.

Answer 163

When a chiral carbon is formed during FA synthesis, the chiral carbon is in the **D-configuration.**

Answer 164

Produced as product

Answer 165

ß-oxidation occurs in the mitochondrial matrix. FA synthesis occurs in the cytosol.

Answer 166

A long chain fatty acid attached to a long chain alcohol through an ester linkage.

Answer 167

The reaction catalyzed by malic enzyme and the pentose phosphate pathway.

Answer 168

**b. an increase in the activity of protein kinase A (PKA)**

Answer 169

**C. Every carbon atom.**

Answer 170

**B. Only the omega-carbon atom (furthest carbon from C-1).**

Answer 171

12 oxidation reactions 7 hydration reactions

Answer 172

It enters the citric acid cycle as succinyl CoA.

Answer 173

c. phosphate + 2 fatty acids + glycerol + choline

Answer 174

D. Lysophosphatidylethanolamine (Lyso-PE)

Answer 175

Alanine and glutamine

Answer 176

Arginine and citrulline

Answer 177

A. The concentration of LDLs is increased in the bloodstream.

Answer 178

The release of VLDLs from the liver to deliver TAGs to extrahepatic tissues.

Answer 179

Structure E.

Answer 180

No, it is located in the mitochondrial matrix.

Answer 181

No, it is located in the cytoplasm.

Answer 182

Phenylpyruvate

Answer 183

**Fumarate and acetoacetyl CoA only**

Answer 184

2 fatty acids, glycerol, phosphate, serine

Answer 185

Adenylate (AMP)

Answer 186

C. Contain a prosthetic group derived from vitamin B6

Answer 187

Succinyl-CoA

Answer 188

Acetyl-CoA

Answer 189

ß-hydroxybutyrate

Answer 190

Prostaglandins

Answer 191

**Thromboxanes** and **prostaglandins**

Answer 192

TE - thioesterase

Answer 193

1. TAGs are _highly reduced_! Lots of electrons can be extracted from the FAs of TAGs to make NADH and FADH₂. Polysaccharides are not as reduced. 2. TAGs are _hydrophobic_ (non-polar) so they do not attract H₂O molecules. Since much of our adipose tissue is composed of TAGs there is no extra H₂O weight.

Answer 194

TAGs are non-polar and not amphipathic. In order for lipids to form bilayers they must be amphipathic and exhibit a 3D cylindrical shape. TAG has neither of these qualities.

Answer 195

Phenylalanine hydroxylase uses 1 NADH (via THB) resulting in the loss of 2.5 ATP equivalents. Phenylalanine is converted to Tyrosine when initially catabolized. The enzyme responsible for this hydroxylation is Phenylalanine hydroxylase.

Answer 196

All phosphorylated

Answer 197

C8:0-ACP + 2NADPH + 2H⁺ + malonyl-CoA \> 1CoA + 2NADP⁺ + 1CO₂ + 1H₂O + C10:0-ACP

Answer 198

A & B are False C & D are True

Answer 199

* TAG in adipose is broken into glycerol and FA * FAs can be transported by bloodstream complexed with albumin * Tissues can pick up FAs from the blood and use it for energy * Final product of FA breakdown is acetyl CoA (same as carbs and protein) * Acetyl-CoA enters TCA cycle where it produces NADH and FADH₂, which is ultimately used for ATP production

Answer 200

* Catalyzed by acyl-CoA synthetase (ACS) * ACS links FA to CoA-SH in the cytosol - 2 step process. * Step 1: AMP is attached to FA forming fatty acyl-adenylate * Step 2: CoA-SH displaces AMP formin acyl-CoA * This reaction uses 1 molecule of ATP but 2 ATP equivalents * Both steps are reversible, but hydrolysis of pyrophosphate drives the overall reaction, so it becomes irreversible

Answer 201

* Acyl-CoA cannot cross the inner mitochondrial membrane (IMM). * Carnitine is used as a shuttle to move acyl groups into the mitochondrial matrix. * Requires 3 proteins * **Carnitine Acyl Transferase I (CATI)** transfers acyl chain from CoA-SH to carnitine on the outer mitochondrial membrane * **Carnitine Translocase** transports acyl carnitine across the IMM. * **Carnitine Acyl Transferase II (CATII)** is associated with IMM and transfers acyl chain from carnitine to CoA-SH (rate limiting step)

Answer 202

**Acyl-CoA dehydrogenase** induces a double bond between C2 and C3 (α and ß carbons) using FAD as electron acceptor and generating FADH₂ and *trans*-enoyl-CoA.

Answer 203

**Enoyl-CoA hydratase** adds water across the double bond resulting in L-ß-hydroxyacyl-CoA. This reaction is *stereospecific*.

Answer 204

**ß-hydroxyacyl dehydrogenase** converts L-ß-hydroxyacyl-CoA to ß-ketoacyl-CoA using NAD+ as an electron acceptor. (i.e., NAD+ is the oxidizing agent, and is itself reduced to NADH + H⁺).

Answer 205

Thiolysis is catalyzed by **thiolase** which uses CoA-SH to cleave off acetyl-CoA, leaving acyl-CoA two carbons shorter. *The cycle continues until the acyl chain is completely broken down.* Note: The acyl group is attached to the new Co-A molecule.

Answer 206

Palmitoyl-CoA (C16:0) + 7FAD + 7NAD⁺ + 7H₂O + 7CoA-SH \> 8 acetyl-CoA + 7FADH₂ + 7NADH + H⁺

Answer 207

* Mono-unsaturated FAs require **Δ³, Δ² - enoyl-CoA isomerase** to reposition the double bond to allow hydration by **enoyl-CoA hydratase**. * FADH₂ is not produced because C2-C3 bond is already oxidized, so there will be less ATP produced.

Answer 208

Odd-numbered FAs are broken down to acetyl-CoA and **one** propionyl-CoA, which is converted indirectly (in 3 steps) to succinyl-CoA, which can enter the TCA cycle. The net ATP yield from the conversion of propionyl-CoA to succinyl-CoA followed by its complete oxidation in the TCA cycle is 4 ATP. *Recall: Acetyl-CoA nets 10 ATP from the TCA cycle.*

Answer 209

**_FA synthesis_** * Occurs during times of plenty, (ATP high) * Occurs in adipose, liver, mammary glands * Occurs in the cytosol * 2 carbons are added at a time * Substrates: acetyl-CoA and malonyl-CoA * Performed by one super enzyme complex with 7 domains and involves ACC as well. * NADPH and ACP are used * Intermediate: D-ß-hydroxyacyl-ACP **_FA degradation_** * Occurs during times of starvation (ATP low) * Occurs in most tissues except the brain. * Occurs in the mitochondrial matrix * 2 carbons are removed at a time * Products: acetyl-CoA (as well as propionyl-CoA for odd-numbered FAs) * Requires multiple enzymes and involves ACS as well. * FAD, NAD⁺, and CoA-SH are used. * Intermediate: L-ß-hydroxyacyl-CoA

Answer 210

1. **Acetyl-CoA carboxylase (ACC)** - catalyzes the commited step of FA synthesis - regulated both allosterically and by hormone induced reversible phosphorylation. 2. **Carnitine Acyl Transferase I (CATI)** - allosterically inhibited by malonyl-CoA (substrate of FA synthesis) 3. **ß-hydroxyacyl-CoA dehydrogenase** - inhibited by NADH (product inhibition) 4. **Thiolase** - inhibited by acetyl-CoA (product inhibition)

Answer 211

1. **ACC is regulated allosterically** * Citrate activates ACC: indicates that there is high enough activity of TCA cycle (high acetyl-CoA, high ATP) * Palmitoyl-CoA inhibits ACC: indicates there is enough FA inside the cell 2. **ACC is regulated by hormones via reversible phosphorylation** * ****Glucagon (released by pancreas α-cells when blood glucose is low) will activate via signalling cascade protein kinase A (PKA), which in turn phosphorylates (deactivates) ACC * Insulin (released by pancreas ß-cells when blood glucose is high) will activate via signalling cascade phosphatase, which in turn dephosphorylates (activates) ACC 3. **ATP/AMP levels can change phosphorylation status of ACC** * AMPK (AMP-dependent kinase) is activated by AMP (indicates low energy levels) or deactivated by ATP (indicates high energy levels). * When AMPK is active it will phosphorylate ACC and deactivate FA synthesis.

Answer 212

Malonyl-CoA allosterically inhibits carnitine-acyl transferase I (CATI), so when FA synthesis is activated FA transport into mitochondria will be inhibited.

Answer 213

ß-hydroxyacyl-CoA dehydrogenase is inhibited by NADH (product inhibition).

Answer 214

Thiolase is inhibited by acetyl-CoA (product inhibition).

Answer 215

27 carbon molecule - all carbons are derived from acetyl-CoA

Answer 216

* Stabilizes membrane fluidity * Precursor for steroid hormones (e.g., testosterone, estrogen) * Precursor of bile salts (e.g., taurocholic acid) NOTE: excess dietary cholesterol can be deposited on the blood vessels and lead to atherosclerosis

Answer 217

1. Diet (mostly from animal products) 2. Synthesis Note: Mammals cannot break down cholesterol back to acetyl-CoA

Answer 218

In the liver (some in the intestines) - complex - do not cover all 30 reactions in BIOC 302. Cholesterol synthesis takes place in the cytoplasm and in the endoplasmic reticulum (ER). The first step in the pathway catalyzed by **3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGCS)** occurs in the cytosol while the subsequent steps occur in the ER.

Answer 219

1. **Conversion** of acetyl-CoA into two 5C activated *_isoprenoid_* *_molecules_*. 2. **Condensation** of 6 activated isoprenoids to form 30C *_squalene_* 3. **Cyclization** of squalene and subsequent rearrangement to form *_cholesterol_* (27C)

Answer 220

**IPPP/DMAPP synthesis - occurs in the cytosol** 1. Condensation of 2 acetyl-CoA by ***thiolase*** (reverse of thiolysis step of ß-oxidation) to form *_acetoacetyl-CoA_* (4C) 2. Condensation of acetoacetyl-CoA and acetyl-CoA by ***HMG-CoA synthase*** to form *_HMG-CoA_* (6C)

Answer 221

**ß-hydroxy-ß-methylglutaryl-CoA** **(HMG-CoA)**

Answer 222

**ß-hydroxy-ß-methylglutaryl-CoA** **(HMG-CoA)**

Answer 223

Acetoacetate (ketone body)

Answer 224

Cholesterol

Answer 225

Acetoacetyl-CoA

Answer 226

2 acetyl-CoA

Answer 227

**ß-hydroxy-ß-methylglutaryl-CoA** **(HMG-CoA)**

Answer 228

Reduction of HMG-CoA by **HMG-CoA reductase** using NADPH to form **mevalonate** (6C). This is the *_irreversible_* (committed step) and therefore a site of regulation. This step and all further steps of *de novo* cholesterol synthesis occur on the outer leaflet of the smooth endoplasmic reticulum.

Answer 229

Through a series of reactions mevalonate is converted to activated isoprenoids: **isopentenyl pyrophosphate** (**IPPP**) or **dimethylallyl** **pyrophosphate** (**DMAPP**). 3 ATPs are consumed and 1 carbon is lost in the form of CO₂.

Answer 230

IPPP and DMAPP

Answer 231

Mevalonate

Answer 232

5-Phosphomevalonate

Answer 233

5-Pyrophosphomevalonate

Answer 234

3-phospho-5-pyrophosphomevalonate

Answer 235

Δ³-Isopentenyl pyrophosphate (IPPP)

Answer 236

Dimethylallyl pyrophosphate (DMAPP)

Answer 237

Geranyl pyrophosphate

Answer 238

Farnesyl pyrophosphate

Answer 239

**Synthesis of squalene** 1. Condensation of IPPP and DMAPP in a head-to-tail arrangement by **dimethylallyl pyrophosphate prenyl transferase** to form *_geranyl pyrophosphate_* (10C) 2. Condensation of geranyl pyrophosphate and IPPP in a head-to-tail arrangement by **prenyl transferase** to form *_farnesyl pyrophosphate_* (15C) 3. Condensation of two farnesyl pyrophosphates in head-to-head orientation by **squalene synthase** using *_NADPH_* to form *_squalene_* (30C)

Answer 240

False. * Dimethylallyl pyrophosphate prenyl transferase reaction is IPPP and DMAPP in **head-to-tail** arrangement. * Prenyl transferase reaction is geranyl pyrophosphate and Δ³-Isopentenyl pyrophosphate (IPPP) in **head-to-tail** arrangement. * Squalene synthase reaction is two farnesyl pyrophosphates (15C+15C) in **head-to head** arrangement.

Answer 241

3 ATP Note: 1 carbon is lost as CO₂

Answer 242

Reduction of HMG-CoA by **HMG-CoA reductase** using NADPH to form *_mevalonate_* (6C).

Answer 243

Squalene 2,3-epoxide

Answer 244

Squalene 2,3-epoxide

Answer 245

Lanosterol

Answer 246

1. Cyclization of squalene via a series of reactions to form lanosterol. * Hydroxyl group is added which requires NADPH and O₂. 2. Lanosterol is converted to cholesterol (19 reactions!) with the removal of 3 methyl groups (30C\>27C) and using NADPH as a reducing agent.

Answer 247

HMG-CoA reductase - the enzyme that catalyzes the committed step (mevalonate synthesis) This enzyme is regulated both locally and hormonally.

Answer 248

1. **Transcription of HMG-CoA reductase is controlled by cholesterol** * Sterol regulatory element (SRE) is a sequence of DNA near the HMG-CoA reductase gene that can be recognized by SRE binding protein (SREBP) * When cholesterol levels are high SREBP is anchored in the ER membrane * When cholesterol levels are low SREBP is translocated to the Golgi, where it is cleaved twice by proteases and freed from the membrane. * Free SREBP diffuses to the nucleus and activates transcription of HMG-CoA reductase. * Note: Free SREBP is rapidly degraded to prevent overproduction of cholesterol 2. **Translation of HMG-CoA reductase mRNA is inhibited by mevalonate derivatives** 3. **Degradation of HMG-CoA reductase is stimulated by lanosterol and 25-hydroxycholesterol**

Answer 249

25-hydroxycholesterol

Answer 250

25-hydroxycholesterol

Answer 251

25-hydroxycholesterol

Answer 252

25-hydroxycholesterol

Answer 253

* HMG-CoA reductase is **activated by insulin** triggered *_dephosphorylation_*. * HMG-CoA reductase is **inhibited by glucagon** triggered *_phosphorylation_*.

Answer 254

* Sterol regulatory element (SRE) is a sequence of DNA near the HMG-CoA reductase gene that can be recognized by SRE binding protein (SREBP). * When cholesterol levels are high SREBP is anchored in the ER membrane. * When cholesterol levels are low SREBP is translocated to the Golgi, where it is cleaved twice by proteases and freed from the membrane. * Free SREBP diffuses to the nucleus and activates transcription of HMG-CoA reductase. * Free SREBP is rapidly degraded to prevent overproduction of cholesterol.

Answer 255

1. Cholesteryl esters 2. Bile salts 3. Steroid hormones

Answer 256

* FAs can be attached to the OH group of cholesterol making it more hydrophobic. * Cholesteryl esters are used to store and transport cholesterol (lipoproteins). * Synthesized in the liver by **acyl-CoA cholesterol transferase** (ACAT) using FA-CoA and producing CoA-SH * Also synthesized are high density lipoprotein particles (HDL) by **lecithin cholesterol acyl transferase** (LCAT) using *phosphatidylcholine* and producing *lysophosphatidylcholine*.

Answer 257

Phosphatidylcholine

Answer 258

Cholesteryl oleate | (A cholesteryl ester)

Answer 259

Cholesteryl Ester (with C17:1 acyl group)

Answer 260

Lysophosphatidylcholine

Answer 261

* Polar derivatives of cholesterol synthesized in the liver and stored in the gallbladder. * Help to emulsify dietary lipids in small intestines * Major way to excrete cholesterol

Answer 262

Pregnenolone (C21)

Answer 263

Pregnenolone (C21) - precursor to all steroid hormones

Answer 264

**Progesterone** * Involved in ovarian cycle * Prepares lining of uterus for ovum implantation

Answer 265

**Aldosterone** * Causes kidney to reabsorb Na⁺ and excrete K⁺ * Increases blood volume and pressure

Answer 266

**Testosterone** * Causes development of male * And female secondary sexual characteristics

Answer 267

**Estradiol** * Causes development of male * And female secondary sexual characteristics

Answer 268

**Cortisol** * Inhibits inflammation * Promotes gluconeogenesis and glycogen formation * Promotes fat and protein breakdown

Answer 269

**Cortisol** * Inhibits inflammation * Promotes gluconeogenesis and glycogen formation * Promotes fat and protein breakdown

Answer 270

**Progesterone** * Involved in ovarian cycle * Prepares lining of uterus for ovum implantation

Answer 271

**Aldosterone** * Causes kidney to reabsorb Na⁺ and excrete K⁺ * Increases blood volume and pressure

Answer 272

**Testosterone** * Causes development of male * And female secondary sexual characteristics

Answer 273

**Estradiol** * Causes development of male * And female secondary sexual characteristics

Answer 274

1. **Progestagens** (e.g., progesterone) 2. **Mineralocorticoids** (e.g., aldosterone) 3. **Glucocorticoids** (e.g., cortisol) 4. **Androgens** (e.g., Testosterone) 5. **Estrogens** (e.g., Estradiol)

Answer 275

False. Steroid hormones are more oxidized than cholesterol, they have the C17 alkyl chain removed so they are more polar as well.

Answer 276

False. Steroid hormones can cross biological membranes and can bind DNA or intracellular receptors.

Answer 277

* They are polar derivatives of cholesterol synthesized in the liver and stored in the gallbladder. * They help to emulsify lipids in small intestines.

Answer 278

In the intestines they are broken down by amylase, sucrase, maltase, and lactase into monosaccharides.

Answer 279

Lipids (TAG) are first emulsified by bile (bile salts + choesteryl esters) into micelles and then broken down by lipases to monoacylglycerol (MAG) and 2 FAs.

Answer 280

Water is used to break down TAG to MAG.

Answer 281

Monosaccarides are absorbed via facilitated diffusion using membrane transporters into the bloodstream and into the portal vein.

Answer 282

* MAG and FAs are absorbed via facilitated diffusion using membrane transporters. * Inside intestinal cells TAG are reassembled and packaged with cholesterol and apolipoproteins into lipoprotein particles called **chylomicrons**. * Chylomicrons are released via lacteal (lymphatic system capillary) and *_travel via lymphatic system bypassing liver._*

Answer 283

* Monosaccharides (mainly glucose) are distributed by bloodstream and taken up by tissues by facilitated diffusion using membrane transporters (e.g., GLUT4) and used for energy or stored (in liver and muscle as glycogen).

Answer 284

* Lymphatic system carrying chylomicrons merges with bloodstream. * Chylomicrons are distributed by bloodstream to tissues and where endothelial cells express tissue lipoprotein lipase, cleaves TAG to 3 FAs and glycerol, which in turn are picked up by tissues and used for energy (e.g., muscle) or stored (re-esterified to TAG in adipose tissue).

Answer 285

1. Chylomicrons: large and very low density 2. Very low density lipoprotein (VLDL) 3. Low density lipoprotein (LDL) 4. High density lipoprotein (HDL)

Answer 286

Large and very low density lipoprotein particles that contain primarily dietary TAG and small amounts of cholesterol. Remnants of chylomicrons are picked up by the liver.

Answer 287

* Low density lipoprotein particle that transports endogenous cholesterol from liver to tissues. * ApoB100 in LDL is recognized by LDL receptor in tissues and picked up by endocytosis. * 'Bad cholesterol' - high levels are associated with obesity, diabetes, and heart disease. * Excessive amounts can be deposited on capillary walls leading to atherosclerosis. * Image on other side: peripheral tissue uptake of cholesterol by LDL (ApoB100)-receptor mediated endocytosis

Answer 288

* Very low density lipoprotein - transport of endogenously synthesized TAG from the liver to peripheral tissues including adipocytes. * Remnants of VLDL are converted to LDL or picked up by the liver in the form of IDL. * e.g., excessive (glucose\>acetyl-CoA\>FAs)_liver \>VLDL\>adipose tissue

Answer 289

* High density lipoprotein particle - transports endogenous cholesterol from tissues to the liver (reverse transport of cholesterol) * 'Good cholesterol' - high levels are associated with normal lipid metabolism. * Liver makes a precursor to HDL that picks up cholesterol from tissues and transports it to the liver where it can be converted to bile to get rid of excessive cholesterol * HDL/LDL is used as a diagnostic.

Answer 290

1. Protein synthesis 2. Carbon source to build other molecules (e.g., glucose, neurotransmitters, etc.,) 3. Energy - during starvation 4. Nitrogen source - for other AA or other N-containing molecules 5. Nitrogen transport

Answer 291

* An interplay between organs and hormones results in activation of dietary proteases (e.g., chymotrypsin) that hydrolyze proteins to individual amino acids * AA are absorbed into the bloodstream, go via portal vein (vein that connects intestines and liver) and then distributed among tissues. * Picked up by AA transporters

Answer 292

1. To breakdown proteins that are not needed anymore - recycling. 2. To remove damaged or misfolded proteins 3. Inactivation of enzymes in metabolic pathways - regulatory (e.g., HMG-CoA reductase, cyclins) 4. For energy - only during prolonged starvation **All proteins are continually synthesized and degraded - protein turnover.**

Answer 293

* Proteins tagged with a small (8.5kDa) protein called ubiquitin are targeted to degradation. * C-terminus of ubiquitin (Ub) forms isopeptide bond with epsilon-amino group of Lysine's side chain in target protein

Answer 294

* Ubiquitination of proteins. * C-terminus of ubiquitin forms isopeptide bond with epsilon-amino group of Lysine's side chain in target protein.

Answer 295

**Multistep process requiring 3 enzymes** * E1 - Ub-activating enzyme (UbA) 1 gene * E2 - Ub-conjugating enzyme (UbC) several genes * C3 - Ub-ligase (UbL) - several hundred genes **Step 1a** - E1 adenylates Ub forming Ub-AMP (*_2 ATP equivalents are used_*) **Step 1b** - Ub is transferred onto Cys residue of E1. **Step 2** - E2 transfers Ub from E1 to E2. **Step 3a** - E3 recognizes and binds target protein and Ub-E2 **Step 3b** - E3 transfers Ub from E2 to Lys of target protein forming isopeptide bond. Note: sometimes other AA can be ubiquitinated (e.g., Cys)

Answer 296

4 on average (8 ATP cost) Note: Ubiquitin is a protein with a Lys residue that can be tagged by another Ubiquitin.

Answer 297

False. Non-lysine ubiquitination is rare but possible. Cysteine is one of the AA that can be ubiquitinated.

Answer 298

If a protein has Met at the N-end then it usually has a longer half-life, and if it has another AA (e.g., Arg), it has a shorter half-life.

Answer 299

* 26S complex (64 subunits) that degrades Ub-proteins * Forms a hollow tube open at both ends. * Two 19S caps recognize Ub-proteins and denature it * Denatured proteins are fed into the 'tube' (requires ATP), while Ub is cleaved off for reuse. * The 'tube' (20S core) degrades target proteins into small peptides that are released into the cytosol where they can be further degraded by cellular peptidases

Answer 300

* Nitrogen in the form of amino group can be removed from AA by aminotransferases (aka transaminases): amino group of one AA is transferred to alpha-ketoacid forming another AA. Usually it is alpha-ketoglutarate and glutamate is formed.

Answer 301

An amino acid that has lost its amino group and contains carbonyl at its place.

Answer 302

Aspartate + alpha-ketoglutarate \> oxaloacetate + Glutamate ^ catalyzed by aspartate aminotransferase (AAT) Alanine + alpha-ketoglutarate \> pyruvate + Glutamate ^ catalyzed by alanine aminotransferase (ALT)

Answer 303

Occurs in the cytosol of peripheral tissues but the main site is the liver (can use blood ALT levels as diagnostic tool for liver damage)

Answer 304

* All aminotransferases have the same prosthetic group - PLP (pyridoxal phosphate) - tightly bound in the active site by non-covalent interactions. * PLP is derived from pyridoxine (B6) and has a highly reactive aldehyde group * Aldehyde group of PLP will react with amino group of AAs forming aldimine (Schiff base)

Answer 305

In resting state the aldehyde group of PLP is in Schiff base with amino group of enzyme's Lysine: Lys(ε)-PLP

Answer 306

**Ping-pong reaction mechanism** **1.** AA that needs to be degraded enters the active site and displaces the Enz-Lys to form Schiff base with PLP. (AA1 + Lys(ε)-PLP -\> Lys(ε)-NH2 + AA1-PLP) **2-4.** Schiff base rearrangement and hydrolysis resulting in the release of alpha-ketoacid and formation of pyridoxamine phosphate (PMP) (AA₁-PLP + H₂O \> alpha-ketoacid₁ + PMP) **5.** Alpha-ketoacid₂ (usually alpha-ketoglutarate) enters the active site and its carbonyl will react with the amino group of PMP forming another Schiff base. **6-7.** Rearrangement - reverse of 2 and 3. **8.** Reversal of step 1 - enzyme's Lys displaces AA₂ (usually glutamate), releasing AA₂ and reforming Lys(ε)-PLP. (PMP + alpha-ketoacid₂ + Lys(ε)-NH₂ \> Lys(ε)-PLP + AA₂ + H₂O) Overall: AA₁ + alpha-ketoacid₂ \> AA₂ + alpha-ketoacid₁

Answer 307

1. **Glutamine**: peripheral cells that produce glutamate via transamination and NH₄⁺ from metabolic reactions. * Glu + NH₄⁺ \> Gln + H₂O (uses ATP) * Above reaction done by **glutamine synthetase** 2. **Alanine**: (Cahill cycle -glucose-alanine cycle) * In muscle during heavy exercise exessive amounts of pyruvate are produced along with excessive amounts of NH₃produced from AA catabolism. * Pyruvate can be transaminated to form alanine and then delivered to the liver where it forms back the pyruvate then used for gluconeogenesis and glutamate (transamination again)

Answer 308

Glu \> alpha-ketoglutarate + NH₄⁺ Oxidative deamination catalyzed by **glutamate dehydrogenase** using NAD⁺ or NADP in the mitochondrial matrix.

Answer 309

Gln H₂O \> Glu + NH₄⁺ Deamination catalyzed by glutaminase in the mitochondrial matrix

Answer 310

* Excreted directly - only in aquatic animals * Form urea - land animals such as mammals or amphibians * Form uric acid - land animals such as reptiles and birds

Answer 311

NH₄⁺ + HCO₃^- + 3ATP + Asp + H₂O \> Urea + fumarate + 2ADP + 2Pi + AMP + PP + 4H⁺

Answer 312

* Synthesis of carbamoyl phosphate from ammonia and bicarbonate * Catalyzed by **carbamoyl phosphate synthetase** (CPS-1) * Requires 2 ATP * Occurs in the mitochondrial matrix - 3 steps: 1. Bicarbonate is phosphorylated by ATP to form **carboxyphosphate** (highly reactive) 2. NH₃ displaces the phosphate to form **carbamate** 3. Carbamate is phosphorylated by ATP to form **carbamoyl phosphate**

Answer 313

Carboxyphosphate

Answer 314

Carboxyphosphate

Answer 315

1. **Carbamoyl phosphate reacts with amino acid ornithine to form amino acid citrulline in the mitochondrial matrix.** * Catalyzed by ornithine transcarbamylase (OTC) * Pi is displaced * Citrulline is transported to the cytosol 2. **Citrulline is activated by ATP and then reacts with aspartate to form argininosuccinate** * Catalyzed by argininosuccinate synthase * AMP and PP are formed (2 ATP equivalents are used) 3. **Argininosuccinate is cleaved to form fumarate and arginine** * Catalyzed by argininosuccinase 4. **Arginine is hydrolyzed to generate urea and ornithine** * Catalyzed by arginase * Ornithine is transported back to the mitochondrial matrix

Answer 316

Citrulline

Answer 317

Argininosuccinate

Answer 318

In the mitochondrial matrix it catalyzes the reaction between carbamoyl phosphate and ornithine to form citrulline. Pi is displaced. This is step 1 of the urea cycle. Citrulline is transported to the cytosol.

Answer 319

Citrulline is activated by ATP and then reacts with aspartate to form argininosuccinate. This is catalyzed by argininosuccinate synthetase. 2 ATP equivalents are used in this reaction, and AMP and PP are formed. This is the 2nd step of the urea cycle.

Answer 320

Cleaves argininosuccinate to form fumarate and arginine This is the 3rd step of the urea cycle.

Answer 321

Hydrolyzes arginine to generate urea and ornithine. The ornithine is transported back to the mitochondrial matrix. This is the last step of the urea cycle.

Answer 322

The urea is released into the bloodstream, where it is filtered out by the kidneys to form urine and eventually excreted.

Answer 323

From glutamate and oxaloacetate by aspartate aminotransferase

Answer 324

It can be converted to malate first by **cytoplasmic fumarase**, and then malate can be transported back to the mitochondrial matrix where it is converted to oxaloacetate by **malate dehydrogenase**.

Answer 325

True. e.g., Argininosuccinase deficiency: Argininosuccinate will accumulate and cannot be cleaved to Arg and fumarate. The urea cycle will stall and ammonia will start to build up.

Answer 326

Argininosuccinate will accumulate if argininosuccinase is deficient. Since it cannot be cleaved to Arginine and fumarate the urea cycle stalls and ammonia will start to build up. Treatment: 1. Arginine and aspartate supplementation - bypass block and argininosuccinate is excreted in the urine. Allows ammonia and Aspartate to flow again. 2. Eat very low protein diet.

Answer 327

* Formation of N-acetylglutamate from acetyl-CoA and glutamate by N-acetylglutamate synthase * N-acetylglutamate is an allosteric activator of CPS-1 * N-acetylglutamate is formed when Glutamate levels are high * Arginine is a positive regulator of N-acetylglutamate synthase

Answer 328

* Regulation of express of genes encoding urea cycle enzymes * Diets that have high protein content and starvation will result in elevated levels of urea cycle enzymes

Answer 329

1. Pyruvate 2. alpha-ketoglutarate 3. Succinyl-CoA 4. Fumarate 5. Oxaloacetate 6. Acetyl-CoA 7. Acetoacetyl-CoA All 7 can feed into the TCA cycle. 1 -5: glucogenic AA, meaning we can use them to make glucose via gluconeogenesis 6 and 7: cannot be converted to glucose, but can be converted to ketone bodies

Answer 330

* Both are gluconeogenic and ketogenic * Transamination happens on the second step Overview 1. Phe is converted to Tyr by **phenylalanine hydroxlyase (PAH)** using O₂ and cofactors tetrahydrobiopterin (THB) and NADH. As a result Phe is hydroxylated and THB is oxidized to dihydrobiopterin (DHB) and require another enzyme **DHB reductase** to convert it back to THB. 2. Transamination of Tyr by **tyrosine aminotransferase (TAT)** using alpha-ketoglutarate as acceptor of amino group. 3. Reactions 3-7 the carbon skeleton (hydroxyphenylpyruvate) is decarboxylated, hydroxylated, opened, rearranged, and finally split to fumarate and acetoacetyl-CoA.

Answer 331

* Phe is converted to Try using O₂ and cofactors THB and NADH. * As a result Phe is hydroxylated and THB is oxidized to dihydrobiopterin (DHB). * DHB reductase is another enzyme that converts DHB back to THB

Answer 332

DHB reductase and cofactor NADH.

Answer 333

Overview: catabolism of phenylalanine 1. Phe is converted to Tyr by phenylalanine hydroxylase (PAH) using O₂ and cofactors tetrahydrobiopterin (THB) and NADH. As a result Phe is hydroxylated and THB is oxidized to dihydrobiopterin (DHB) and require another enzyme DHB reductase to convert it back to THB. 2. Transamination of Tyr by tyrosine aminotransferase (TAT) using α-ketoglutarate as acceptor of amino group 3. In 5 rxns (3-7) carbon skeleton (hydroxyphenylpyruvate) is decarboxylated, hydroxylated, opened, rearranged, and finally split to fumarate and acetoacetyl-CoA

Answer 334

* Mutation in phenylalanine hydroxylase (phenylketonurio -PKU) leads to build-up of Phe, that will undergo oxidative deamination to produce phenylpyruvate. * Phe and phenylpyruvate are toxic in high concentration * Symptoms: mental retardation and death (if untreated) * Treatment: diet with no Phe and Tyr supplementation * Note: Tyrosine is precursor to neurotransmitters (dopamine, norepinephrine, epinephrine) and for pigment melanin.

Answer 335

Aminotransferases are key in synthesizing AAs, because we can convert one AA into another by transferring amino group to alpha-ketoacid. If we cannot synthesize alpha-ketoacid corresponding to AA then we must get it from the diet. For the rest of AA we can synthesize alpha-ketoacid corresponding to AA so these are non-essential. Glu or Gln supply amino group and carbon skeletons come from TCA or pentose phosphate pathway. (e.g., Arg - 10 steps including urea cycle. Asn - 2 steps from TCA intermediate)

Answer 336

Glu or Gln supply the amino group and carbon skeletons come from TCA or pentose phosphate pathway. (e.g., Arg - 10 steps including urea cycle. Asn - 2 steps from TCA intermediate)

Answer 337

Acetone Acetoacetate D-ß-hydroxybutyrate

Answer 338

Nutrients are broken down by enzymes: proteins (proteases and peptidases: chymotrypsin, pepsin, trypsin) into AAs, lipids (emulsified first) into MAG and 2FAs, and carbohydrates (amylase, lactase, sucrase, etc.) into monosaccharides.

Answer 339

* Monosaccharides (e.g., via SGLT1 transporter for glucose) and AAs (e.g., alanine transporter) are transported to the bloodstream via facilitated diffusion and travel via portal vein to liver first and then to the systemic circulation. * MAG and 2 FAs are reassembled into TAG and then packaged into chylomicrons, and then released into the lymphatic system which bypasses liver.

Answer 340

* Monosaccharides (e.g., glucose - via GLUT4, GLUT2) and AAs (e.g., BCAA transporter) are distributed by bloodstream and taken up by tissues via facilitated diffusion and used for energy (glucose), or to synthesize glycogen (in the liver and muscle from glucose), or synthesizes TAG (excessive amounts of glucose) or synthesize proteins. * Lipids are transported by chylomicrons - dietary TAG are distributed by bloodstream to the tissues where they are released by tissue **lipoprotein lipase**, and then glycerol and 3 FAs are picked up to be used for energy or stored (adipose tissue)

Answer 341

In response to increase in blood glucose. Stimulates glucose uptake (GLUT4), glycogenesis, glycolysis, stimulates AA uptake, protein synthesis, stimulates lipoprotein lipase.

Answer 342

* Glucose can be synthesized via gluconeogenesis in the liver and distributed by bloodstream * Non-essential amino acids can be synthesized and distributed by bloodstream. * Lipids (FA and cholesterol) can be synthesized (mainly in liver) and distributed via lipoproteins (VLDL for TAG, LDL for cholesterol).

Answer 343

* When **glucose** is depleted we start using **glycogen**, and then gluconeogenesis (from glucogenic AAs) is activated. * **Proteins** are not normally used for energy, but during prolonged starvation when gluconeogenesis is activated we see protein breakdown and glucogenic AAs are transaminated and carbon skeletons are used as substrate for gluconeogenesis. * During starvation **TAG** are broken down into glycerol and FAs, and then FAs are carried by albumin to the tissues (liver, muscle, heart) to be used for energy. * **Ketone bodies** are synthesized by liver from acetyl-CoA, and then released to the bloodstream where they are picked up by the brain and heart, where they are converted back to acetyl-CoA and used for energy via TCA cycle. Too many ketones (e.g., diabetes) is toxic.

Answer 344

Glucagon released from pancreatic alpha cells is a major activator of processes during fasting and starvation. Stimulates glycogen breakdown, gluconeogenesis, AA catabolism (increased expression of enzymes of urea cycle), protein degradation, hormone sensitive lipase (via cAMP\>PKA\>phosphorylation), ketogenesis (insulin inhibits ketogenesis.

Answer 345

Glucagon - released from pancreatic alpha cells Insulin - released from pancreatic beta cells

Answer 346

False. Insulin **inhibits** ketogenesis. Glucagon **stimulates** ketogenesis.

Answer 347

True - in large amounts (e.g., diabetes)

Answer 348

A. Which are saturated? _A, B_ B. Which are monounsaturated? _D, F_ C. Which are polyunsaturated? _C, E_ D. Which are not likely to be found in humans? _D, E_ – mammals don’t have desaturases enzymes that can introduce trans bonds or cis double bonds beyond C9.

Answer 349

1. C16:0 or C₁₆:0 or 16:0 2. C18:1 cis Δ⁹ or C₁₈:1 cis Δ⁹ or 18:1 cis Δ⁹ 3. C18:3 cis Δ^9,12,15 or C₁₈:3 cis Δ^9,12,15 or 18:3 cis Δ^9,12,15

Answer 350

All three fatty acids have the same carbon chain length – so this does not have an influence on the difference in melting points. Stearic acid has the highest melting point of the three as it is a *saturated* FA, compared to elaidic and oleic acid which are *monounsaturated* FAs. **The degree of saturation affects melting points because the double bonds create kinks and disrupt van der waals forces, leading to looser packing of fatty acyl chains in a lipid membrane.** Elaidic acid has the second highest melting point as it contains a *trans* double bond on its structure compared to oleic acid which has a *cis* double bond. **_Cis_ bonds create a much more severe kink as compared to trans double bonds, disrupting van de waals forces to a much larger extent than trans double bonds.**

Answer 351

When phytanic acid (branched FA) accumulates in nerve cells there is a disruption of van de waals forces which leads to looser packing of the fatty acids in the cell membrane. This leads to a decrease in melting temperature and hence easier disruption of the nerve cell membranes.

Answer 352

C. The fatty acid moiety is attached via an amide linkage.

Answer 353

It could only be a sphingolipid (sphingomyelin). Fatty acids do not contain inorganic phosphates as part of their structure. Glycerophospholipids have two fatty acyl chains attached to a head group via a phosphoglycerol molecule. Assuming the head group included does not contain any additional phosphate groups, the ratio of fatty acid to inorganic phosphate for a glycerophospholipid would be 2:1. Sphingomyelin has one fatty acid molecule and a phosphocholine head group molecule attached to the sphingosine backbone, for a ratio of fatty acid to inorganic phosphate of 1:1.

Answer 354

Membrane lipids should be amphipathic so that they can arrange in a bilayer with the hydrophobic portion forming the barrier and the hydrophilic portion facing water on both the interior and exterior of the cell. Triacylglycerol is completely hydrophobic, if exposed to an aqueous environment it will aggregate and separate out from water

Answer 355

Melting temperature is lowered – curve shifts to the left. Introducing glycerophospholipids with unsaturated fatty acyl chains would lead to looser packing of the lipids in a membrane, which in turn would decrease melting temperature.

Answer 356

Melting temperature is increased – curve shifts to the right. Introducing glycerophospholipids with longer fatty acyl chains would lead to tighter packing of the lipids in a membrane, which in turn would increase melting temperature.

Answer 357

Cholesterol acts like a fluidity buffer: Below Tm – cholesterol disrupts close packing of acyl chains and increases membrane fluidity. Above Tm – cholesterol constrains motion of acyl chains and decreases membrane fluidity. It essentially broadens the phase transition.

Answer 358

False. Fatty acid synthase catalyzes dehydration reactions not hydration reactions. Hydration is in ß-oxidation during lipid metabolism.

Answer 359

False. FAS uses 2 NADPH to extend the chain length by 2 carbons.

Answer 360

False. The pantothiene group is located in the ACP domain of FAS.

Answer 361

False. FAS acts primarily in the cytoplasm.

Answer 362

A. C8:1 *trans* Δ²-ACP B. See image

Answer 363

After the last round of synthesis, the 16-carbon acyl chain is still attached to ACP via a thioester linkage. The thioesterase enzyme uses 1 molecules of water as a substrate to hydrolyze palmitoyl-ACP and release palmitate.

Answer 364

Acetyl-CoA is the building block for FA synthesis. It needs to be moved from the mitochondria to the cytoplasm for synthesis, via the citrate shuttle. Citrate lyase is required to regenerate acetyl-CoA from citrate in the cytoplasm → this reaction requires 1 ATP. Malate dehydrogenase in cytosol and mitochondrial matrix cancel out. For palmitate, 8 acetyl-CoA need to be transported = 8 ATP (53% of 15 ATP).

Answer 365

In the cytosol, acetyl-CoA carboxylase adds a CO₂ group onto acetyl-CoA to make malonyl-CoA → this costs 1 ATP. 7 malonyl-CoA are needed to make C16:0 = 7 ATP used (47% of 15 ATP).

Answer 366

There are 2 pools of CoA – one in the cytosol and one in the matrix. CoA is replaced by carnitine during the transport, and thus it never goes through the membrane. This is why palmitoyl-CoA isolated from the cytosolic fraction is radioactive, but that isolated from the mitochondrial fraction is not.

Answer 367

The carnitine-mediated transport of fatty acids into mitochondria is the rate-limiting step in ß-oxidation. Carnitine deficiency decreases the rate of transport of fatty acids into mitochondria and thus the rate of ß-oxidation, so addition of carnitine would increase the rate of oxidation

Answer 368

Fasting, exercise, and a high-fat diet all cause an increased need for b oxidation of fatty acids and thus an increased demand for carnitine shuttle activity. The symptoms of carnitine deficiency would therefore become more severe under these conditions.

Answer 369

Final net gain of ATP = 120 ATP + 132.5 ATP + 128ATP + 16 ATP = 396.5 ATP Final net gain of water = 26 H2O + 28 H2O + 28 H2O + 3 H2O – 3 H2O = 82 H2O molecules

Answer 370

Oxidations - 4 Hydrations - 2 Thiolysis - 3 Reductions - 0 Dehydrations - 0 Isomerization - 1

Answer 371

38 ATP 8 H₂O

Answer 372

* ACC is inactive when phosphorylated and the inactive enzyme limits fatty acid synthesis. * During time of need or starvation, glucose levels are low and glucagon is released. * Glucagon binds to the G-protein coupled receptor to activate adenylyl cyclase. * cAMP activates PKA which in turn phosphorylates ACC. * Also, [AMP] in a state of starvation is high. * AMP binds to AMPK which can also phosphorylate ACC. * During a time of plenty, glucose levels are high and insulin is released. * Insulin activates phosphatase which dephosphorylates ACC thereby activating it. * Also, [ATP] is high during a time of plenty and AMPK is inhibited.

Answer 373

Malonyl-CoA can no longer inhibit the activity of CAT I and fatty acid transport into the mitochondrial matrix would continue regardless of the level of malonyl-CoA (no longer slows or stops beta-oxidation). A futile cycle could result where synthesis and breakdown of fatty acids occurs simultaneously.

Answer 374

True - when a meal is ingested, bile salts are released from the gall bladder into the intestine to breakdown macroscopic pieces of fat into microscopic micelles.

Answer 375

True - shortly after eating, Glucose and insulin levels are high. Insulin activates HMG-CoA reductase which increases mevalonate production and upregulates cholesterol biosynthesis.

Answer 376

True - during times of plenty, FA synthesis and cholesterol biosynthesis are upregulated. Both of these pathways utilize NADPH.

Answer 377

False - shortly after eating, glucose levels are high and insulin is released. Insulin activates phosphatase which dephosphorylates ACC, allowing malonyl-CoA formation and fatty acid synthesis.

Answer 378

To make cholesterol more hydrophobic to stay in the interior of plasma lipoproteins.

Answer 379

True - ß-oxidation is upregulated during starvation - carnitine acytransferase I activity is the rate limiting step of the pathway.

Answer 380

False - FA synthesis is downregulated during starvation - ACC would be phosphorylated to prevent malonyl-CoA synthesis - commited step of the pathway.

Answer 381

False - cholesterol biosynthesis is downregulated during starvation - glucagon allosterically inhibits activity of HMG-CoA reductase, preventing formation of mevalonate, the commited step of the pathway.

Answer 382

True - FA synthesis is downregulated so there is no need for transport of acetyl-CoA from the matrix to the cytosol.

Answer 383

True - in a state of starvation blood glucose levels will be very low which leads to secretion of glucagon (starvation signal)

Answer 384

Increase ACC is dephosphorylated when blood glucose levels are high and insulin levels are high. Insulin allosterically activates the activity of HMG-CoA reducase.

Answer 385

Decrease The complex is bound to the ER when intracellular sterol concentration is high →No need for cholesterol biosynthesis, so enzyme activity of HMG-CoA reductase involved in the committed step is decreased.

Answer 386

Increase. DNA-binding domain in the cell nucleus leads to transcription/synthesis of the protein \> only occurs when there is an increased need for the enzyme/activity.

Answer 387

Decrease. Intracellular cholesterol concentration levels can influence the committed step/activity of the enzyme through negative feedback inhibition.

Answer 388

Decrease. Build-up of mevalonate (product of the reaction catalyzed by HMG-CoA reductase) can also influence the enzyme activity through negative feedback inhibition.

Answer 389

Statins having a very similar structure to mevalonate and HMG-CoA can acts as competitive inhibitors of the enzyme HMG-CoA reductase. The reaction catalyzed by this enzyme is the rate limiting step in cholesterol biosynthesis

Answer 390

C. Cholesterol synthesis by hepatocytes is increased.

Answer 391

High LDL to HDL ratio, which is associated with higher risk of cardiovascular disease. LDLs stay in blood for long periods of time, they tend to accumulate and become partially oxidized, forming plaques that block blood vessels.

Answer 392

Mutations in ubiquitin machinery lead to decreased ubiquitination This leads to slower protein turnover and therefore the old and damaged proteins linger in the brain. Aggregation of those proteins lead to build-up of plaques.

Answer 393

The E3 ligase enzyme as this specifically catalyzes the ubiquitination of specific target proteins.

Answer 394

N-terminal rule of ubiquitination: identity of N-terminal amino acid helps determine selection by E3 for ubiquitination. Met is associated with longer half-lives compared to other amino acids like arginine, hence Protein B exists longer than Protein A.

Answer 395

When protein synthesis is fully inhibited, no new proteins can be generated. However, all proteins in the cell will eventually be broken down. When too many proteins are broken down, the cell is no longer able to function properly, and will die. However, different proteins have different half-lives, resulting in different proteins being broken down at different rates. As such, death is not immediate, and the time needed will have a huge variance.

Answer 396

B. The amino group is transferred to the carbon backbone of an α-keto acid (such as α-ketoglutarate) to form the corresponding amino acid

Answer 397

**C. X = alanine**

Answer 398

Alanine and glutamine

Answer 399

The process gets rid of ammonia from the muscle cell and carries it to the liver to be disposed off through the urea cycle. It also generates pyruvate in the liver, which can be converted back to glucose through the glucose-alanine cycle. Glucose goes back to the muscle cell to be used as a source of energy.

Answer 400

* Glutamate is converted to glutamine in extra hepatic cells - 1 ATP * Glutamine is transported through the blood stream and enter the liver mitochondrial matrix * Glutamine is converted back into Glutamate by releasing an NH₄⁺ molecule (side chain amino group) * Free ammonia goes through the CPS 1 reaction to make carbamoyl phosphate – 2 ATP * [Asp] is in low amounts so it must be synthesized via Asp aminotransferase α-amino group from glutamate is transferred onto aspartate * urea cycle: * Argininosuccinate synthetase – 2 ATP (aspartate synthesized in the previous step feeds into this step on the urea cycle; argininosuccinate that is synthesized contains both nitrogen’s brought to the liver via glutamine) * Fumarate through the TCA cycle 1NADH = + 2.5 ATP * Ultimately BOTH amino groups brought to the liver via glutamine will end up on 1 molecule of urea. * Net ATP Cost: – 2.5 ATP

Answer 401

Citrulline

Answer 402

Citrulline

Answer 403

**1. Transcriptional regulation** - upregulates gene expression of urea cycle enzymes under conditions such as a high protein diet or excess starvation, when amount of ammonia is increased. **2. Allosteric regulation** - CPS I is allosterically activated N-acetylglutamate

Answer 404

E. argininosuccinate synthetase deficiency

Answer 405

Addition of arginine stimulates production of ornithine, citrulline and argininosuccinate. Citrulline and argininosuccinate contain the amino group to be excreted, thereby reducing the free ammonia in the body. Arginine is also an allosteric activator of N-acetylglutamate synthase, which produces N-acetylglutamate which further activates CPS1. This increase the amount of ammonia entering the urea cycle.

Answer 406

A. Phenylalanine, pyruvate, alanine B. Aminotransferase C. Accumulation of Phe is a symptom of PKU. Treatment is to limit Phe intake and supplement tyrosine to allow the pathway to proceed.

Answer 407

The drug would also inhibit ketone body synthesis in the liver because the same step is part of ketone body synthesis. When fat is used as a major energy source, organs like the brain, heart, skeletal muscles and renal cortex rely on the supply of ketone bodies from the liver for its function.

MT1 Material Flashcards

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