Exam3 2015 Flashcards
(154 cards)
1
Q
- ) Where is aldosterone produced?
- ) What hormone induces its production?
- ) What is #2 produced from, and by what?
A
- ) Outer layer (zona glomerulosa) of the adrenal cortex.
- ) Angiotensin II
- ) Angiotensin II is produced from angiotensin I by angiotensin-converting enzyme (ACE) – an enzyme found predominantly in the lungs but also distributed widely in the body.
p. 436
2
Q
What are the effects of Angiotensin II (5)?
A
1.) Increased SNS activity.
2.) Tubular Na+ Cl- reabsorption, and K+ secretion = H2O retention.
3.) Aldosterone secretion (causes more of #2).
4.) Arteriolar vasoconstriction, increased BP (vasopressin).
5.) ADH secretion from the posterior pituitary = H2O absorption from the renal collecting duct.
#15
3
Q
- ) Patients with untreated PKU may show a deficiency of pigmentation, a result of defect in the first step Phe metabolism.
- ) What is this step?
A
- ) deficiency of pigmentation
- ) The hydroxylation of tyrosine by tyrosinase, which is the first step in the formation of the pigment melanin, is inhibited in PKU.
p. 495
4
Q
- ) The rate-limiting step in bile acid synthesis is the introduction of a ______ at ______ of the _______.
- ) Which enzyme catalyzes this rate-limiting step?
A
- ) a hydroxyl group at carbon 7 of the steroid nucleus.
- ) 7-α-hydroxylase
p. 416
5
Q
_________ is the parent compound for all steroid hormones.
A
Pregnenolone.
p.435
6
Q
ACTH is one byproduct of the proteolytic processing of the gene product of the _____________ gene.
A
Proopiomelanocortin (POMC) gene. #12
7
Q
What compounds become depleted in PKU?
A
Lack of Tyr leads to depleted CATECHOLAMINE NTs, while phenylacetate and phenyllactate inhibit ACh synthesis. #9
8
Q
The density of HDL increases with what?
A
Increasing [apoprotein] #5
9
Q
Bile salts increase the ________ available for absorption.
A
[monomeric lipid] #21
10
Q
- ) Nitric oxide (NO) is made from ____ in a two-step reaction involving _______.
- ) What enzyme and cofactor is required?
- ) NO signals via ______ causing ________ and _________.
A
1.) Arg in a two-step reaction involving molecular O2.
2.) Nitric oxide synthase, BH4 cofactor.
3.) NO signals via cGMP causing vasodilation and increased blood flow.
L29, #30
11
Q
Assembly of the apolipoproteins and lipid into chylomicrons requires ___________, which loads _____ with lipid in the _______.
A
- microsomal triglyceride transfer protein (MTP).
- loads apo B-48 with lipid in the SER.
p. 422
12
Q
- ) Give the normal LFT levels/range for AST and ALT
2. ) Which enzyme, AST or ALT is more sensitive and why?
A
1.) AST normal range: 10-34 IU/L
ALT normal range: 8-37 IU/L
2.) AST because it is present in higher amounts.
#44
13
Q
- ) What is the underlying pathology for Cushing’s Syndrome? Give three possible causes (two endogenous, one exogenous).
- ) Give six symptoms (including ones that are exclusive to males or females).
A
1.) Excess cortisol production –END: Pituitary tumor (70%) and Adrenal tumor (15%), EXO: Overuse of steroids (e.g. prednisone).
2.) Moon face, edema, gynecomastia (man boobs), fat deposits and face and back of shoulders, thin skin, amenorrhea (females).
#30
14
Q
The long-chain length fatty acids, having entered the enterocyte, are first converted into their activated form by _____________________.
A
fatty acyl-coenzyme A (CoA) synthetase (thiokinase)
p.332
15
Q
- ) What is the underlying pathology for Addison’s Disease? Give two possible causes.
- ) Give two metabolic consequences.
- ) Give five symptoms.
A
1.) Cortisol and aldosterone deficiency –Commonly autoimmune.
2.) Increased ACTH and MSH (hyperpigmentation), and salt wasting.
3.) Bronze pigmentation, hypoglycemia, postural HYPOtension, ∆ body hair distribution, GI disturbances.
#31
16
Q
List the three steps to sterol-dependent regulation of cholesterol synthesis and the overall conclusion.
A
1.) SREBP2 is cleaved from ER and is brought to Golgi with SCAP*
2.) In Golgi, 2 proteases activate SREBP2→moves to nucleus.
3.) In nucleus, SREBP2 binds to SRE** upstream from the target genes → increases expression of HMG-CoA reductase
Therefore: under low cholesterol→increase in
de novo cholesterol synthesis
#24
17
Q
The enzymes involved in TAG, cholesterol, and phospholipid synthesis are located in the _______ of ________ cells, which is also the location of ______ synthesis.
A
- located in the smooth ER of intestinal mucosa cells.
- Chylomicron synthesis.
p. 422
18
Q
- ) _______ is an inducer of BCKD (branched-chain keto acid DH complex) expression.
- ) Thus, plasma [BCAA] increase in patients with _________, why?
- ) What other disease can result from this, what causes it?
A
1.) Insulin
2.) Type 2 Diabetes, due to insulin resistance.
3.) Maple Syrup Urine disease – deficiency of BCKD = higher [BCAA], makes urine smell like burnt maple syrup.
#21
19
Q
- ) What is the initial and rate-limiting reaction of steroid synthesis?
- ) What catalyzes this step?
A
- ) The initial and rate-limiting reaction converts cholesterol to the 21-carbon pregnenolone.
- ) It is catalyzed by the cholesterol side-chain cleavage enzyme desmolase, a cytochrome P450 (CYP) oxidase of the inner mitochondrial membrane.
p. 435, #7
20
Q
Give the Friedewald formula for LDL estimation
A
LDL = TC –HDL – (TG/5.0mg/dL) #60
21
Q
Phe has a high affinity for _________.
A
AA transporters. #9
22
Q
List the three hormonal regulators of cholesterol synthesis that control gene expression. List their effect as well.
A
Insulin and thyroxine:
Up-regulation of HMG-CoA Reductase expression→ increase in cholesterol synthesis
Glucagon: Down-regulation of HMG-CoA Reductase expression→ decrease in cholesterol synthesis. #25
23
Q
_________, a ________ is given to the mother shortly before delivery to induce surfactant production.
A
Dexamethasone, a glucocorticoid (corticosteroid)
24
Q
What is the first step in de novo FA synthesis?
A
The first step in de novo fatty acid synthesis is the transfer of acetate units from mitochondrial acetyl CoA to the cytosol.
p.345
25
What treatment prevents hepatotoxicity in HT1 and how?
```
Nitisinone prevents the formation of hepatotoxic succinylacetone.
#14
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26
Describe the mechanism of antihistamines
```
Antihistamines bind to histamine H1 receptors and act as inverse agonists (they bind to the same site as histamine but exert the opposite effect, e.g., cetirizine, loratadine).
#29
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27
1. ) What is the major regulatory step of the urea cycle?
2. ) What enzyme?
3. ) What is needed as a positive allosteric activator (and what is it activated by)?
4. ) Where does this reaction take place (organelle and organ)?
1.) Formation of carbamoyl phosphate by...
2.) Carbamoyl phosphate synthetase (CPS I).
3.) N-acetylglutamate – activated by ARGININE.
4.) Mitochondrial matrix of liver (and intestine).
#15, p.464
28
1. ) What is the function of ApoE3?
| 2. ) Presence of _______ is a predisposing genetic risk factor for late-onset Alzheimers.
1.) Needed for recognition by hepatic receptors.
2.) ApoE4 isozyme (p.426).
L25 #10
29
What causes Albinism and how?
```
Tyrosinase deficiency – The pigment, melanin, is made from Tyr by Tyrosinase in melanocytes.
#17
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30
1. ) What is the underlying pathology for Conn's Syndrome? Give three possible causes (two endogenous, one exogenous).
2. ) Give one main symptom and its four metabolic/ionic associations.
3. ) Two treatment options
1.) Overproduction of aldosterone – Benign adenoma of one adrenal, Bilateral nodular hyperplasia (idiopathic, glomerulosa).
```
2.) HYPERVOLEMIA –
↑Blood volume, ↑Na+
↑Blood pressure
↑ Urine K+, H+
-Metabolic alkalosis
```
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3.) Unilateral Adrenalectomy
Spironolactone/Eplerenone (Aldosterone blockers)
#32
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31
What are the symptoms (and their causes) for 21-Hydroxylase deficiency (3)?
1.) Absence of both mineralocorticoids and glucocorticoids = Salt wasting, hypotension.
2.) Hypoglycemia, lethargy, adrenal crisis (inadequate regulation of glucose in first 3-4 weeks of life).
3.) Virilism, female psudohermaphroditism – Ambiguous genitalia.
*Most common cause of CAH*
#39
32
What is BUN and what is its clinical significance?
```
BUN = Blood Urea Nitrogen – A common blood test to evaluate renal function.
*High BUN is an indication of KIDNEY FILTRATION MALFUNCTION*
#23
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33
Elevated plasma homocysteine is a risk factor for ___________.
```
coronary artery disease (atherosclerosis, DVT).
#25
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34
1. ) Give 2 examples of progestins.
2. ) Give the target tissues of progestins (1).
3. ) Give the effects of progestins (2)
1.) Progesterone, 17α-Hydroxy-progesterone.
2.) Uterus
3.) Nidation (implantation), Maintenance of pregnancy.
#16
35
Where do the two nitrogens in urea come from?
One from Glutamate (Glu), and the other from Asparagine (Asp).
L29, #21
36
What effect does FSH have in men and women?
FSH regulates the growth of ovarian follicles and stimulates testicular spermatogenesis.
p.438
37
In response to severe stress (for example, infection), what hormone induces the production and release of ACTH? Where does the hormone in question come from and where does it stimulate the release of ACTH from?
Corticotropin-releasing hormone (CRH), produced by the hypothalamus, travels through capillaries to the anterior lobe of the pituitary, where it induces the production and secretion of adrenocorticotropic hormone (ACTH).
p.436
38
What is the clinical connection exists between serum bilirubin and liver damage? Clinical presentation?
```
Elevated serum bilirubin results from hepatocellular damage that decreases the hepatic conjugation and excretion of bilirubin.
*Elevated serum bilirubin = JAUNDICE (icterus)*
#46
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39
Relative to other dietary lipids, _______ is only poorly absorbed by the enterocytes.
cholesterol
| p.332
40
1. ) Tyrosinemia, Type II (HT2) is caused by a deficiency what?
2. ) What does this condition cause? (2)
1.) tyrosine aminotransferase
2.) Photophobia, Skin lesions on palms and soles.
#15
41
BH4 is an essential cofactor in the _______ of _______ amino acids, ____, ____ and ____ as well as the production of _____ from _____.
-hydroxylations of aromatic amino acids, Phe, Tyr and Trp.
-production of NO from Arg.
#14
42
What does ALT catalyze the transfer of? What are the products?
The enzyme catalyzes the transfer of the amino group of alanine to α-ketoglutarate, resulting in the formation of pyruvate and glutamate.
p.459
43
Methionine catabolism produces ________, a ________ compound.
```
Succinyl-CoA – A glucogenic compound.
#18
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44
Bile salts are absorbed in the via the _________ in the _________, with less than 5% being lost in ________.
- via the ileal bile acid transporter in the terminal ileum
- the feces
p. 333
45
What are the functions of HETEs in general (1)?
```
Chemotactic agents: act on neutrophils and eosinophils.
#6
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46
In which part of the adrenal gland are catecholamines synthesized? Give two examples of catecholamines.
Catecholamines: Medulla
Epinephrine, Norepinephrine
L26 #5
47
What is the treatment for PKU (2)?
```
Treatment includes limiting Phe in diet together with supplementation of Tyr, Trp and branched-chain amino acids (Val, Leu, Ile).
#9
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48
1. ) What enzymes are defective in Type II - MMA and hyperhomocysteinemia? (Two always, and three others possibly).
2. ) What two things accumulate as a result?
1.) -Defective formation of both adenosyl- and methyl-cobalamin (B12).
-Defective cblC, cblD or cblF.
2.) Homocysteine and Methylmalonyl-CoA.
#28
49
Tyrosinase (a ______ containing enzyme) does not require _____.
-a Cu2+ containing enzyme
-does not require BH4
#17
50
1. ) Give 3 examples of estrogens.
2. ) Give the target tissues of estrogens (1).
3. ) Give the effects of estrogens (5)
1.) Estradiol, Estrone, Estriol.
2.) Reproductive organs (primary and secondary).
3.) Feminization, estrus cycle, ↑fat stores, ↑HDL, ↓testosterone production in males.
#16
51
What compound affecting catecholamine metabolism acts as an anti-depressant and how?
MAO inhibitors by prolonging the activation of Nor and serotonin receptors.
L29, #24
52
1. ) What are the reactants, products, and enzyme involved in the pathway where MMA occurs?
2. ) What are symptoms of MMA type 1? (5)
1. ) Methylmalonyl-coenzyme A (CoA) converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.
2. ) Vomiting, lethargy, hypotonia, altered mental status, hepatomegaly (#22).
- WIKI
53
What activates lipoprotein lipase and where?
ApoC-II – in the capillaries of tissue.
| L25 #10
54
What catalyzes the conversion of histidine to histamine? What cofactor is required?
```
Histidine carboxylase – requires PLP (pyridoxal phosphate/B6).
#29 and notes.
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55
Celiac disease (aka ____-_____ ______) is linked to genetically transmitted ____________ (______).
-aka Gluten-sensitive enteropathy (or Celiac sprue)
-Major histocompatibility cell antigens (MHC).
#18
56
1. ) In the absence of 3β-HSD, what types of hormones may still be synthesized? Show why.
2. ) 3β-HSD is not a _______ enzyme
3. ) What reactions does 3β-HSD catalyze (3)?
1.) no synthesis of either corticosteroids or sex steroids (fatal).
2.) cytochrome P450 enzyme
3.) Pregnenolone to Progesterone, 17-alpha HyPreg to 17-alpha HyProg, and DHEA to Androstenedione.
#35
57
What is the rate-limiting step in catecholamine synthesis from Tyr? Enzyme?
```
Tyr to DOPA – Catalyzed by BH4 (tetrahydrobiopterin).
#23
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58
What are the symptoms (and their causes) for 11ß-Hydroxylase deficiency (3)?
1.) No formation of cortisol or aldosterone – CAH due to increased ACTH.
2.) Accumulation of 11-deoxycorticosterone (11-DOC) causes hypertension due to its mineralocorticoid function = ↑Risk of stroke.
3.) Increased androgen formation leads to virilism (female psudohermaphroditism) = Ambiguous genitalia.
#41
59
Describe the two metabolic states that result in urea cycle induction.
1. ) High Protein Diet = Feed-forward regulation.
- Increase in Arg = Increase in N-AcetylGlu → increase in CPS1.
- Increase in ornithine in Urea Cycle.
- Induction of synthesis of Urea Enzymes.
2. ) Starvation: High Glucagon Levels.
- Breakdown of A.A.--> Glucose
- Decreases as brain starts to use ketones.
- Alanine main gluconeogenic amino acid.
- Glucagon increases transport of Ala into liver → Gluconeogenesis.
#28
60
1. ) Angiotensin I is produced in the blood by cleavage of which inactive precursor (secreted from where)?
2. ) Which enzyme facilitates the cleavage (and where does it come from)?
1. ) Angiotensinogen, secreted by the liver.
2. ) Cleavage is accomplished by the enzyme RENIN, made and secreted by the kidney.
p. 436
61
1. ) What is deficient in Alkaptonuria?
| 2. ) Give two clinical manifestations?
1.) Deficiency of homogentisate oxidase
2.) Homogentisic aciduria, darkening of urine exposed to air and light – autooxidation of homogentisate in the urine followed by polymerization leads to a brownish-black pigment.
#16
62
1. ) In Hereditary Tyrosinemia Type I (HT1), ___________ accumulates and converts to _________, which is _________ (dangerous).
2. ) What three dysfunctions result?
1.) fumaryl-acetoacetate accumulates and converts to succinylacetone which is hepatotoxic.
2.) Inhibits TCA cycle, Inhibits heme synthesis, Renal tubule dysfunction.
#14
63
_________ (________) given to patients deficient in BH4.
Sapropterin (synthetic BH4)
| L29, #14
64
1. ) Increased production of ACTH also leads to increased formation of which three gene products?
2. ) What do those three gene products do?
1.) α, β and γ-MSH.
2.) MSH (melanocyte stimulating hormone, aka melanocortin) causes hyperpigmentation.
#12
65
1. ) What three AAs are used in glutathione synthesis?
| 2. ) Glutathione is also important in the synthesis of ___________ (_____, _____, and ______).
1.) Gly, Cys (remember, glutathione contains SULFUR), and Glu.
2.) Cysteinyl leukotrienes (LTC4, LTD4 and LTE4).
#28
66
What are four clinical signs associated with hyperammonemia?
1.) Glutamine always elevated in blood.
2.) Deleterious astrocyte swelling.
3.) Ammonia plasma levels are increased 2-3 fold in patients with mild to moderate cirrhotic *hepatic encephalopathy (HE)* and up to 10 fold in patients with acute liver failure.
4.) Severe encephalopathy (HE) and up to 10 fold in patients with acute liver failure.
#31
67
1. ) Which enzymes are required to make T3 and T4 and from what precursor?
2. ) Which is the activated hormone, which is the prohormone, and which is the inactive?
1.) Monoiodotyrosine (MIT) and Diiodotyrosine (DIT), from Tyrosine.
2.) T3 = active form, T4 = prohormone, Reverse T3 = inactive.
L29, #25
68
What are the essential AAs? Which are strictly ketogenic?
*PVT TIM HALL always ARGues, never TYRes*
| Phe, Val, Trp, Thr, Ile, Met, His, Arg, *Leu, Lys*
69
Where are ALT and AST found?
Both: Intracellularly within hepatocytes.
AST: Skeletal and cardiac muscle (and other organs) in addition to hepatocytes.
#45
70
What three enzymes are required in creatine synthesis and where do each of their reactions occur?
1.) Transguanylase – Kidney
2.) SAM – Liver
3.) Creatine kinase – Muscle
#27
71
Catecholamine (e.g. Epi, Nor) degradation initially takes one of two catabolic routes. What are they and which enzyme catalyzes each?
1. ) Oxidative deamination – monoamine oxidase (MAO).
| 2. ) O-Methylation – catechol-O-methyl-transferase (COMT).
72
Serotonin is made from _______ by the actions of a hydroxylase requiring _____ and 5-HT decarboxylase, which requires _________.
-made from Tryptophan
-BH4
-pyridoxal phosphate/PLP/Vit B6
#26
73
LDL particles contain much less _____ than their VLDL predecessors and have a high concentration of _______ and _________.
- much less TAG
- high concentration of cholesterol and cholesteryl esters.
p. 426
74
1. ) What class of corticosteroid is cortisol?
2. ) Give its target tissues (3) and...
3. ) Effects (5).
1.) Glucocorticoid
2.) Muscle, liver, adipose, etc.
3.) Response to stress –
↑Protein Catabolism
↑Gluconeogenesis (↑PEPCK)
↓Prostaglandins (inflammation)
↑Apoptosis (T cells) (immune suppression)
↑Na+ retention (Hypertension)
(under some conditions)
#14
75
I.) What are the four/five proteolytic pancreatic enzymes and what is the carbonyl AA cleaving specificity for each (also give the AA cleaving in general terms)?
II.) Each of these enzymes has an active _____ residue which is used during proteolysis; thus, they are called _______.
I.)
1.) Trypsin – Arg, Lys (Basic AAs).
2.) Chymotrypsin – Trp, Tyr, Phe, Met, Leu (Bulky AAs).
3.) Elastase – Ala, Gly, Ser (Small AAs).
4.) Carboxypeptidase A – Ala, Ile, Leu, Val.
Carboxypeptidase B – Arg, Lys.
(C-terminus).
II.) active SERINE (Ser) residue – Serine Proteases.
L27 #14
76
1. ) What are the end products of catecholamine degradation and how are they removed from the body?
2. ) What is pheochromocytoma and what does it cause?
1.) VMA and Homovanillic acid – excreted in urine.
2.) A tumor of the adrenal medulla; causes excessive excretion of VMA.
L29, #24
77
List the four types of lipoproteins in order of decreasing size and give their functions. What increases as they decrease in size?
1. ) Chylomicron deliver dietary TAG from intestines→ peripheral tissues → remnants → liver
2. ) VLDL deliver hepatic TAG → peripheral tissues
3. ) LDL deliver cholesterol to tissues
4. ) HDL deliver removes cholesterol from peripheral tissues → liver (reverse transport); reservoir for some apoproteins
*DENSITY INCREASES AS SIZE DECREASES*
L25 #5
78
Phosphatidic Acid (PA) plays a role in _______ formation and in _______.
ß-amyloid formation and in thrombosis.
| L22, #15
79
The first step in de novo fatty acid synthesis is the transfer of _______ from __________ to the ______.
- transfer of acetate units (via citrate) from mitochondrial acetyl CoA to the cytosol.
p. 345
80
VLDL remnants contain more ______ and less ______ than VLDLs.
```
More cholesterol and less TG.
#16
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81
1. ) What causes defective metabolism of homocytsteine? (Deficiencies of 3 things, or defective ______).
2. ) Risk factors for what five things are increased with elevated plasma homocysteine?
3. ) What are all of the risks in #2 linked to and why?
1.) Deficiency of B6, B12 or folate
Defective cystathionine-β-synthase.
2.) Atherosclerotic heart disease, Stroke, Osteoporosis, Eye lens dislocation, Mental retardation.
3.) Interferes with collagen crosslinking – Inhibits lysyl oxidase.
#27
82
Describe the composition of lipoproteins, i.e. their core and outer surface.
Lipoproteins are composed of a neutral lipid core containing triacylglycerol (TAG) and cholesteryl esters, surrounded by a shell of amphipathic apolipoproteins, phospholipid, and unesterified (free) cholesterol (with -OH facing outwards).
p.420, L25 #4
83
Where is urea synthesized and secreted from?
```
Synthesized in the LIVER, excreted by the KIDNEYS.
#11
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84
1. ) What is the result of Histamine binding to H1 receptors (5)?
2. ) H2 receptors?
3. ) What is the signalling mechanism of H1 and H2?
1.) Binds to H1 receptors → vasodilation and hypotension; bronchoconstriction; & separation of endothelial cells and edema, i.e. responsible for allergic reactions.
2.) Binds to H2 receptors → gastric acid secretion (blocked by H2 antagonists, e.g., cimetidine, ranitidine).
3.) GCPR.
#29
85
1. ) _______ is the rate-limiting step of the Phe metabolic pathway. What cofactor is required?
2. ) Defects in synthesis in each/either of the above compounds leads to what (2)?
1.) PAH activity – Requires BH4.
2.) leads to phenylketonuria (PKU).
a.) PAH deficiency = Classical PKU
b.) Defective BH4 production = 2˚/non-classical PKU.
L30 #5
86
What enzyme converts the pancreatic zymogen trypsinogen to its active form, trypsin? Where is it located?
Enteropeptidase, an enzyme synthesized by and present on the luminal surface of intestinal mucosal cells of the brush border membrane, converts the pancreatic zymogen trypsinogen to trypsin.
p.455
87
Cytosolic citrate may be viewed as a __________.
high-energy signal
| p.345
88
1. ) What is the major methyl-group donor in one-carbon metabolism?
2. ) How is it formed?
1. ) S-adenosylmethionine (SAM).
2. ) Methionine condenses with adenosine triphosphate (ATP), forming SAM, a high-energy compound that is unusual in that it contains no phosphate. The formation of SAM is driven, in effect, by hydrolysis of all three phosphate bonds in ATP.
p. 483, #18
89
1. ) Bile salts are what type of molecules?
2. ) They are conjugated to which amino acids (and what type of amino acid) and what are the names of the structures they form?
1.) Amphipathic molecules (both polar and non-polar).
2.) Glycine or taurine – a sulfated, non-proteogenic amino acid – Glycocholic acid and taurocholic acid.
#15
90
What does picotamide do?
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Picotamide is an inhibitor of thromboxane synthase as well as thromboxane receptor activity.
#18
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91
1. ) What three AAs are necessary in the synthesis of creatine?
2. ) Where does this occur?
3. ) What is the committed step enzyme?
1.) Three AAs necessary – Arg, Met, and Gly.
2.) Occurs in the liver and kidney.
3.) Transguanylase.
#27
92
What are the four uses of pyridoxal phosphate (vitamin B6) in metabolism?
1.) Transamination reactions
2.) DOPA decarboxylase
3.) Cystathionine synthase, Cystathionase
Metabolism of Met→ Cys
4.) Glycogen Phosphorylase – Breakdown of Glycogen
#43
93
1. ) List the AAs that are BOTH gluconeogenic AND ketogenic (5).
2. ) List the purely ketogenic AAs (2).
1.) Both glucogenic and ketogenic amino acids:
Phe, Tyr, Trp, Ile, Thr
2.) Purely ketogenic amino acids:
Leu, Lys
#5
94
1. ) Cystinuria is a defect in the absorption of which AAs (5) and where?
2. ) Where do the AAs appear as a result?
3. ) What is the clinical presentation?
1.) Genetic defect in the reabsorption of Cys,His, Orn, Arg and Lys in proximal tubule in kidney.
2.) These a.a. appear in urine.
3.) Clinically: High concentration of Cystine in urinary tract→ precipitation of Cystine→ kidney stones.
#16
95
1. ) What is the goal cholesterol/HDL ratio?
2. ) Optimum?
3. ) What do higher and lower ratios indicate?
1. ) Goal 5:1
| 3. 5:1
96
What are the two uses of transamination implied by the fact that it is a freely reversible reaction?
1.) After protein rich meal: removes α-NH2 group → urea cycle→ Ammonia removed from the body.
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2.) When a.a. are needed: α-NH2 group is added to α-Ketoglutarate → Glutamate→ Metabolism.
#40
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97
COX-2 induction can be suppressed by ________.
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Steroids
#13
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98
What is hepatic steatosis (aka _______), and when is it seen?
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Hepatic Steatosis (fatty liver): An imbalance between TG synthesis and VLDL secretion.
-Seen in Obesity, IDDM, alcoholics
#21
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99
How does methylmalonic acidemia (MMA) type 1 cause hyperammonemia?
```
due to inhibition of N-acetylglutamate synthetase and CPS-I.
#22
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100
1. ) What class of corticosteroid is aldosterone?
2. ) Give its target tissues (3) and...
3. ) Effects (3).
1.) Mineralocorticoid
2.) Kidney tubules, colon, and parotid gland.
3.) ↑Na+ retention (Hypertension)
↑Water retention
↑Na+ absorption (low salt fluid)
#14
101
1. ) Deficiency of BH4 inhibits the synthesis of _______.
| 2. ) It also inhibits ______ synthesis by ________, leading to ________.
1.) serotonin.
2.) dopa synthesis by tyrosine hydroxylase, leading to secondary PKU.
#26
102
What stimulates the synthesis and secretion of all adrenal steroid hormones and from where?
```
Adrenocorticotropic Hormone (ACTH, Corticotropin) stimulates the production of corticosteroids in the adrenal cortex.
#10
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103
All AAs except _____ and _____ can be synthesized from common intermediates of metabolism; which four common intermediates?
-Tyr and Cys
1.) Pyruvate
2.) Oxaloacetate
3.) α-Ketoglutarate
4.) 3-Phosphoglycerate
#11
104
What are two sources of endocytosed cholesterol?
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Chylomicron remnants, IDL (VLDL remnants).
#60
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105
1. ) ___________ provides the second nitrogen that is ultimately incorporated into urea.
2. ) Where does this occur?
1. ) The α-amino group of aspartate
2. ) Cytosol
p. 465
106
In which part of the adrenal gland are mineralocorticoids synthesized? Give an example of two mineralocorticoids.
Mineralocorticoids: Zona Glomerulosa
Aldosterone, Deoxycorticosterone
L26 #5
107
_______ account for close to 90% of the lipids in a chylomicron.
TAGs
| p.422
108
_____ and _____ are the most abundant phospholipids in most eukaryotic cells. The primary route of their synthesis uses ______ and ______ obtained either from the _______ or from the __________
- PC and PE
- choline and ethanolamine
- either from diet or from the turnover of the body’s phospholipids.
p. 379
109
Give the typical structures of the FA chains (3) on a TAG.
The fatty acid on carbon 1 is typically saturated, that on carbon 2 is typically unsaturated, and that on carbon 3 can be either.
p.352
110
PLs are mainly digested by what? Describe it, its mechanism of digestion, its product(s) and where they are absorbed.
Phospholipase A2: A proenzyme activated by trypsin that requires bile salts for optimum activity.
• Phospholipase A2 removes one fatty acid from carbon 2 of a phospholipid, leaving a lysophospholipid.
• FA and lysophospholipid are absorbed in the ileum from mixed micelles.
#8, p.331
111
What does AST catalyze the transfer of? What are the products?
AST transfers amino groups from glutamate to oxaloacetate, forming aspartate, which is used as a source of nitrogen in the urea cycle.
p.459
112
1. ) Where and why is CCK produced?
| 2. ) What does it act on and what is the result (2)?
1.) Produced by I-cells in the duodenum and jejunum in response to lipids and partially digested proteins.
2.) CCK acts on the gallbladder (causing it to contract and release bile, a mixture of bile salts, phospholipids, and free cholesterol) and on the exocrine cells of the pancreas (causing them to release digestive enzymes).
• It also decreases gastric motility, resulting in a slower release of gastric contents into the small intestine.
p.331
113
1. ) Explain the metabolism of Phe in PKU.
| 2. ) Why is this pathological?
1.) Phe forms phenylpyruvate via PLP (pyruvate to alanin) – which then forms phenylacetate and phenyllactate.
2.) Phenylacetate and phenyllactate are neurotoxic metabolites and accumulate in the brain. They INHIBIT ACh SYNTHESIS!.
#8
114
Give five general biological functions of SAM.
1.) Hormone and NT synthesis (e.g. NE to Epi).
2.) DNA methylation
3.) FA oxidation
4.) Cell proliferation
5.) Energy storage (arginine to creatine)
#19
115
1. ) What is the pathological nature of Hartnup Disorder?
2. ) What compounds are there deficiencies of as a result?
3. ) What two other disorders generate similar symptoms?
1.) Cannot absorb nonpolar amino acids, e.g.Trp properly from the intestine and cannot reabsorb them properly from tubules in the kidneys.
2.) Tryptophan deficient = serotonin, melatonin and niacin deficient.
3.) Tryptophan and niacin deficiencies (“pellagra”)generate similar symptoms.
#19
116
With the exception of ________, prostaglandins are produced and released by nearly all mammalian cells and tissues.
```
RBCs.
#16
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117
In which part of the adrenal gland are glucocorticoids synthesized? Give an example of a glucocorticoids.
Glucocorticoids: Zona Fasiculata
Cortisol
L26 #5
118
1. ) What cofactor is necessary to from Dopamine?
2. ) In what synthetic pathway does this occur?
3. ) What is caused by a loss of dopamine-producing cells? Treatment?
1.) Vitamin B6 (pyridoxal phosphate).
2.) Catecholamine synthesis from Tyr.
3.) Parkinsons Disease – Since dopamine cannot cross the blood-brain barrier, patients are given levodopa (L-dopa) plus carbidopa which inhibits peripheral dopa decarboxylase.
#23
119
1. ) Give 5 examples of androgens.
2. ) Give the target tissues of androgens (2).
3. ) Give the effects of androgens (6)
1.) DHEA, DHEA-S, Androstenedione, Testosterone, 5α-Dihydro-testosterone.
2.) Reproductive organs (primary and secondary),
Muscle.
3.) Spermatogenesis, virilization, bone maturation, ↓fat deposition, ↑muscle mass, aggression.
#16
120
What is the mechanism of statin drugs?
```
Competitive inhibitors of HMG-CoA reductase (structural analogues of HMG-CoA).
#26
```
121
1. ) Absence of which enzyme leads to nonketotic hyperglycemia (aka ______)? What reaction does it catalyze?
2. ) What cofactor is required?
1.) aka Glycine encephalopathy
Glycine Cleavage Complex (GCC): It catalyzes the synthesis of Tetrahydrofolate (THF) from Glycine.
2.) Vitamin B6 (pyridoxal phosphate).
#22
122
What three supplementations can decrease plasma homocysteine levels?
```
Supplementation with B6, B12 and folate decrease plasma homocysteine levels.
#27
```
123
1. ) FA oxidation occurs in the __________.
2. ) Complete oxidation of one molecule of palmitic acid yields ≈ how many ATP?
3. ) Where does FA oxidation NOT occur?
1.) Matrix of the mitochondria.
2.) 129 ATP
3.) FA oxidation does not occur in the BRAIN or in cells that LACK MITOCHONDRIA.
L21, #4
124
What effect does LH have on the male and female gonads?
LH stimulates the testes to produce testosterone, and the ovaries to produce estrogens and progesterone.
p.438
125
Cholesteryl esters are hydrolyzed by _____________ (_________), which produces ______ plus ________.
-pancreatic cholesteryl ester hydrolase (cholesterol esterase).
-cholesterol plus free fatty acids.
#9, p.330
126
Describe the urea cycle genetic deficiency, i.e. pathology, clinical presentation, deficient enzyme, etc.
-Ornithine transcarbamoylase deficiency.
-Leads to hyperammonemia, neurologic sequelae (a condition that is the consequence of a previous disease or injury) = Brain damage, coma, DEATH.
-Death due to high [NH3].
#19
127
Various forms of THF play a vital role in the synthesis what five compounds? (3 AAs, and two other general types of compounds.)
```
Gly, Ser, Met, purines and deoxythymidine mono-phosphate (dTMP).
#17
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128
The effects of PGs vary from one target cell population to another due to ______________.
```
multiple GPCRs and effector enzymes.
#16
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129
What are the functions of prostaglandins in general (2)?
1.) promote inflammatory responses.
2.) Individual PGs may promote (e.g., PGE2) or inhibit (e.g., PGI2) contraction of certain smooth muscles by interacting with different receptors.
#6
130
1. ) What are the three dietary sources of human FAs?
| 2. ) What are the three de novo synthesis precursors?
```
1.) • Triacylglycerols
• Phospholipids
• Essential FA
2.) Acetyl CoA, NADPH, ATP
#4
```
131
Nascent chylomicrons released into plasma circulation receive which two apoproteins at this time and by what?
```
Receive ApoE3 and ApoC-II from CIRCULATING HDL.
#11, p.422
```
132
In which part of the adrenal gland are adrenal androgens synthesized? Give two examples of adrenal androgens.
Adrenal androgens: Zona Reticularis
Dehydroepiandrosterone (DHEA)
Androstenedione
L26 #5
133
1. ) What three enzymes are required for catecholamine synthesis from Tyr and what are their products?
2. ) Where does this pathway occur?
1. ) BH4 – dopa, Vit B6 – Dopamine, Ascorbate (Vit C) – NorEpi.
2. ) Occurs in the adrenal medulla and neurons.
134
What are the two mechanisms by which hyperammonemia is pathological?
1.) Increase in ammonia →depleting the TCA for the brain
2.) Ammonia short-circuits the transport of potassium into the brain’s glial cells→seizures and coma
#34
135
As cortisol levels rise, the release of _____ and ______ is inhibited.
CRH and ACTH is inhibited.
| p.436
136
In circulation, TAGs are removed from chylomicrons by the action of _______ in _______ of what two places?
```
-by the action of LIPOPROTEIN LIPASE in capillaries of SKELETAL MUSCLE and ADIPOSE.
#8
```
137
What are two defects that cause of methylmalonic acidemia (MMA) type 1? aka ______.
```
MMA type 1, aka Isolated MMA:
1.) Defective methylmalonyl CoA mutase (mut 0 or mut -).
2.) Defective formation of adenosyl-cobalamin (B12) (cblA or cblB defect).
#22
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138
1. ) Free cholesterol is absorbed in the _______ and _______ with the aid of ____________.
2. ) _________ inhibits absorption of cholesterol by interfering with _________.
1.) duodenum and jejunum, NPC1-L1 transporter protein
2.) Ezetimibe (Zetia®), interfering with NPC1-L1.
#9
139
_________ suppress production of ALL eicosanoids.
Steroid hormones
140
Where is serotonin found (2) and what does it regulate (6)?
-Serotonin is a monoamine neurotransmitter found predominantly in the gut, but also some in the central nervous system (CNS).
-Regulates mood, appetite, sleep, muscle contraction, and some cognitive functions including memory and learning.
#26
141
1. ) Tyrosinemia, Type III (HT3) is caused by a defect what?
2. ) What does it cause? (1)
1.) p-hydroxyphenylpyruvate oxidase
2.) Intermittent ataxia (loss of muscle coordination)
#15
142
What are the two main functions of creatine?
1.) Energy store in muscle
2.) Rapid conversion of ADP to ATP.
#27
143
________, _________, and __________ are the primary products of lipid digestion in the jejunum.
Free fatty acids, free cholesterol, and 2-monoacylglycerol
| p.331
144
Pepsin is an acid-stable _________ secreted by the chief cells of the stomach as an _________ (or _________), called ________.
- an acid-stable *endopeptidase*
- inactive zymogen, (or proenzyme).
- called pepsinogen
p. 454
145
What are the components of mixed micelles (3)?
Formed by the primary products of lipid digestion in the jejunum (free fatty acids, free cholesterol, and 2-monoacylglycerol), along with bile salts and fat-soluble vitamins (A, D, E, and K).
p.331
146
Folate deficiency causes _________ defects (e.g. ________).
```
neural tube defects (e.g., spina bifida)
#17
```
147
VLDLs transport ________ to _________.
```
HEPATIC TG to peripheral tissues.
#18
```
148
List the five sources of ammonia used in the urea cycle
1.) Transamination to Glu and Deamination → NH3 release.
2.) Glutamine (via glutamine synthase and glutaminase): Non-toxic transport form of NH3.
3.) Urea: Intestinal and gastric bacterial Urease.
Bacteria in lumen of intestine and in stomach (H. pylori) →NH3→ portal system→liver→urea.
4.) Amines: e.g.catecholamines: Monoamine Oxidase (MAO).
-Epinephrine, norepinephrine, L-dopa.
5.) Nucleic acids: release of NH4+ during catabolism.
Example: Adenosine deaminase.
#4-8
149
1. ) Deficiency of which enzyme affects the metabolism of Phe, Tyr and Trp?
2. ) What does this deficiency cause (symptoms)?
1.) BH2 reductase.
2.) It causes causes neurologic dysfunction.
L29, #15
150
Free cholesterol is absorbed via ________ protein in _______ and _______.
-NPC1-L1 protein
-duodenum and jejunum
#21
151
1. ) What enzymes catalyze the conversion of Arachidonic acid to PGH2 (2)?
2. ) Describe where the two forms of the first enzyme are found and what each are used for.
1.) Prostaglandin Synthase – Cyclooxygenase (COX-1 and COX-2) + Peroxidase (PGG2 to PGH2).
2. ) i.) COX-1 is made constitutively in most tissues (bound to SER), i.e. constitutive, and is required for maintenance of healthy gastric tissue, renal homeostasis, and platelet aggregation.
ii. ) COX-2 is inducible in a limited number of tissues (bound to the nuclear envelope) in response to products of activated immune and inflammatory cells.
p. 397
152
Trace the path of urea from its organ of synthesis to its organ of excretion.
```
Urea→hepatic vein→inferior vena cava→ Blood circulation→ descending aorta→ renal aorta→ kidney.
#22
```
153
What are the symptoms (and their causes) for 17alpha-Hydroxylase deficiency (4)?
1.) Blocks production of sex hormones – hypogonadism, ambiguous genitalia (males)
2.) Blocks cortisol but with minimal problem due to increased corticosterone (usually a minor GC in glomerulosa).
2.) Seemingly paradoxically, Na+/fluid retention, and hypertension occur but aldosterone levels are reduced.
3.) Greatly increased 11-DOC* (MC in glomerulosa) causes increased Na+/fluid retention and hypertension → ↓renin → ↓angiotensin II → ↓aldosterone.
4.) CAH due to the absence of cortisol feedback.
#37
154
In 17α-hydroxylase deficiency, no _______ or _______ are produced. What are the resulting changes in hormone levels? (3)
```
-no cortisol or sex steroids are produced.
↑11-DOC, ↑Corticosterone, ↓Aldosterone
#36
```
