Biochem II Exam IV (Part 1)

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What are the steps of triacylglycerol synthesis from phosphatidate?

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What are the steps of triacylglycerol synthesis from phosphatidate?

phosphatidate, phosphatidic acid phosphatase, DAG, diglyceride acyltransferase, triacylglycerol

<p>phosphatidate, phosphatidic acid phosphatase, DAG, diglyceride acyltransferase, triacylglycerol</p>
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What is the initial product of sphingolipid synthesis?

ceramide

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What are the steps in the synthesis of ceramide?

palmitoyl CoA + serine, (bunch of rxns), dihydroceramide, ceramide

<p>palmitoyl CoA + serine, (bunch of rxns), dihydroceramide, ceramide</p>
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Which lipids function as second messengers in a variety of signal pathway?

ceramide, sphingosine, sphingosine 1-phosphate

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What is the key regulatory enzyme in lipid metabolism?

Phosphatidic Acid Phosphatase

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Phosphatidic acid phosphatase catalyzes the conversion of…

phosphatidate to DAG

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In lipid metabolism, different lipids are synthesized depending on…

whether phosphatidic acid phosphatase is active or not

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Loss of phosphatase activity in mice results in…

loss of body fat and the development of insulin resistance

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What is the starting compound of cholesterol synthesis?

acetyl CoA

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What are the 3 stages of cholesterol synthesis?

  1. The synthesis of Isopentenyl pyrophosphate from mevalonate (cytoplasm)

  2. Condensing of 6 molecules of isopentyl pyrophosphate to form squalene (ER)

  3. The cyclization of squalene which is then converted into cholesterol (ER)

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cytochrome P450 monooxygenases also functions _______ foreign substances

detoxify

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Class of membrane-anchored enzymes that use heme as a prosthetic group and catalyze the hydroxylation of cholesterol

cytochrome P450 monooxygenases

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What are the fates of the O2 substrate used in cytochrome P450 monooxygenases?

one is used to yield the hydroxylated product and the other is reduced to form H2O

<p>one is used to yield the hydroxylated product and the other is reduced to form H2O</p>
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SREBP stands for…

sterol regulatory element binding protein

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When cholesterol levels fall SCAP…

escorts SREBP to the Golgi complex where it is proteolytically processed and activated. There, the activated SREBP moves to the nucleus to stimulate reductase mRNA synthesis. (transcription factor)

<p>escorts SREBP to the Golgi complex where it is proteolytically processed and activated. There, the activated SREBP moves to the nucleus to stimulate reductase mRNA synthesis. (transcription factor)</p>
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When cholesterol levels are adequate, SCAP binds to cholesterol, which causes a structural change in SCAP that allows SCAP to bind to…

Insig (insulin induced gene)

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What prevents the HMG CoA reductase gene from NOT being transcribed?

The interaction between SCAP and Insig. It traps SCAP and SREBP in the ER mem

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Additional regulatory strategies for cholesterol biosynthesis:

  1. Rate of translation of reductase mRNA being inhibited by nonsterol metabolites of mevalonate.

  2. Increase in cholesterol resulting in the proteolytic degradation of the reductase. (leads to the reductase being tagged for degradation by ubiquitin/proteasome)

  3. Phosphorylation of reductase by AMP-activated protein kinase inactivates enzyme (allows cholesterol synthesis to cease when the ATP level is low)

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Cholesterol and triacylglycerols are transported in the blood in the form of …

lipoprotein particles

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Cholesterol and triacylglycerols serve to _______ lipids and to direct ____________________

solubilize; lipoprotein particles to specific targets

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major transporter of cholesterol in the blood to peripheral tissues

Low-density lipoprotein, LDL

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carries cholesterol released from dying cells and membranes undergoing turnover and brings it back to the liver for excretion (reverse cholesteroltransport)

High-density lipoprotein, HDL

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The 3 steps of receptor-mediated endocytosis:

  1. LDL binds to LDL receptor

  2. LDL-receptor complex is internalizedendocytosis.

  3. LDL is hydrolyzed in lysosomes, and the LDL receptor is returned to the cell surface to bind another LDL particle.

<ol><li><p>LDL binds to LDL receptor</p></li><li><p>LDL-receptor complex is internalizedendocytosis.</p></li><li><p>LDL is hydrolyzed in lysosomes, and the LDL receptor is returned to the cell surface to bind another LDL particle.</p></li></ol>
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In the process of reverse cholesterol transport, HDL removes…

cholesterol from macrophages and returns it to the liver for use as bile salts or excretion

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Competitive Inhibitor of HMG-CoA reductase

Lovastatin

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Bile salts are synthesized in the _____ and stored in the _________ until secreted into the ________________

liver; gallbladder; small intestines

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Cholesterol is a precursor to…

steroid hormones, vitamin D, and bile salts

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detergents that render dietary lipids more accessible (due to having both a polar and nonpolar region) for digestion by lipases and thus facilitate the formation of fatty acid products

bile salts

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What are the 5 major classes of steroid hormones?

progesterone, testosterone, estradiol, cortisol, aldosterone

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prepares the uterus for implantation and supports pregnancy

progesterone (a progestogen)

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promotes development of male sexual behavior and lean muscle mass

testosterone (an androgen)

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promotes the development of female sex characteristics

estradiol (an estrogen)

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stimulates glucose and glycogen synthesis and inhibits the inflammatory response

cortisol (a glucocorticoid)

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regulates salt balance and the volume and pressure of blood

aldosterone (a mineralocorticoid)

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a metabolite of testosterone, supports the embryonic development of the male phenotype

dihydrotestosterone

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All of the steroid hormones operate in a similar fashion, in that they…

bind to and activate receptor molecules that subsequently regulate gene expression

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Vitamin D is formed from cholesterol by the ___________ of UV-light

ring-splitting

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In what cellular location does the synthesis of phosphatidate occur?

ER and outer mitochondrial membrane

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Primary site of triacylglycerol synthesis

Liver

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Phospholipid synthesis requires the combination of a(n) ________ with an _______. As in most anabolic reactions, one of the components must be activated. Which will depend on the source of the reactants.

CDP-diacylglycerol ; alcohol

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The degradation of PHE requires oxygen. Where does the oxygen come from?

molecular oxygen

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Amino transferases require PLP for activity. Which of the following is true concerning PLP?

a) The mechanism is very much like a protease breaking a peptide bond.

b) PLP donates high energy electrons to the reaction

c) PLP is covalently attached to the substrate by a Schiff-base linkage

d) PLP is attracted to the substrate by hydrophobic interactions

e) none of the choices

c

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The carbon skeletons of ___ directly enter metabloism at the level of pyruvate.

a) TYR and TRP

b) VAL and ILE

c) ALA and SER

d) THR and GLY

e) none of the choices

c

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What is the activated diacylglycerol in the synthesis of some phospholipids?

cytidine diphosphodiacylglycerol (CDP-diacylglycerol)

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The reaction of phosphatidate with cytidine triphosphate (CTP) to form the activated diacylglycerol (CDP-diacylglycerol) is driven forward by what?

by the hydrolysis of pyrophosphate.

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The hydroxyl group on cholesterol and the subsequent hydroxyl groups added in the synthesis of steroid hormones are derived from…

a) water

b) hydroxide

c) carbon dioxide

d) molecular oxygen

e) none of the choices

d

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In the synthesis of TAG and phospholipids, fatty acids are first attached to glycerol 3-phosphate . Which molecule is a source of glycerol 3-phosphate?

a) phosphorylation of glycerol

b) pyruvate

c) acetyl CoA

d) malonyl CoA

e) none of the choices

a

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The activated phosphatidyl unit (CDP-DAG) reacts with the hydroxyl group of an alcohol to form a phosphodiester linkage. If the alcohol is inositol, the products are __________ and ________

phosphatidylinositol ; cytidine monophosphate (CMP)

<p>phosphatidylinositol ; cytidine monophosphate (CMP)</p>
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phosphatidylinositol 4,5-bisphosphate is the precursor of what two intracellular messengers?

DAG and inositol 1,4,5-trisphosphate

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If the alcohol CDP-DAG reacts with is phosphatidylglycerol what are the products?

diphosphatidylglycerol (cardiolipin) ; CMP

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In eukaryotes, cardiolipin is synthesized in the __________ and is located exclusively in the ____________.

mitochondria ; inner mitochondrial membranes

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Plays an important role in the organization of the protein components of oxidative phosphorylation

cardiolipin

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required for the full activity of cytochrome c oxidase

cardiolipin

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another word for cardiolipin

diphosphatidylglycerol

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<p>Identify the compound</p>
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<p>Identify the compound</p>

Identify the compound

<p>Identify the compound</p>

Cardiolipin

<p>Cardiolipin</p>
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Phosphatidylinositol is unusual in that it…….. Stearic acid usually occupies the C-1 position and arachidonic acid the C-2 position.

has a nearly fixed fatty acid composition

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most common phospholipid in mammals comprising approximately 50% of the membrane mass

phosphatidylcholine

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this compound is the starting point for the formation of sphingomyelin and gangliosides.

ceramide

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the most complex sphingolipids

gangliosides

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induces apoptosis

ceramide

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What are the signal molecules that stimulate phosphatidic acid phosphatase?

CDP-DAG, phosphatidylinositol, and cardiolipin

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What are the signal molecules that inhibit phosphatidic acid phosphatase?

sphingosine and dihydrosphingosine

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When PAP is ___________it resides in the cytoplasm

phosphorylated

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When PAP is ___________it resides in the endoplasmic reticulum

dephosphorylated

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modulates the fluidity of animal cell membranes

cholesterol

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the committed step in cholesterol formation

the synthesis of mevalonate

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The synthesis of cholesterol involves the condensation of C5 units from isopentyl pyrophosphate . Which statement best summarizes the sequence of condensation that produce cholesterol?

a) Three C5 units are condensed to form a C15 unit followed by two C15 units combining to form a C30 unit that is cyclized and has carbons removed to make cholesterol (C27)

b) Nine C5 units combine together and then C3 units are removed until cholesterol (C27) is formed

c)Six C5 units are combined sequentially to make a C30 molecule that has 3C removed before it is cyclized into cholesterol (C27)

d) Two C5 units are combined to make C10. Three of the C10 units combined to make a C30 which is cyclized to form cholesterol

e) none of the above

a

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<p>Explain each step in the picture</p>
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<p>Explain each step in the picture</p>

Explain each step in the picture

<p>Explain each step in the picture</p>

The SREBP pathway. SREBP resides in the endoplasmic reticulum (ER), where it is bound to SCAP by its regulatory (Reg) domain. When cholesterol levels fall, SCAP and SREBP move to the Golgi complex, where SREBP undergoes successive proteolytic cleavages by a serine protease and a metalloprotease. The released DNA-binding domain moves to the nucleus to alter gene expression.

<p>The SREBP pathway. SREBP resides in the endoplasmic reticulum (ER), where it is bound to SCAP by its regulatory (Reg) domain. When cholesterol levels fall, SCAP and SREBP move to the Golgi complex, where SREBP undergoes successive proteolytic cleavages by a serine protease and a metalloprotease. The released DNA-binding domain moves to the nucleus to alter gene expression.</p>
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<p>Explain what is occuring in the picture</p>
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<p>Explain what is occuring in the picture</p>

Explain what is occuring in the picture

<p>Explain what is occuring in the picture</p>

In the presence of sterols, a subclass of Insig associated with ubiquitinating enzymes binds HMG-CoA reductase. This interaction results in the ubiquitination of the enzyme. This modification and the presence of geranylgeraniol results in extraction of the enzyme from the membrane and degradation by the proteasome.

<p>In the presence of sterols, a subclass of Insig associated with ubiquitinating enzymes binds HMG-CoA reductase. This interaction results in the ubiquitination of the enzyme. This modification and the presence of geranylgeraniol results in extraction of the enzyme from the membrane and degradation by the proteasome.</p>
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Triacylglycerols, cholesterol, and other lipids obtained from the diet are carried away from the intestine in the form of large …

chylomicrons

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<p>Identify the structure and the color-coded regions</p>
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<p>Identify the structure and the color-coded regions</p>

Identify the structure and the color-coded regions

<p>Identify the structure and the color-coded regions</p>

low-density lipoprotein (LDL)

<p>low-density lipoprotein (LDL)</p>
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the polar derivatives of cholesterol

bile salts

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major sites of synthesis for progestogens

corpus luteum

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major sites of synthesis for androgens

testes

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major sites of synthesis for estrogens

ovaries

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major sites of synthesis for glucocorticoids and mineralocorticoids

adrenal cortex

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Give examples of the wide variety of compounds formed from the C5 isopentenyl pyrophosphate

terpenes, natural rubber, carotenoids, and the side chains of": CoQ, chlorophyll, and Vit K

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an isoprenoid

farnesene

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All glycerol-containing phospholipids are derived from:

a) Ceramide

b) Ganglioside

c) Mevalonate

d) Phosphatidate

d

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Sphingolipids are synthesized from:

a) Ceramide

b) Phosphatidylserine

c) Diacylglycerol

d) Isoprene

a

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The synthesis of phosphatidylcholine from phosphatidylethanolamine requires:

a) Tetrahydrofolate

b) Glycine

c) Choline

d) S-Adenosylmethionine

c

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Cholesterol is synthesized entirely from:

a) Oxaloacetate

b) Glycerol 3-phosphate

c) Acetyl CoA

d) Serine

c

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Bile salts are synthesized from:

a) Cholesterol

b) Prostaglandin

c) Triacylglycerol

d) Ceramide

a

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