FINAL EXAM REVIEW CH 7-14

Know the characteristics and functions of eicosanoid hormones

- potent short-range hormones made from arachidonate - ex: prostaglandings, leuoktrienes, thromboxanes - In response to stimuli, phospholipase a2 is activated attacks c2, releasing arachidonate

The activity of enzyme HMG-CoA reductase is present in the ___ domain

transmembrane

HMG- CoA reductase is regulated by

1. covalent modification of HMG-COA reductase 2. transcriptional regulation of HMG COA gene and LDL receptor 3. Proteolytic degradation of HMG COA reductase 4. Activation of ACAT, which increases esterification for storage

2 types of activated isoprenes

1. delta isopentyl pyrophosphate (IPP) 2. dimethylallylpyrophosphate (DMAPP)

Oxidation of unsaturated and polyunsaturated fatty acids require two additional enzymes:

1. isomerase 2. reductase

True or false, fats provide efficient, longer term (months) fuel storage than glucose and glycogen

true

Overview of cholesterol biosynthesis: 1. three acetates condense to form _____ 2. Product from 1 converts to phosphorylated _______ 3. Six products from 2 polymerize to form ______ 4. Product from 3cyclizes to form four rings, producing ______

1. mevalonate 2. 5-c isoprene 3. squalene 4. cholesterol

List the steps of yeast phospholipid synthesis in order:phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine

1. phosphatidylserine 2.phosphatidylethanolamine 3. phosphatidylcholine

Geranyl pyrophosphate (GPP) is a ___ carbon molecule.

10

True or false, fatty acids carry more energy per carbon than polysaccharides

true, because they're more reduced than polysaccharides

What is the effect of levels of ATP on cholesterol synthesis?

Low ATP (high AMP) inhibits HMG-COA Reductase

Malate Dehydrogenase is also known as

MDH

Role of malonyl CoA in fatty acid regulation

Malonyl COA inhibits carnitine acyltransferase I (CAT 1) so it inhibits fatty acid beta oxidation

Differences in oxidation in mitochondria and peroxisome acyl COA dehydrogenase

Mitochondrial: passes e-'s into respiratory chain via electron transferring flavoprotein - energy captured as ATP Peroxisomal/glyoxysomal: passes e-'s directly to molecular oxygen - energy released as heat, hydrogen peroxide eliminated by catalase

Fatty acid synthesis occurs in cell compartments where _____ levels are high

NADPH

Farnesyl pyrophosphate is a __ carbon molecule

15

Define the basic structure of a steroid

17C Four rings

How many ATPs are needed for cholesterol formation?

18 3 for each isoprene, need 6 isoprenes total

How many phosphate groups are transferred from ATP to mevalonate to from 5- pyrophosphate mevalonate?

2

What are the 4 steps of fatty acid synthesis?

C,R,D,R KS, KR, DH, ER Prep: malonyl coa and acetyl coa are bound to FAS1 and lose coa (bind via thioester) 1. Condensation of growing chain with activated acetate B ketocyl ACP synthase (KS) 2. Reduction of carbonyl to hydroxyl B ketoacyl ACP reductase (KR) 3. Dehydration of alcohol to transalkene B hydroxyacyl ACP dehydratase (DH) 4. Reduction of alkene to alkane enoyl ACP reductase (ER) Chain transfer/charging: malonyl/acetyl COA ACP transferase

Oxidation of odd numbered fatty acids such as propionyl-COA (formed from B-oxidation) requires

coenzyme B12, biotin

mineralcorticoids fxn

control electrolyte balance, reabsorption of Na+, Cl−, HCO3− from kidney

Two _____ (formed by 1 IPP and 1 geranyl pyrophosphate) join head to head to form phosphate-free squalene

farnesyl pyrophosphate (15C)

Phosphatidic acid ---> triacylglycerol

lipin removes 3-phosphate from phosphatidic acid to yield 1,2 diacylglycerol then the third carbon gets acetylated with a third fatty acid

Example of statin, found in fungi

lovastatin

Fatty acid anabolism Requires: _____ & ______ Requires: reducing power from _______ Takes place in:

Acetyl-CoA and malonyl- CoA NADPH Cytosol in animals, chloroplast in plants

Reaction catalyzed by Acyl-coenzyme A cholesterol acyl transferases (ACAT)

Acyl COA --> cholesteryl ester

Origin of glycerol-3-phosphate for TAG and phospholipid backbone

- Backbone of TAG & phospholipids: glycerol 3 phosphate comes from dihydroxyacetone phosphate (DHAP) from glycolysis, but some comes from glycerol - Glycolysis: glycerol 3 phosphate dehydrogenase - Glycerol: glycerol kinase

Explain the detailed reaction catalyzed by HMG-CoA reductase

- HMG-COA reductase is the rate limiting step of cholesterol synthesis - Starting with HMG-COA, 2 NADPH are needed to reduce HMG-COA into mevalonate (a 5 carbon product)

ACC is the rate-limiting step of fatty acid synthesis and it is active when it is phosphorylated. How is acetyl CoA carboxylase (ACC) regulated?

- Inhibited by palmitoyl-COA, glucagon, epinephrine (inhibited when energy is needed) - Activated by citrate - Regulated by covalent modification (glucagon and epinephrine phosphorylate ACC to inactive it)

Explain the detailed reaction catalyzed by HMG-CoA synthase

- Three acetyl COAs are condensed by thiolase to form acetoacetyl-COA - Acetoacetyl-COA is then condensed to HMG-COA via HMG-COA synthase (a 6 carbon product)

Adrenal gland-synthesized steroids:

- mineralcorticoids - glucocorticoids

Insulin stimulates tricylglycerol ______ and lack of insulin results in increased ____ & _____ & ____

-synthesis -lipolysis -fatty acid oxidation (ketones if oxaloacetate is depleted) - failure to synthesize FAs

Acetyl-COA carboxylase reaction occurs in two parts. Summarize the two parts.

1. BIOTIN CARBOXYLASE: Co2 binds to biotin, requires ATP, Co2 is activated by attachment to N in biotin 2. TRANSCARBOXYLASE: enzyme conformational change to carry carbamoyl to transcarboxylase site, Co2 attached to acetyl-coa and leaves active site

Characteristics of different lipoproteins based on sedimentation (density) in centrifuge, listed based on density smallest to largest:

1. Chylomicrons <1.006 2. VLDL 0.95-1.006 3. LDL1.006 <1.063 4. HDL 1.063 < 1.210

Glucagon binds to receptor, activates adenylate cyclase, which catalyzes coversion of ATP to cAMP, finally activating PKA. Which lipases are phosphorylated by PKA?

1. Hormone sensitive lipase (HSL) 2. adipocyte triacylglycerol lipase (ATGL) 3. monoacylglycerol lipase (MGL)

Know the steps in transport of fatty acids into mitochondria

1. acyl coa is conjugated to carnitine by carnitine acyltransferase I, gets shuttled inside the mitochondrial membrane 2. acyl carnitine is concerted to acyl COA by carnitine acyltransferase II located in the inner mitochondrial membrane 3. carnitine goes back to cytosol

Define the basic structure of cholesterol

27C Four rings

Squalene is a linear ___ carbon molecule

30

Define the basic structure of a squalene

30C

___ cycles of B-oxidation are required for catabolism of palmitic acid (16C). Therefore, ____ acetyl COA are formed ____ NADH are formed ____ FADH2 are formed

7 cycles 8 acetyl COA are formed 7 NADH are formed 7 FADH2 are formed

How many ATP are formed for B-oxidation of palmitic acid (C16)?

8 acetyl COA 7 NADH 7 FADH2 8 x 10 = 80 4(1.5+2.4) x 7 = 28 108 --> 106 bc not completely oxidized

Know the action of aspirin, ibuprofen on cyclooxygenase

Asprin (acetylsalicylate) = irreversible inhbiitor - acetylates Serine residue Ibuprofen/naproxen = competitive inhibitors

Why is linoleic acid important?

Because plants can desaturate beyond C9 unlike humans so certain fatty acids are essential. it is needed for hormone snthesis

Synthesis of phospholipids in eukaryotes repacles ___ instead of glycerol like in E.Coli

CMP

Reactions catalyzed by COX-1 and COX-2

COX-1: Synthesis of prostaglandings that regulate gastric mucin secretion COX-2: synthesis of prostaglandings that mediate pain, fever, inflamattion

NSAIDS like ibuprofen, aspirin, and acetominophen inhibts COX-__

COX-2

Role of statins

Competitive inhibitors of HMG COA Reductase (resemble mevalonate)

General 4 steps of B-oxidation

D,H,D,T 1. dehydrogenation 2. hydration 3. dehydrogenation 4. transfer

Explain step 3 of B-oxidation

Dehydrogenation of alcohol Substrate: L-β-Hydroxy-Acyl-COA Enzyme: β-hydrozyacyl-COA dehydrogenase w/ NAD cofactor Product: β-ketoacyl-COA

Explain step 1 of B-oxidation

Dehydrogenation of alkane to alkene Substrate: palmitoyl COA Enzyme: acyl COA dehydrogenase (AD) in inner mitochondrial membrane Product: trans-delta^2-enoyl COA trans double bond is formed

Know the enzyme and steps involved in synthesis of prostaglandins and thromboxanes

Enzyme: PGH2 synthase (cyclooxygenase/peroxidase) Step 1: PGH2 cyclooxygenase adds 2 O2 to form PGG2 Step 2: PGH2 peroxidase converts peroxide to alcohol to make PGH2

Fatty acid synthesis is catalyzed by fatty acid synthase (FAS). What are the features and structure of FAS? Growing chain is initially attached to enzyme via ____ linkage

Fxn: attache acetate unit (2C) from malonyl-coa to a growing chain then reduce it Features: uses NADPH as the e- donor, uses 2 enzyme bound -SH groups as activating groups Structure: Single polypeptide chain in vertebrates and fungi, leads to single product palmitate 16:0, C-15 and C-16 are from acetyl COA used to prime the reaction thioester

The rate limiting step in cholesterol synthesis is

HMG-COA Reductase (HMG-COA → mevalonate)

How cholesterol synthesis is regulated by Covalent modification ( enzymes involved, phosphorylation and dephosphorylation forms)

HMG-COA Reductase is most active when dephosphorylated - activated by insulin - inhibited by glucagon, epinephrine, AMP (amp kinase)

Rate limiting step of cholesterol synthesis is _____ and is a common target for cholesterol lowering drugs

HMG-COA reductase

Explain step 2 of B-oxidation

Hydration of alkene Substrate: trans-delta^2-enoyl COA Enzyme: enoyl-COA hydratase Product: L-β-Hydroxy-Acyl-COA

How cholesterol synthesis is regulated by Proteolytic degradation( how HMG-CoA becomes susceptible to proteolysis)

Insig (insulin induced gene protein) senses cholesterol levels and triggers ubiquitination of HMG COA reductas --> proteosome degradtion

One Acetyl-COA = ____ ATP

One Acetyl-COA = 10 ATP

One NADH = ____ ATP One FADH2 = ____ ATP Therefore, a total of _____ ATP are formed in one round of B-oxidation

One NADH = 2.5 ATP One FADH2 = 1.5 ATP Therefore, a total of 4 ATP are formed in one round of B-oxidation

Reaction catalyzed by Lecithin-Cholesterol Acyl Transferase (LCAT)

Phosphatidylcholine (lecithin) --> cholesteryl ester

Fatty acid catabolism ______ acetyl CoA Produces: reducing power (_____, ______) Takes place in:

Produces NADH, FADH2 Mitochondria

How fatty acid oxidation is inhibited during fatty acid synthesis?

Reciprocal regulation: malonyl COA inhibits fatty acid import into the mitochondria

List the requirements of the reaction for desaturation of fatty acids

Requirements: NADPH, b5, and cytochrome b5 reductase Enzyme: fatty acyl COA desaturase

Why is HDL called good cholesterol?

Reverse Cholesterol Transport by HDL Explains Why HDL Is Cardioprotective - HDL picks up cholesterol from nonliver tissues, including foam cells at growing plaques. - HDL carries cholesterol back to the liver.

Explain step 4 of B-oxidation

Transfer of fatty acid chain and release of acetyl coa Substrate: β-ketoacyl-COA Enzyme: acyl-COA acyltransferase (thiolase) Product: Acyl-COA (myristoyl-COA)

All carbons of cholesterol are derived from

acetyl COA

Each round of B-oxidation produces an ______ and shortens the chain by ____ chains

acetyl coa 2

Precursor for synthesis of cholesterol

acetyl coa (3)

The enzyme _____ carboxylates acetyl coa to form malonyl COA and it has three subunits.

acetyl coa carboxylase

Malonyl CoA is formed from _____ and _____

acetyl-CoA and bicarbonate (carboxylation of acetyl coa)

_____ serves as a shuttle in fatty acid synthesis

acyl carrier protein (ACP)

Small FAs are able to freely diffuse across mitochondrial membranes but larger FAs require _____ for transportation

acyl-carnitine/carnitine transporter

The serum protein ____ transports fatty acids since they are water insoluble

albumin

Fatty acid synthesis is AKA fatty acid ___bolism

anabolism

Precursor of eicosanoids

arachidonic acid (arachidonate)

Phosphatidic acid ---> phospholipid

attachment of head group (serine, choline, ethanolamine, etc)

Fatty acid oxidation = fatty acid ___bolism

catabolism

These hormones trigger mobilization of stored triacylglycerols via lipase activation

epinephrine & glucagon

Cholesterol synthesis occurs in

the liver, then exported as bile salts, biliary cholesterol, and cholesterol esters

Fats are degraded into ___ and ____. The second product listed enters glycolysis.

fatty acids and glycerol

Cause of familial hypercholesterolemia

genetic mutation in LDL receptor

Name some steroids formed from cholesterol

glucocorticoids, mineralocorticoids, progestogens, androgens, and estrogens

What is the source of Glycerol 3 phosphate (from DHAP) for fatty acid resterificatio?

glycolysis is inhibited during lipolysis which is stimulated by glucagon and epinephrine and adipose dont have glycerol kinase so cells make DHAP via glycerogenesis by converting pyruvate --> DHAP w/ glycerol 3 phosphate dhydrogenase

HMG-CoA is present

in the membrane of the endoplasmic reticulum

Oxidation of monounsaturated fatty acids require an additional enzyme:

isomerase

How cholesterol synthesis is regulated by transcription( role of SCAP and SREBPs)

low sterol = increased transcription /cholesterol synthesis SREBPs= sterol regulatory element binding proteins - when sterol is high, SCAP/SREBP stay in the ER - when sterol is low, complex is cleaved, regulatory domain moves to nucleus, and activates transcription of HMG COA reductase and LDL receptor

Which molecule serves as a donor of two carbon atoms in fatty acid synthesis

malonyl COA

Fatty acids are built in several passes, adding one acetate (two carbons) at a time. The acetate comes from activated malonate in the form of ______

malonyl-CoA (3C)

cholesteryl esters are more ____ than cholesterol

more hydrophobic & nonpolar

Fatty acids are ____ so they complex or carry less water than polysaccharides

nonpolar

Precursor of TAGs and phospholipids

phosphatidic acid

Synthesis of these three phospholipids constitute a salvage pathway

phosphatidylserine phosphatidylcholine phophatidylethanolamine

Phospholipid synthesis in E.Coli includes intermediates/products such as

phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, cardiolipin

Phospholipid synthesis in eukaryotes includes intermediates/products such as

phsophatidylenositol, cardiolipin

Gonad-synthesized steroids:

progesterone, androgens, estrogens

75% of free fatty acids (FFAs) released by lipolysis are _____ to form TAGs rather than be used for fuel

re-esterified, occurs in adipose tissue the 75% is constant under all conditions

glucocorticoid fxn

regulate gluconeogenesis, reduce inflammation

Squalene is formed from condensation of

six activated isoprene units (two farnesyl pyrophosphates join head to head)

Where are dietary fatty acids absorbed?

small intestine