Exam #3: (32-38)

Question 1

Describe the LDL endocytosis process

Answer 1

1. ) LDL binds receptor
2. ) Vesicle containing bound LDL loses its clathrin and FUSES with other similar vesicles, forming larger vesicles called ENDOSOMES.
3. ) The pH of the endosome FALLS (due to proton-pumping activity of endosomal ATPase), which allows for separation of the LDL from its receptor. Receptors migrate to one side of the endosome, and LDLs stay free in the lumen of the vesicle (this structure is called the Compartment for Uncoupling of Receptor and Ligand (CURL).
4. ) Receptors are recycled, lipoprotein remnants transeffered to lysosomes and degraded by lysosomal acid hydrolases, releaseing free cholesterol, amino acids, FA, and phospholipids. These can be utilized in the cell.
   p. 427

Question 2

What does Glutamine Synthetase do?

Answer 2

• Removes excess ammonia (NH4+) by adding it to glutamate to form GLUTAMINE.
• It then travels to the liver and kidney where NH4+ is removed by GLUTAMINASE to reform Glutamate.

Question 3

What is nitrogen balance?

Answer 3

The difference between dietary intake of nitrogen (mainly protein) and its excretion (as urea and other waste products)

Question 4

How are dietary proteins digested (3)? Describe

Answer 4

1. ) Stomach: HCL (pH 2-3) via parietal cells, and Pepsinogen–pepsin (mainly bulky, hydrophobic amino acids)
2. ) Pancreatic enzymes: Endo and exopeptidases
3. ) Intestines: Enteropeptidase activates zymogens –> Aminopeptidases: exopeptidase that cleaves N-terminus, making a free amino acid and smaller peptide

Question 5

1. ) Under low-energy conditions, what will happen concerning amino acids?
2. ) What stimulates this process?

Answer 5

1. ) They will be deaminated to alpha-keto acids (alpha-ketoglutarate) in order to feed the TCA.
2. ) ADP (or AMP) and GDP

Question 6

• What are the two sources of nitrogen for ammonia?

- What else is needed?

Answer 6

• Ammonia as CARBAMOYL PHOSPHATE, and ASPARTATE
• 4 ATP
• 5 enzymes

Question 7

1. ) Which hormone(s) stimulate the production of testosterone and estrogen? Where from?
2. ) Via which type of pathway do they operate?

Answer 7

1. ) Leutinizing Hormone (LH) and Follicle-stimulating Hormone (FSH). Both from the anterior pituitary.
2. ) Gs signaling pathway

Question 8

Generally speaking, by what mechanism do ALL statins function?

Answer 8

They are all COMPETITIVE INHIBITORS of HMG-CoA REDUCTASE = Drop in cholesterol synthesis in the liver.

Question 9

What is the medical term for chronic endothelial injury?

Answer 9

Atherosclerosis

Question 10

What are the products of LDL metabolism (3)?

Answer 10

1. ) Cholesterol
2. ) Fatty acids
3. ) Amino acids

Question 11

What is the progression of intermediates in the synthesis of steroid hormones (corticosteroids, sex steroids, progesterone)? Give the subclasses of all.

Answer 11

Cholesterol –> Progesterone
Cholesterol –> Progesterone –> Corticosteroids (glucocorticoids and mineralcorticoids)
Cholesterol –> Progesterone –> Sex Steroid (androgens and estrogens.

Question 12

1. ) What is formed by transferring an amino group from alanine to alpha-ketoglutarate (2)?
2. ) What mediates this reaction?

Answer 12

1.)Alpha-ketoglutarate –> Glutamate (glutamic acid)
Alanine –> Pyruvic acid, an alpha-keto acid
2.) Alanine Transaminase (ALT) and Vitamin B6

Question 13

1. ) What are the effects of progestins (2)?

2. ) What are the primary progestins (2)?

Answer 13

1. ) Nidation (implantation), maintenance of pregnancy

2. ) Progesterone, 17-alpha-hydroxy-progesterone

Question 14

Describe LCAT deficiency

1. ) Causes
2. ) Clinical presentation

Answer 14

1. ) An inability to esterify cholesterol, thus, increased total free cholesterol in tissues.
2. ) Diffuse corneal opacities (fish-eye disease…partial LCAT deficiency), proteinuria with renal failure, hemolytic anemia (increased cholesterol in RBCs = pts may succumb to renal failure).

Question 15

1. ) What is the clinical presentation for HYPERAMMONEMIA (5)?
2. ) Glutamine and astrocytes?
3. ) Ammonia plasma levels?

Answer 15

1. ) Tremors, lethargy, slurring speech, vomiting, blurred vision
2. ) Glutamine ALWAYS elevated, astrocyte swelling,
3. ) ammonia plasma levels 2-3x higher in mild cases, 10x higher in severe

Question 16

What does SYNTHETASE imply?

Answer 16

Use of energy in the form of ATP

Question 17

After release from the liver, VLDL receives _____ and _____ from ______.

Answer 17

VLDL receives C-II and E from HDL.

Question 18

Explain Glutamate and Ischemia-induced brain damage

Answer 18

Last 5 min of Lecture 37

Question 19

Describe the apoproteins associated with chylomicrons (3):

1. ) 4 things: Synthesis location, modifications, method of transport
2. ) 1 thing: Function
3. ) 2 things: Function, pathology

Answer 19

1. ) ApoB 48: Unique to chylomicrons, synthesized in intestines, glycosylated, MTP loads lipids onto ApoB48 in SMOOTH ER.
2. ) ApoCII: Activates lipoprotein lipase
3. ) ApoE3: Needed for recognition by receptor. Presence of ApoE4 isozyme predisposing genetic risk factor for late-onset ALZHEIMER’S.

Question 20

Where is the main site for ammonia detox?

Answer 20

Liver…if you want to LIVE, you need to make UREA in the LIVER

Question 21

How does LDL synthesis regulation work on the nuclear level under HIGH [cholesterol], i.e. –> 1.) What controls the transcription the enzymes needed for synthesis, and 2.) How does it work (2 steps)?

Answer 21

1.) Regulated by Insulin-Induced Gene Products (INSIG): An ER membrane protein.

2. ) Under high [cholesterol] conditions:
   a. ) INSIG binds SREBP-SCAP and prevents its movement to the Golgi by anchoring it in the ER.
   b. )This prevents movement to the NUCLEUS = NO GENE ACTIVATION OF HMG-CoA REDUCTASE or LDLR GENE.

Question 22

Before leaving the liver, VLDL is tagged with _______, (which is related to _____…how?)

Answer 22

Tagged with ApoB100 –> which is related to Apo-B48 (i.e. translated from the same gene), except Apo-B100 is 100% translated without a STOP CODON in the middle.

Question 23

Describe Hyperlipidemia Type 4: VLDL, aka ______.

1. ) Caused by?
2. ) What is it characterized by?
3. ) Associated risks?

Answer 23

AKA: Hypertriglyeridemia (>200 mg/dL)

1. ) Overproduction of VLDL, decreased clearance of VLDL, increased [ID] (VLDL remnant).
2. ) Characterized by: High blood triglyceride levels and obesity, usually with mild DM.
3. ) Associated with an increased risk for coronary atherosclerosis.

Question 24

1. ) Which is present in greater concentration in circulation, glucocorticoids or mineralcorticoids?
2. ) How do tissues avoid responding to the one with a greater concentration (how do they maintain selectivity)?

Answer 24

1. ) Glucocorticoids
2. ) They metabolize the higher concentration to an inactive compound, e.g. Cortisol to cortisone in glucocorticoids (carbenoxolone prohibits this effect)

Question 25

Describe Type 2a Hyperlipidemia, aka ______ 1. ) Genetics? 2. ) Blood test presentation 3. ) Clinical presentation

Answer 25

AKA Familial Hypercholesterolemia: Deficiency in functioning LDL receptors. 1. ) Autosomal dominant 2. ) Elevated LDL and plasma cholesterol (500-800mg/dL cholesterol) 3. ) Premature atherosclerosis, low tri, xanthomas (lipid deposits) on elbows, knees, ear lobes, around the eyes (xanthelasma), Achilles tendons.

Question 26

How are branched-chain AA metabolized?

Answer 26

In muscle, NOT BY THE LIVER

Question 27

Describe the function and composition of the four lipoproteins

Answer 27

1. ) Chylomicrons: Triglycerides with some cholesterol. Carry dietary lipids from intestine, to lymph, into the blood stream, and to peripheral tissues. 2. ) VLDL: Carries hepatic lipids (TG, cholesterol, etc.) from liver to blood. 3. ) LDL: Carries mainly hepatic cholesterol (reason for just low density) to peripheral tissues. 4. ) HDL: "Good cholesterol." Takes cholesterol out of tissues to be stored, or re-synthesized into bile acids, steroids, etc.

Question 28

What mediates transamination in aspartate? cofactors?

Answer 28

Aspartate Transaminase (AST)

Question 29

1. ) What is formed by transferring an amino group from aspartic acid (aspartate) to alpha-ketoglutarate (2)? 2. ) What mediates this reaction?

Answer 29

1.) Alpha-ketoglutarate --> Glutamic acid (glutamate) Aspartic acid (aspartate) --> Oxaloacetate (OAA), *an alpha-keto acid* 2.) Aspartate Transaminase (AST) and Vitamin B6

Question 30

What is the most common genetically acquired hyperammonemia?

Answer 30

Ornithine transcarbamoylase (x-linked)

Question 31

What are the main sources for amino acids (3)?

Answer 31

1. ) Dietary protein 2. ) Body protein (muscle) 3. ) Metabolic intermediates, e.g. alpha-ketoglutarate for biosynthesis of NON-ESSENTIAL AAs.

Question 32

Once the steroid diffuses through the membrane into a cell, where does it bind its receptor?

Answer 32

Either in the cytoplasm or on the nucleus. Either way, it must get to nucleus to exert its effect.

Question 33

As VLDL passes through the capillaries, _____ is activated by ______, which hydrolyzes the TG which are released as free FA, and subsequently delivered to peripheral tissues.

Answer 33

Lipoprotein lipase is activated by C-II.

Question 34

In a VERY general sense, what occurs under low [cholesterol] conditions (2)?

Answer 34

There is an increase in CHOLESTEROL SYNTHESIS and LDL RECEPTORS

Question 35

How does cholesterol released from peripheral cells stay inside of the HDL? What does this? What is HDL called afterwards?

Answer 35

- Cholesterol is esterified (hydroxyl group becomes a fatty acid), making it more HYDROPHOBIC. - Cholesterol is esterified by ENZYME LECITHIN-CHOLESTEROL ACYLTRANSFERASE (LCAT). - It is called HDL2 afterwards (once it has cholesterol ester inside)

Question 36

a. ) List the effects mineralcorticoids elicit in response to stress (3), and what stimulates their production (2). b. ) What are the TWO main mineralcorticoids?

Answer 36

a.) *Mineralcorticoid production stimulated by ACTH and Angiotensin II* Stress responses: 1.) Increased Na+ retention (hypertension) 2.) Increased water retention 3.) Increased Na+ absorption (low salt fluid) b.) Aldosterone, Deoxycorticosterone

Question 37

1. ) What is plaque? 2. ) What causes it? 3. ) What combats it (3)?

Answer 37

1. ) Cholesterol deposits along the vascular system (especially in the arteries. 2. ) Oxidized cholesterol by Reactive Oxygen Species (ROS), smoking, etc. 3. ) Anti-oxidants, e.g. Vitamin E, ascorbic acid, ß-carotene, etc.

Question 38

What is a long half-life? Which has the longest?

Answer 38

*Months or years* | Structural proteins have the longest half-lives, e.g. collagen (approximately 1 year).

Question 39

Describe the 1.) structure and 2.) effects of Lipoprotein(a), aka Lp(a)

Answer 39

1. ) Consists of an LDL-like particle and the specific apo(a) protein. Contains a "kringle" protein motif (looks like a Danish pretzel). 2. ) Major risk factor for cardiovascular disease and plaque formation. High degree of homology to plasminogen (prevents clot busting).

Question 40

Amino acid pool is in a ______

Answer 40

Steady state

Question 41

One mole of urea gets rid of HOW MUCH AMMONIA?

Answer 41

One urea gets rid of TWO MOLES OF NITROGEN. | approx. 20:30 Lecture 38

Question 42

What causes fatty liver (aka ______)? In what populations is it found?

Answer 42

Fatty liver (aka HEPATIC STEATOSIS): Caused by an imbalance between TRIGLYCERIDE SYNTHESIS and VLDL SECRETION. It is common among the obese, insulin dependent diabetes mellitus (IDDM), and alcoholics.

Question 43

____ and _____ are released following liver poisoning.

Answer 43

ALT and Bilirubin

Question 44

What is Hartnup Disorder?

Answer 44

Cannot absorb nonpolar amino acids, e.g. Trp (MORE?) Trp used for synthesis of SEROTONIN, MELATONIN, and NIACIN.

Question 45

1. ) What are the effects of estrogens (5)? | 2. ) What are the primary estrogens (3)?

Answer 45

1. ) They promote...Feminization and ESTRUS CYCLE. They INCREASE fat stores and HDL. They also DECREASE testosterone production in MALES. 2. ) Estradiol, estrone, estriol

Question 46

What are the sources of endocytosed cholesterol (3)?

Answer 46

1. ) Chylomicron remnant 2. ) IDL (VLDL remnant) 3. ) LDL

Question 47

What AA has the highest concentration in the blood? | Second highest?

Answer 47

Highest: Glutamine Second: Alanine

Question 48

The stability and vulnerability of lipid-rich plaques are determined by what? What is it composed of?

Answer 48

The overlying FIBROMUSCULAR CAP, composed of SMOOTH MUSCLE CELLS and EXTRACELLULAR MATRIX.

Question 49

A.) Concerning the deamination of D-AMINO ACIDS, what is the: 1.) enzyme 2.) cofactor 3.) products B.) What amino acid is this reaction mainly used for?

Answer 49

A.) 1. ) D-Amino Acid Oxidase (DAO) --> peroxisomal enzyme 2. ) FAD 3. ) Produces: Alpha-keto acids, NH3 (ammonia), H2O2 (peroxide) B.) D-Serine

Question 50

The triglycerides in VLDL are bound to _________.

Answer 50

Heparin sulfate proteoglycan

Question 51

What causes hyperammonemic encephalopathy?

Answer 51

Cytotoxic brain swelling due to ASTROCYTE SWELLING

Question 52

1. ) Describe the Ub-proteasome method for protein degradation 2. ) How does it work? Energy requirement? When (pre or post-translational)

Answer 52

1.) Ubiquitin-proteasome (UPS): Endogenous proteins that mark a protein with ubiquitin, which then tells it to be sent to proteasome for degradation. *Nuclear proteins are degraded by a Nuclear Proteasome* 2. ) Ub attaches to amino group on Lys *via the C-terminal Gly on Ub* - Requires ATP - Occurs post-translationally

Question 53

Deficiency in which enzyme would inhibit formation of cortisol and aldosterone, cause ambiguous genitalia, and cause accumulation of 11-deoxycorticosterone (11-DOC)

Answer 53

11ß-Hydroxylase Deficiency

Question 54

Chylomicrons are assembled in the _______. With what?

Answer 54

In the ER of the intestines, with TAG, cholesterol esters, phospholipids.

Question 55

1. ) Corticosteroid hormone receptors are found in the ________. 2. ) What keeps it there? 3. ) What allows it to move to its final destination?

Answer 55

1. ) Cytosol 2. ) Chaperone or Heat Shock Proteins (HSPs) 3. ) Binding to the hormone, after which it RELEASES the HSP and the complex migrates to the nucleus.

Question 56

1. ) Deficiency in which enzyme would produce diminished urination, hypotension, ambiguous genitalia, hyperpigmented gonads, increased 17alpha-hydroxyprogesterone, and increased Androstenedione? 2. ) Which hormones are inhibited?

Answer 56

1. ) 21-hydroxylase | 2. ) Aldosterone and cortisol

Question 57

What are the consequences of CARBAMOYL PHOSPHATE SYNTHETASE (CPS, 1st enzyme) and/or ORNITHINE TRANSCARBAMYLASE (OTC, 2nd enzyme) deficiency? What do the blood levels in these deficienies reveal?

Answer 57

Blood citrulline levels are very low or absent...If LOW citrulline and HIGH ammonia, DEFICIENCY IS RIGHT AT THE BEGINNING!

Question 58

1. ) What are the two major functions of apoproteins in lipoproteins? 2. ) Where are apoproteins synthesized?

Answer 58

1. ) Provides recognition sites for cell-surface receptors, activates enzyme activity. 2. ) Most synthesized in the liver, some in the intestine

Question 59

HDL (ApoA-1) takes up _______ (its main purpose) from ________ and _____

Answer 59

HDL takes up UNESTERIFIED CHOLESTEROL (HDL3) from cell membranes and peripheral tissue cells.

Question 60

The absence of which enzyme inhibits the synthesis of corticosteroids or sex steroids

Answer 60

3ß-Hydroxysteroid Dehydrogenase (3ß-HSD)

Question 61

What deficiency does accumulation of alanine, and finally very high levels of ammonia indicate?

Answer 61

N-acetylglutamate synthetase (NAGS)

Question 62

1. ) When is the nitrogen balance negative? | 2. ) When is the nitrogen balance positive?

Answer 62

1. ) Fasting, fever, burns, wasting diseases | 2. ) Growth, tissue repair, pregnancy, post-starvation

Question 63

Describe the function of CETP (cholesterol ester transfer protein). What is the result of their action?

Answer 63

CETP in plasma transfers cholesterol esters from HDL2 (?) to VLDL, while triglycerides and phospholipids are transferred to HDL. The result is that VLDL contains more cholesterol ester, and less TAG. This changes the density of VLDL.

Question 64

What is the MAJOR regulatory step in the urea cycle? a. ) What is the energy requirement? b. ) What compound is necessary for regulation? c. ) What enzyme is needed? d. ) Where does this reaction occur?

Answer 64

Reaction #1: Carbamoyl Phosphate Synthetase – I(CPSI) a. ) 2 ATP b. ) N-acetylglutamate c. ) N-Acetylglutamate Synthetase d. ) Mitochondria

Question 65

1. ) Deficiency of which enzyme inhibits synthesis of cortisol and sex steroids. 2. ) What would patients present with (5)? 3. ) What are the general effects?

Answer 65

1. ) 17alpha-Hydroxylase 2. ) Infantile genitalia, high BP, low cortisol, inadequate response of cortisol to ACTH, high serum progesterone. 3. ) Blocks production of sex hormones (ambiguous genitalia in men), reduced aldosterone (but high BP).

Question 66

What is the release of ammonia used for in the following locations? 1. ) Liver 2. ) Kidney 3. ) Intestines

Answer 66

1. ) Urea synthesis 2. ) Acid-base balance 3. ) Added to PORTAL SYSTEM...[NH3] in portal vein is 10x greater than anywhere else in the body

Question 67

1. ) What is the name for disorders of steroid biosynthesis? 2. ) Name them (4) 3. ) What will their effect be?

Answer 67

1. ) Congenital Adrenal Hyperplasia (CAH) 2. ) a. ) 3ß-OH steroid dehydrogenase deficiency b. ) 17-Hydroxylase deficiency c. ) 21-hydroxylase deficiency d. ) 11ß-Hydroxylase deficiency 3.) Decrease in cortisol production = Overproduction of ACTH

Question 68

ALT is relatively specific for _______, and thus is a good diagnostic for _______.

Answer 68

- Relatively specific for LIVER INJURY. | - A good diagnostic for HEPATITIS

Question 69

As blood w/ chylomicrons travel through the capillaries, free fatty acids are delivered to tissue as a result of activation of ________ on the capillary walls recognizing the ________.

Answer 69

As a result of LIPOPROTEIN LIPASE recognizing the C-II RECEPTOR on the chylomicrons.

Question 70

What are some symptoms of Cushing's Syndrome? Caused by?

Answer 70

``` Moon face (fat face), Hyperglycemia, thin skin. -Most caused by adrenal tumor....or overuse of steroids, e.g. Prednisone ```

Question 71

What are the two most important AA in the blood

Answer 71

Alanine and glutamine

Question 72

What is a lipoprotein? Describe the constituents of a lipoprotein (core and outer shell)

Answer 72

Lipoprotein: Complexes of lipids and specific proteins (Lipids + Apoprotein) - Neutral lipid core: Triacylglycerides and cholesterol esters. - Outer shell: Apoprotein (amphipathic), phospholipids (phosphate facing outward), or non-esterified cholesterol (with its cholesterol facing outward).

Question 73

What are the three regions of nuclear receptor proteins? Which region is most homologous across the various types?

Answer 73

1. ) Variable region 2. ) DNA binding domain 3. ) Hormone-binding domain * The DNA binding domain has the highest degree of homology*

Question 74

_______ is needed on LDL for receptor recognition.

Answer 74

ApoB-100

Question 75

Explain the Glucose-Alanine cycle (3 steps)

Answer 75

1. ) Muscle uses protein and creates ammonia which it transfers onto pyruvate --> pyruvate becomes ALANINE. 2. ) Liver then picks up alanine, removes the amino group from alanine (becomes PYRUVATE) and puts the amino group onto alpha-ketoglutarate (which then becomes glutamate) 3. ) Glutamate releases the amino group via DEAMINATION and sends it to the UREA CYCLE.

Question 76

What disorders cause over/underproduction of corticosteroids (3)?

Answer 76

1. ) Cushing Syndrome – Overproduction of CORTISOL (glucocorticoid) 2. ) Addison's Disease – Underproduction of CORTISOL (glucocorticoid) and ALDOSTERONE (mineralcorticoid) 3. ) Conn's Disease – Overproduction of ALDOSTERONE (mineralcorticoid)

Question 77

Give the normal ranges for LFTs

Answer 77

AST: 10 - 34 IU/L ALT: 8 - 37 IU/L

Question 78

1. ) [HDL2] _________ to the incidence of coronary atherosclerosis, thus.... 2. ) _____ HDL cholesterol puts you at higher risk for heart disease.

Answer 78

1. ) Inversely related. | 2. ) LOW HDL

Question 79

1. ) Give mnemonic for the ESSENTIAL AMINO ACIDS? | 2. ) What does essential mean?

Answer 79

``` 1.) PVT TIM HALL always TRies to ARGue Phe Val Thr Trp Ile Met His (may not be essential in adults) Arg (not essential in adults) Leu (strictly ketogenic) Lys (strictly ketogenic) ```

Question 80

What are symptoms of Conn's syndrome? Treatments?

Answer 80

Hypervolemia = Increased: Blood volume (increased Na+), BP, Urine K+ and H+ = Metabolic acidosis -Treated by: Unilateral adrenalectomy or ALDOSTERONE BLOCKERS

Question 81

What are the two major functions of lipoproteins?

Answer 81

1. ) Transport lipids in SERUM | 2. ) Keep lipids soluble in SERUM

Question 82

1. ) Which hormone(s) regulate the synthesis of ALL adrenal steroid hormones, and where do they come from? 2. ) Via which type of pathway do they operate?

Answer 82

1. ) *Adrenocorticotropic Hormone/Corticotropin, from the Anterior Pituitary 2. ) Gs signaling pathway

Question 83

Describe Type 3 Hyperlipoproteinemia, i.e. cause(s), clinical presentation, symptoms.

Answer 83

Characterized by ApoE2 apoprotein (ApoE3 is the normal variant), which causes LOW AFFINITY for binding of chylomicron elements --> This causes increased high blood lipid content and HYPERCHOLESTEROLEMIA. -Lipid deposits primarily located in the PALMAR CREASES (unique to Type 3).

Question 84

How do macrophages recognize LDL in the endothelium, i.e. what receptors are utilized? How are they different from liver receptors?

Answer 84

SRA (scavenger receptors): They differ from liver receptors in that SRA have NO REGULATION and will continue to ingest LDL and become completely filled with LDL. They then release growth factors and cytokines, which stimulates migration of smooth muscle cells from the media to the intima, then becoming more foam cells.

Question 85

1. ) What type of nervous system effect is elicited by angiotensin and ADH? 2. ) What blocks the effects of these hormones?

Answer 85

1. ) Sympathetic (dry) 2. ) ACE inhibitors block the formation of Angiotensin II, thereby eliminating all sympathetic response in the renal system.

Question 86

What types of amino acids are alanine, aspartate, glutamic acid?

Answer 86

Glucogenic amino acids

Question 87

What is the ultimate consequence of increasing number of foam cells?

Answer 87

Foam cells form and are engulfed by the collagen layer they produce. This continues to increase and cause CONSTRICTION OF THE VASCULATURE. ***ALSO, collagen can cause clots to form WHEN THE VASCULATURE IS EXPOSED TO COLLAGEN, thereby occluding the vasculature and perhaps BREAKING OFF and causing and EMBOLISM --> if it goes to heart = MI, to brain = STROKE***

Question 88

What is the mechanism of LDL oxidation and plaque formation?

Answer 88

1. ) Damage of endothelium (from environmental factors, smoking, or already oxidized LDL etc.) allow PERMEABILITY TO LIPOPROTEINS AND MIGRATION OF CELLS TO UNDERLYING LAYER. 2. ) Once LDL leaves plasma and enters extracellular space, it becomes VERY SUSCEPTIBLE to OXIDATION OF LIPIDS. Further oxidation of LDL occurs upon arrival in endothelium (intima).

Question 89

What drug treats hyperammonemia by binding Glutamine?

Answer 89

Buphenyl

Question 90

The discoidal, nascent HDL contains a surface ______, which was produced in _______.

Answer 90

Nascent HDL contains a surface ApoA-1, which was produced in the liver.

Question 91

Give the site of synthesis (from outermost to innermost) and examples (n) for the following classes of adrenal hormones: 1. ) Mineralcorticoids (2): 2. ) Glucocorticoids (1): 3. ) Adrenal androgens (3): 4. ) Catecholamines (2):

Answer 91

1. ) Mineralcorticoids (2): Zona glomerulosa, e.g. Aldosterone, deoxycorticosterone. 2. ) Glucocorticoids (1): Zona Fasiculata, e.g. Cortisol, Corticosterone. 3. ) Adrenal androgens (3): Zona Reticularis, e.g. Dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione. 4. ) Catecholamines (2): Medulla, e.g. Epinephrine, norepinephrine.

Question 92

What is the process by which LDL is taken into a cell?

Answer 92

Receptor mediated endocytosis

Question 93

What is the function of lipoprotein lipase (LPL) in general and 1.) in the fed state, and 2.) in a fasting state? 3.) Where is [LPL] highest?

Answer 93

LPL degrades TAG from chylomicrons to be released into tissue for storage or usage. 1. ) In the FED STATE, insulin increases and...LPL is increased in ADIPOSE = storage of TAG in adipose, and decreased LPL in muscle. 2. ) Fasting means DECREASED insulin and...INCREASED LPL in muscle = ENERGY. 3. ) Highest [LPL] in CARDIAC TISSUE...FA = energy for contraction.

Question 94

1. ) What is the fate of cholesterol ester inside HDL2 as it returns to the liver? 2. ) What is the fate of HDL2 after this? 3. ) What is this entire process called?

Answer 94

1. ) Some of CE is transferred to VLDL via CETP, which becomes LDL, and CE is taken up by the liver. 2. ) HDL2 is recognized by SCAVENGER RECEPTOR (SRB-1) on liver ----> Then CE is RELEASED TO LIVER ---> and HDL2 becomes HDL3. 3. ) Reverse cholesterol transport

Question 95

What disease will cause protein to be found in feces? What is compromised in the disease?

Answer 95

Cystic fibrosis: Mucus plugs pancreatic secretion.

Question 96

Mutations in which region of the nuclear receptor can cause oncogenic transformation?

Answer 96

The hormone-binding domain

Question 97

The function of HDL is called _____ ______ _______

Answer 97

Reverse cholesterol transport.

Question 98

Nascent chylomicrons receive _____ and ______ in the plasma from circulating _______. At that point, they are considered _______.

Answer 98

Receive E and C-II in the plasma from circulating HDL. At that point they are considered MATURE.

Question 99

Summarize "reverse transport of HDL (good cholesterol)" in one phrase, then in FIVE STEPS

Answer 99

"Take up cholesterol from non-hepatic (peripheral) tissue, and return it to the liver as cholesterol esters" 1. ) Efflux of cholesterol from peripheral tissues transport proteins pumped to HDL3. 2. ) Esterification of cholesterol by LCAT --> HDL2 3. ) Removal of some CE to VLDL via CETP 4. ) Binding of HDL2 to liver SR-B1 receptors and other stereogenic cells --> Transfer of CE into these cells for BILE ACID or STEROID SYNTHESIS. 5. ) Recycling lipid depleted HDL3 into blood. (1: 04 lecture 32)

Question 100

Presence/expression of specific receptors on target cells can is determined by what two factors?

Answer 100

1. ) Tissue-specific expression | 2. ) Developmentally regulated expression

Question 101

What deficiency do high levels of arginine indicate?

Answer 101

Arginase

Question 102

1. ) What is the recommended level of total blood cholesterol for a healthy person? 2. ) What is the DESIRABLE/IDEAL level? 3. ) What is borderline high, and high?

Answer 102

1. ) < 200 mg/dL 2. ) < 130 mg/dL 3. ) Borderline = 130-159, High = >160 mg/dL

Question 103

What is our main storage source for protein?

Answer 103

No special storage form, except... ---> MUSCLE

Question 104

The liver recognizes ________ for chylomicron remnant re-uptake. What do the remnants contain at this point?

Answer 104

E-3. The remnants are rich in cholesterol ester.

Question 105

What drug is used to treat hyperammonemia by activating CPS 1?

Answer 105

Cabaglu

Question 106

a. ) List the effects glucocorticoids elicit in response to stress (4), and what stimulates their production b. ) What are the TWO main corticosteroids?

Answer 106

a.) *Glucocorticoid production stimulated by ACTH* Responses to stress: 1.) Increased protein catabolism 2.) Increased gluconeogenesis (increased PEPCK) 3.) Increased apoptosis of T cells (= immunosuppression) 4.) Increased Na+ retention (Hypertension) b.) Cortisol, Corticosterone

Question 107

What happens to about 40% of cholesterol in LDL?

Answer 107

40% carried to extrahepatic tissues for lipid synthesis, e.g. adrenocorticoid, gonads. Used for synthesis of steroids, vitamin D, membranes, etc.

Question 108

1. ) Give average HDL levels in men 2. ) Average women 3. ) An HDL of _____ gives some higher protection against heart disease. 4. ) HDL < _____ is higher risk.

Answer 108

1. ) 40-50 mg/dL 2. ) 50-60 mg/dL 3. ) 60 mg/dL 4. ) <50mg/dL for women

Question 109

What is the half-life of proteins influenced by (2)? give examples (two for the first)

Answer 109

1. ) N-terminus: Ser = longer half-life, Asp = shorter half-life 2. ) PEST sequence: Proline (P), Glutamic Acid (E), Serine (S), Threonine (T). *PEST functions as a proteolytic signal to target proteins for degradation...thus, SHORTER HALF-LIVES*

Question 110

1. ) How are AA absorbed into the enterocytes? | 2. ) How are Di- and Tri-peptides absorbed?

Answer 110

1. ) Na+ secondary active transport: AA enters w/ Na+ and via carrier protein. ATPase on portal side pumps K+ in, and Na+ out. 2. ) Absorbed via H+ transport at the small intestine brush border: Na+ in and H+ out creates proton gradient. AA enter with H+ via its created gradient.

Question 111

In a VERY general sense, what occurs under HIGH [cholesterol] conditions (2)?

Answer 111

Under HIGH [cholesterol], there is a DECREASE in HMG CoA reductase and LDL receptors.

Question 112

Which hormones (and their broad category) are made in the following organs: 1. ) Testis (2) 2. ) Ovary (3) 3. ) Placenta (3) 4. ) Peripheral tissue (2)

Answer 112

1. ) Testis (Androgens): Androstenedione (produced in gonads and adrenal glands), Testosterone 2. ) Ovary (Estrogens, androgens): Estradiol (estrogen), androstenedione (androgen), Progesterone. 3. ) Placenta (Estrogens): Estradiol, estriol, progesterone 4. ) Peripheral tissue (estrogens): Estrone, estradiol

Question 113

What are the three main ammonia transports in the body? Where from and to?

Answer 113

Glutamine: NH3 incorporated into urea Alanine: Glucose-Alanine cycle from MUSCLE to LIVER Ammonia: from UREASE (bacteria) --> INTESTINES to LIVER

Question 114

1. ) What gives VLDL (pre-ß), LDL (ß), HDL (alpha), and chylomicrons their density? 2. ) What is the largest and most dense of the above lipoproteins? 3. ) Which is the smallest and most dense?

Answer 114

1. ) Protein, not lipids. 2. ) Chylomicrons 3. ) HDL (small, with lots of APOPROTEIN)

Question 115

Which direction is favored for transamination in the following scenarios: 1. ) After a meal and you are well-fed 2. ) When AA's are needed for growth or protein synthesis 3. ) Fasting

Answer 115

1. ) Amino acids broken down, ammonia --> urea in kidney 2. ) Alpha-amino group added to alpha-ketoglutarate to make glutamic acid (AA) 3. ) Muscle protein broken down, carbon skeleton used to make glucose, kidney used to remove ammonia, liver and kidney remove urea

Question 116

1. ) What happens to the cholesterol released during LDL metabolism? 2. ) What happens to this process when [cholesterol] is high?

Answer 116

1. ) Prior to transport out of the lysosomes, the cholesterol is esterified for storage by Acyl CoA Cholesterol Acyltransferase (ACAT). 2. ) Esterification is INCREASED under high [cholesterol] conditions.

Question 117

List the precursors leading up to LDL

Answer 117

VLDL --> IDL --> LDL

Question 118

What is BUN? What does high BUN indicate?

Answer 118

Blood Urea Nitrogen: Common blood test when looking at renal function. HIGH BUN indicates kidney filtration malfunction.

Question 119

What does Adenosine Deaminase do?

Answer 119

Liberates ammonia from NUCLEIC ACIDS

Question 120

1. ) In the glutamate dehydrogenase reaction, Alpha-KG --> Glu uses _____ and occurs in the ______. 2. ) Glu --> Alpha-KG uses _____ and occurs in the ______.

Answer 120

1. ) Uses NADPH and occurs in the BRAIN (because the rxn needs electrons) 2. ) Uses NAD+ and occurs in the LIVER (because the reaction needs to donate electrons)

Question 121

The DNA binding region actually binds as a _____ using ______.

Answer 121

Binds as a DIMER, using Zn2+ (Zinc) Finger Motifs.

Question 122

What does D-Serine do?

Answer 122

It is a coagonist for endogenous N-methyl D-aspartate receptor (NMDAR), which binds Glu, i.e. D-Serine increases NMDAR affinity for Glu. *THIS CAN LEAD TO INCREASED [Glu] and EXCITOTOXICITY*

Question 123

What are the two primary mechanisms for production and transfer of ammonia?

Answer 123

1. ) Deamination: Removal of amino group and formation of keto acid, e.g. alpha-ketoglutarate...Amino group then removed as NONTOXIC UREA. 2. ) Transamination: Transferring amino group between AA to carbon skeleton of AAs. Glutamate removes ammonia in liver, then released as UREA.

Question 124

1. ) What are the effects of androgens (6)? | 2. ) What are the primary androgens (5)?

Answer 124

1. ) They promote...spermatogenesis, virilization (development of secondary sex characteristics), and bone maturation. They also DECREASE fat deposition, and INCREASE muscle mass. They also control aggression. 2. ) DHEA, DHEA-S, Androstenedione, Testosterone, 5-alpha-Dihydrotestosterone.

Question 125

1. ) What is the main constituent(s) of LDL? What is comparatively low? 2. ) What is the most significant apoprotein on LDL, and what other protein does it shares the same gene with?

Answer 125

1. ) Cholesterol and cholesterol esters. It has low triglycerides. 2. ) ApoB-100. It shares the gene with ApoB-48 (in the intestines), but ApoB-100 is a 100% transcribed version of this gene.

Question 126

1. ) What is the cause of osteoporosis after menopause? | 2. ) What is an effective treatment?

Answer 126

1. ) Menopause causes loss of Estradiol (E2), which inhibits the activation of osteoclasts. Thus, osteoclast activity is increased, causing increased bone resorption. 2. ) Estrogen replacement therapy after menopause. Less risky PRIOR to age 60.

Question 127

List and describe the steps (4) in conversion of cholesterol to pregnenolone *first step of steroid hormone biosynthesis* (i.e. location, enzymes, reactants/product/intermediates, and *regulation*)

Answer 127

Conversion of cholesterol to pregnenolone in mitochondria: a. ) Cholesterol esters broken down in cytosol to cholesterol and FA by...Cholesterol Ester Hydrolase (CEH). b. ) Cholesterol transported to mitochondria by Steroidogenic Acute Regulatory Protein (StAR). c. ) Then, P450scc enzyme cleaves cholesterol side chain to produce...PREGNENOLONE. d. ) Pregnenolone then transported out of mitochondria and into the ER to be converted to steroids. - Regulation: Hormonal control by PITUITARY HORMONES (positive regulation)

Question 128

ApoB gene RNA editing in the intestines occurs ________

Answer 128

Post-translationally (around 34:00 of lecture 32)

Question 129

How are extra degraded protein byproducts used (2)?

Answer 129

1. ) Nitrogen: Removed as urea | 2. ) Carbon: Glucogenic or Ketogenic

Question 130

Describe the regulation processes of cholesterol synthesis in conditions of high cholesterol concentration (2 different methods)

Answer 130

1. ) Transcriptional regulation by [cholesterol] - Under HIGH [cholesterol]: a. ) Decrease in expression of HMG-CoA reductase = DECREASE in DE NOVO (from the beginning) cholesterol synthesis. b. ) Decrease in expression of LDL receptors (down regulation) = Decreased cholesterol uptake and increased LDL cholesterol is plasma. 2. ) Inhibition BY CHOLESTEROL (negative feedback) - Under high [cholesterol]: Inhibition of HMG-CoA reductase = decrease in DE NOVO (from the beginning) cholesterol synthesis.

Question 131

What are symptoms of Addison's disease? Cause?

Answer 131

Bronzing of skin, hypoglycemia, changes in distribution of body hair, weight loss, etc. -It is an autoimmune disorder

Question 132

Concerning TC/HDL ratio, what is: 1. ) The goal ratio 2. ) Optimum ratio 3. ) What does an increased and decreased ratio indicate?

Answer 132

1. ) < 5:1 2. ) 3.5:1 3. ) Increased = higher risk of heart disease, decreased = lower risk

Question 133

How does LDL synthesis regulation work on the nuclear level under LOW [cholesterol] conditions, i.e. --> 1.) What controls the transcription the enzymes needed for synthesis, and 2.) How does it work (3 steps)?

Answer 133

1.) Controlled by Sterol Regulatory Element-Binding Protein (SREBP2): An integral ER membrane-bound TRANSCRIPTION FACTOR (protein). 2. ) Under LOW [CHOLESTEROL]: a. ) SREBP2 is cleaved from ER and brought to Golgi with SREBP cleavage-activating protein (SCAP). b. ) In Golgi, two proteases activate SREBP2, which then moves to the NUCLEUS. c. ) In the nucleus, SREBP2 binds to Sterol Binding Element (SRE) upstream from the target genes and INCREASES EXPRESSION of target genes: HMG-CoA reductase, LDL receptor, HMG-CoA reductase.

Question 134

What amino acid has the highest blood concentration?

Answer 134

Glutamine

Question 135

The Urea Cycle involves _____ high energy bonds

Answer 135

4

Question 136

What induces the urea cycle (2)?

Answer 136

1. ) High protein diet = increased [amino acid] = increased Arg = increase in N-Acetylglutamate = increase in CPS1 = Increase in ORNITHINE in UREA CYCLE and INDUCTION of synthesis of urea enzymes 2. ) Starvation: HIGH GLUCAGON LEVELS. - Breakdown of AA --> glucose (decreases as brain starts to use ketones) - Glucagon increases transport of Ala into liver for gluconeogenesis.

Question 137

Excess fatty acids that are converted to TG in the liver are sent via _____ into the blood.

Answer 137

VLDL

Question 138

All steroid hormones are made from ______

Answer 138

Cholesterol

Question 139

Describe the LDL receptors within the membrane of target tissues (two main things)

Answer 139

1. ) LDL receptors are NEGATIVELY CHARGED GLYCOPROTEINS that are clustered in pits on cell membranes. 2. ) The CYTOSOLIC SIDE of the pit is coated with the protein CLATHRIN, which STABILIZES the pit. p. 426

Question 140

ApoCII and ApoE are donated and received back by _______

Answer 140

HDL

Question 141

LDLs are recognized by _______ receptor on target tissues. What type of protein?

Answer 141

ApoB-100/E, and integral protein in plasma membrane of tissues.

Question 142

1. ) HDL is mainly formed in ________ 2. ) Chylomicrons made in _______ 3. ) VLDL made in ______

Answer 142

1. ) The blood, to a lesser extent in the intestines and liver. 2. ) Intestines 3. ) Liver

Question 143

If urea happens to get into the intestine, how can it become ammonia?

Answer 143

via intestinal bacterial UREASE

Question 144

1. ) How long do steroid hormones generally take to work? | 2. ) How do they affect target tissue?

Answer 144

1. ) Slow – Hours to days. 2. ) They bind to specific receptor proteins in target cells and activate Hormone or Steroid Response Elements (HREs and SREs), which either INCREASE or DECREASE TRANSCRIPTION of specific genes.

Question 145

What is the mechanism for the "morning after pill," i.e. what does it act upon?

Answer 145

Since progesterone is needed for nidation (implantation), the morning after pill is a PROGESTERONE ANTAGONIST that blocks the receptor for progesterone.

Question 146

What purpose can ammonia (NH3) serve in the kidney

Answer 146

Induced under acidosis, it can remove excess acid [H+], i.e. buffer, become AMMONIUM, and be excreted as urine.

Question 147

1.) What is a short half-life (in general). What type of proteins have short half-lives (2)? Which has the shortest?

Answer 147

* Minutes or hours* 1. ) Misfolded proteins 2. ) Some regulatory proteins - Ornithine carboxylase has the shortest (11 minutes)

Question 148

Describe Tangier Disease 1. ) What is it caused by? 2. ) Clinical presentation (7)

Answer 148

1. ) Defective ABCA1 transporters (used to transport cholesterol out of the cells)...thus, CHOLESTEROL ESTERS remain inside of the cells and accumulate. 2. ) Blood hypercholesterolemia, tonsils appear orange-yellow and enlarged, hepatosplenomegaly, MARKEDLY REDUCED HDL levels, neurologic abnormalities (e.g. peripheral neuropathy), clouding of cornea, premature cardiovascular disease.

Question 149

Describe the body's response to endothelial injury caused by oxidized LDL (3 steps)

Answer 149

1. ) Monocytes adhere to endothelial cells, move to the subendothelium (intima), and are transformed into macrophages. 2. ) Macrophages consume excess modified (oxidized) lipoprotein (LDL), becoming FOAM cells. 3. ) Foam cells accumulate, releasing growth factors and cytokines that stimulate the migration of smooth muscle cells from the media to the intima. There, they proliferate, produce collagen, and take up lipid, potentially becoming foam cells.

Question 150

What is the clinical presentation of CYSTINURIA?

Answer 150

Defect in reabsorption of BASIC AAs at PROXIMAL TUBULE – These AA then appear in URINE. *Clinically: High concentration of Cystine in urinary tract = precipitation of cystine = KIDNEY STONES

Question 151

How does a proteasome degrade a protein (4)?

Answer 151

1. ) Proteins tagged with Ub are recognized by the proteasome (a barrel-shaped protein complex) 2. ) The proteasome unfolds the protein, de-ubiquitinates protein, then degrades it into fragments. 3. ) Protein further degraded by cytosolic proteases into AMINO ACIDS 4. ) Ub is recycled

Question 152

Describe Hyperlipidemia Type 5 (four things)

Answer 152

1. ) Combination of hypertriglyceridemia and hyperchylomicronemia. 2. ) Increased VLDL production. 3. ) Decreased LPL production 4. ) Chylomicrons and VLDL are elevated.

Question 153

* **Describe the cleaving specificity for the following proteolytic enzymes and give examples*** 1. ) Trypsin 2. ) Chymotrypsin 3. ) Elastase 4. ) Carboxypeptidase

Answer 153

1. ) Basic AA, e.g. Arg, Lys (KNOW THE BASIC AAs) 2. ) Bulky AA, e.g. Met, Leu, Phe, Tyr, Trp 3. ) Small AA, e.g. Ala, Gly, Ser 4. ) Carboxyl terminus, e.g. Ala, Ile, Leu, Val, or Arg, Lys

Question 154

After a fat-rich meal, the lymph appears ______ due to _______.

Answer 154

Appears MILKY due to CHYLOMICRONS.

Question 155

Oxidative deamination occurs most rapidly with _____ via _______ in the liver and kidney.

Answer 155

With GLUTAMATE via GLUTAMATE DEHYDROGENASE

Question 156

1. ) IDL is converted to LDL via what? How does it accomplish this? 2. ) What receptor is left on the LDL?

Answer 156

1. ) Hepatic triglyceride lipase (HTGL): Removes TG from IDL (which goes on to the liver). Leaving a high concentration of cholesterol (after removing TG) means that there is now LDL. 2. ) Only B-100 remains on LDL.

Question 157

What is the only location where free AA are found?

Answer 157

Portal vein of liver

Question 158

How can neurotransmitters be a source of ammonia?

Answer 158

Through MONOAMINE OXIDASE (MAO): They can convert CATECHOLAMINES, e.g. epinephrine, norepinephrine, L-dopa, to ammonia.

Question 159

Describe Type 1 Hyperlipoproteinemia, i.e. what it is called, what is the physiologic cause, symptoms (4)

Answer 159

AKA – Familial lipoprotein lipase deficiency = The accumulation of chylomicrons in plasma...causes the following --> - Serum appears milky - Hypertriacylglyceroemia - No lipid deposits - Increased risk for acute pancreatitis

Question 160

What is the method extracellular protein degradation?

Answer 160

Lysosomal degradation via acid hydrolases

Question 161

What is the role of Vitamin B6 in transamination?

Answer 161

It is the intermediate carrier of the amino group.

Question 162

1. ) What enzyme is involved in TRANSAMINATION? | 2. ) What enzyme is involved in DEAMINATION?

Answer 162

1. ) Aminotransferase | 2. ) Glutamate Dehydrogenase

Question 163

What is the fate of VLDL after passing through peripheral capillaries (explain as percentages)?

Answer 163

- 50% of VLDL remnant picked up by liver apoE receptor, while some VLDL will become INTERMEDIATE DENSITY LIPOPROTEIN (IDL)...some of which can be endocytosed by liver. - other 50% of remnant VLDL will change density from INTERMEDIATE DENSITY LIPOPROTEIN (IDL) to LDL.

Question 164

When will see ALT and AST in the blood stream? Why?

Answer 164

When there is LIVER DAMAGE. Why? Because the majority of ALT and AST are in LIVER HEPATOCYTES (intracellularly). Therefore, they are released when after liver injury.

Question 165

What mediates TRANSAMINATION in alanine? Cofactor?

Answer 165

``` DEAMINATION OF ALANINE Alanine Transaminase (ALT): Using Vitamin B6 as cofactor. ```

Question 166

What two treatments for hyperammonemia does Ammonul incorporate?

Answer 166

Phenylacetate and Benzoate