Endo/Repro - Biochemistry - Cholesterol & Steroid Hormone Synthesis; Vitamins Flashcards
1
Q
Which organ is the main regulator of body cholesterol?
A
The liver
2
Q
What structure helps transport cholesterol to the liver from the gut?
What protein helps transport cholesterol from the liver to the extrahepatic tissues?
What protein helps transport cholesterol to the liver from the extrahepatic tissues?
A
Chylomicrons
VLDL
HDL
3
Q
Which is the hydrophilic portion of a cholesterol molecule?
Which is the hydrophobic portion of a cholesterol molecule?
A
The 3’-OH
the rest of the molecule
4
Q
True/False.
Cholesterol is a polar molecule made of 4 rings + a 7 carbon tail attached to the 18’-carbon.
A
False.
Cholesterol is a polar molecule made of 4 rings + an 8 carbon tail attached to the 17‘-carbon.
5
Q
What is the initial precursor used to synthesize cholesterol?
A
Acetyl-CoA
6
Q
Describe the basic steps (in simplified form) of cholesterol synthesis.
A
Acetyl-CoA + 3-carbon molecule –> 5-carbon isoprene
5 isoprenes –> 30-carbon squalene
Cyclization –> 27-carbon, 4-ring cholesterol
7
Q
What are the major intermediates of cholesterol synthesis?
A
(18) Acetyl-CoA –>
(6) HMG-CoA –>
(6) mevalonate –>
(6) activated isoprene –>
(1) squalene –>
(1) cholesterol
8
Q
Besides cholesterol, what other metabolites is activated isoprene (pentenyl pyrophosphate) potentially used to synthesize?
A
Vitamins ADEK,
dolichol (used in N-linked glycosylation),
quinone electron carriers
9
Q
What is the substrate and product of the reaction mediated by HMG-CoA reductase?
A
HMG –> Mevalonate
10
Q
How do statins inhibit HMG-CoA reductase?
Via what type of inhibition?
A
They are structural analogs;
competitive inhibition
11
Q
The complex process of squalene cyclizing and hydroxyl groups being added to the subsequent cholesterol molecule is completed by enzymes known as _____________.
A
Monooxygenases
12
Q
Describe the allosteric regulation of HMG-CoA reductase.
A
High ATP –> increased protein phosphatase activity –>
increased HMG-CoA reductase activity
Low ATP –> increased AMP-activated protein kinase (AMPK) activity –>
decreased HMG-CoA activity
13
Q
For what purpose does high ATP levels stimulate HMG-CoA reductase activity?
A
A period of high ATP levels (e.g. the non-fasting state) is the time for membrane repair and compound synthesis
14
Q
What effect does insulin have on HMG-CoA reductase?
What effect do glucagon/epinephrine have on HMG-CoA reductase?
A
Increased activity;
decreased activity
15
Q
What effect does dephosphorylation have on HMG-CoA reductase?
What effect do phosphorylation have on HMG-CoA reductase?
A
Increased activity;
decreased activity
16
Q
Describe the upregulation of HMG-CoA expression.
A
Low [cholesterol]:
SREBP-SCAP moves from the ER to the Golgi –>
SREBP moves to the nucleus and binds SRE –>
Transcription increases
17
Q
What part of the upregulation of HMG-CoA reductase (shown below) is inhibited by high [cholesterol/sterol]? How?
SREBP-SCAP moves from the ER to the Golgi –>
SREBP moves to the nucleus and binds SRE –>
Transcription increases
A
Increased [cholesterol] (or [sterol] in general) causes increased binding of the SREBP-SCAP complex to the protein insig in the ER, preventing movement to the Golgi
18
Q
Describe what happens after a chylomicron is formed in the enterocytes.
A
It moves into a lacteal/the lymphatic system and to the bloodstream;
peripheral tissue liproprotein lipase cleaves the TGs into free fatty acids for uptake;
the remaining chylomicron remnant travels to the liver to deliver its cholesterol
19
Q
Describe the frunctions/relationship between VLDL and LDL.
A
VLDLs: leave liver to drop off TGs/FAs to periphery
VLDLs: become LDLs once they are depleted in TGs/FAs (cholesterol:TG ratio increases)
LDLs deliver cholesterol to periphery
20
Q
What are the four main lipoprotein complexes?
A
Chylomicrons
VLDL
LDL
HDL
21
Q
Name the basic function of each of the following lipoprotein complexes:
Chylomicron
Chylomicron remnant
VLDL
LDL
HDL
A
Chylomicron - deliver fatty acids to the periphery
Chylomicron remnant - deliver remaining cholesterol to the liver
VLDL - deliver fatty acids to the periphery
LDL - deliver cholesterol to the periphery
HDL - return cholesterol to the liver
22
Q
Describe the various relationships between the various lipoprotein complexes (chylomicrons, chylomicron remnants, VLDLs, LDLs, HDLs)
A
23
Q
What is indicated by high LDL levels?
What is indicated by high HDL levels?
A
High cholesterol;
cholesterol being cleared from the periphery
24
Q
List the four main lipoprotein complexes in order of increasing density.
A
Chylomicrons >
VLDLs >
LDLs >
HDLs
25
How is cholesterol moved into the interior regions of a chylomicron or other lipoprotein complex if it is a polar molecule?
How does this happen?
It first must be esterified to a fatty acid (at the cholesterol's 3'-carbon);
via phosphatidylcholine(lecithin):cholesterol acetyltransferase (LCAT or PCAT)
26
How does the enzyme LCAT (PCAT) aid in cholesterol transport?
It esterifies cholesterol so it is more hydrophobic
(and better able to diffuse into the lipoprotein complex interiors)
27
What type of protein is on the outside of lipoprotein complexes, communicating with the external environment and changing the way the complex interacts with tissues?
Apolipoproteins
28
Where will an unesterified cholesterol molecule be found in a chylomicron?
Where will an esterified cholesterol molecule be found in a chylomicron?
The periphery (polar head facing outside);
the interior (hydrophobic molecule)
29
What percentage of each of the following lipoprotein complexes is made up of triglycerides?
Chylomicrons
VLDLs
HDLs
85%
50%
4%
30
Name any intermediates in the synthesis of progesterone from cholesterol.
Cholesterol --\> **pregnenolone** --\> progesterone
31
After cholesterol is converted to pregnonelone and then progesterone, what three major pathways can it then follow?
Conversion to either:
glucocorticoids, mineralocorticoids, or testosterone
32
The corpus luteum is responsible for the synthesis of what major hormone(s)?
Progesterone,
estradiol
33
What effect do mineralocorticoids have on the kidneys?
Increased Na+ reabsorption;
increased K+/H+ excretion
34
What effect can anabolic steroids have on an individual's lipid profile?
What class has the opposite effect?
Increased LDL, decreased HDL;
estrogens
35
Describe some of the generic side effects of improper anabolic steroid use.
Cancer (liver, kidney), jaundice, fluid retention, high blood pressure, an increase in LDL and decreases in HDL, aggression, depression, acne, trembling
36
Describe the gender-specific effects of improper anabolic steroid use.
**Males**: premature baldness, gynecomastia, testicular atrophy, and infertility
**Females**: premature baldness, a deeper voice, hirsutism, clitoromegaly, and oligomenorrhea
37
What effect can anabolic steroid use during pregnancy have on a male fetus?
And a female fetus?
Female features;
male features
38
**True/False**.
Mineralocorticoids aid in the metabolism of carbohydrates, proteins, and lipids.
**False**.
_Glucocorticoids_ aid in the metabolism of carbohydrates, proteins, and lipids.
39
**True/False**.
Glucocorticoids have opposing effects in the liver and in adipose tissue.
True.
40
The opposing effects of glucocorticoids on the liver and adipose tissue centers around what enzyme?
Phosphoenolpyruvate carboxykinase
(increased activity in the liver; decreased activity in adipose)
41
What are the effects of glucocorticoids increasing phosphoenolpyruvate carboxykinase activity in the liver and decreasing it in the adipose?
**Liver**: Increased gluconeogenesis and glyceroneogenesis
**Adipose**: Decreased glycerol 3-phosphate synthesis and subsequent decreased fatty acid uptake
(triglyceride synthesis inhibited)
42
How do increased glucocorticoids levels contribute to insulin resistance?
Increased liver PEPCK activity and decreased adipose PEPCK activity --\>
increased serum free fatty acids --\>
dampened carbohydrate metabolism
43
**True/False**.
The insulin resistance in T2DM is at least partially due to elevated serum fatty acids inibiting proper glucose metabolism.
True.
44
What does the peroxisome proliferator-activated receptor γ do?
What class of medication activates this receptor?
Increases adipose phosphoenolpyruvate carboxykinase activity;
thiazolidinediones (glitazones)
45
What effect do thiazolidinediones (glitazones) exert on individuals with T2DM?
Via what mechanism?
Increased insulin sensitivity;
**PPAR-γ receptor** --\> increased adipose PEPCK activity --\> **increased TG synthesis** --\> improvement of the **lipid profile**
46
**True/False**.
Thiazolidinediones (glitazones) and glucocorticoids have basically the same effect on the body.
**False**.
_Thiazolidinediones (glitazones)_ decrease serum free fatty acids and increase insulin sensitivity.
_Glucocorticoids_ increase serum free fatty acids and decrease insulin sensitivity.
47
What particular effects may present in a newborn if cholesterol biosynthesis is disrupted during embryonic development?
Holoprosencephaly;
genitourinary abnormalities
48
What axis of the neural tube is abnormal in cases of holoprosencephaly?
Ventral-dorsal
49
**True/False**.
Holoprosencephaly may display a wide range of variability.
**True**
(anything from lethality to a single central incisor)
50
What genetic defect is often indicated in holoprosencephaly?
What is its inheritability?
*SHH*;
autosomal dominant
51
What neural effect will result if the *SHH* gene is disrupted during development?
Holoprosencephaly
52
What role does the *SHH* gene play in neural tube development?
Regulation of the ventral-dorsal axis
53
What lipid is necessary for proper functioning of the *SHH* gene?
What may result if this lipid is absent during development?
Cholesterol;
holoprosencephaly
54
What is the basic etiology of Smith-Lemli-Opitz syndrome?
What is its inheritance pattern?
Bile acid / cholesterol deficiency
(huge increase in 7-dehydrocholesterol);
autosomal recessive
55
Describe the clinical presentation of a newborn with Smith-Lemli-Opitz syndrome.
CNS malformations (e.g. microcephaly), severe mental retardation;
cleft palate, anteverted nares, micrognathia;
polydactyly;
genital and cardiac abnormalities
56
What enzyme of cholesterol metabolism is deficient in Smith-Lemli-Opitz syndrome?
What metabolite builds up?
Which are deficient?
7-dehydrocholesterol reductase;
7-dehydrocholesterol;
bile acids, cholesterol
57
What gene is likely affected by the cholesterol deficiency seen in Smith-Lemli-Opitz syndrome?
*SHH*
58
**True/False**.
Many disorders of cholesterol synthesis have accompanying adrenal and gonadal insufficiencies.
True.
59
What is desmosterolosis?
What is deficient?
What is the buildup product?
A disorder of cholesterol synthesis;
lack of cholesterol --\> disrupted *SHH* action;
desmosterol
60
**True/False**.
Phospholipids are essential to normal *SHH* (Sonic the Hedgehog gene) function.
**False**.
_Cholesterol_ is essential to normal *SHH* function.
61
Where are steroid hormone receptors located?
Intracellularly
(in the nucleoplasm, nuclear membrane, or cytoplasm)
62
List the five classes of steroid hormone.
Progestins,
androgens,
estrogens,
glucocorticoids,
mineralocorticoids
63
The monooxygenases involved in cholesterol and steroid hormone synthesis are part of what enzyme system?
The cytochrome P450 system
64
What are the three domains of any steroid hormone nuclear receptor?
1. A central DNA-binding region
2. A ligand-binding domain
3. A variable region (often regulatory)
65
What are the two types of steroid hormone nuclear receptor?
Cholesterol-derived (Type I)
Non-cholesterol-derived (Type II)
66
Which steroid hormone nuclear receptors are type I (cholesterol-derived)?
Estrogen receptor
Progesterone receptor
Glucocorticoid receptor
Mineralocorticoid receptor
67
Which steroid hormone nuclear receptors are type II (cholesterol-derived)?
Thyroxine receptor
Retinoic acid receptor
Vitamin D receptor
68
Where are type I steroid hormone receptors when not in-use?
Where are type II steroid hormone receptors when not in-use?
In the cytoplasm bound to an inhibitory ligand (often a heat-shock protein);
bound to DNA + a repressor
69
How many type I steroid hormone receptors does it take to initiate a change in gene expression?
2
(a pair of homodimers + coactivators + RXR sequence)
70
Type I steroid hormone receptors typically function as \_\_\_\_\_dimers.
Type II steroid hormone receptors typically function as \_\_\_\_\_dimers.
Homo-;
hetero-
71
What are the three receptor types that are typically clincally relevant in breast cancer?
**ER** (nuclear receptor)
**PR** (nuclear receptor)
**HER-****2/Neu** (receptor tyrosine kinase)
72
What drug can be used to block estrogen receptors in ER+ breast cancer?
Tamoxifen
73
What are the four main breast cancer classifications based on receptor types?
Endocrine receptor + (PR or ER)
HER-2/Neu +
Triple +
Triple -
74
Can tamoxifen be used to treat ER+ uterine endometrial carcinomas (UEC)?
**No**.
Tamoxifen is a selective ER modulator (SERM) and actually increases increases UEC growth.
(I.e. it blocks breast ERs but activates uterine ERs.)
75
Make the diagnosis:
## Footnote
* A 43 year old woman presents with a small area (1-2 cm) of increased density on her mammogram. She is a non-smoker, had her first child at 34 years, is pre-menopausal, and has no family history of cancer.*
* A mammogram shows areas of calcification (Figure 7, bottom left panel). A biopsy shows hyperplastic cells filling the mammary ducts (bottom right panel). There is central necrosis in these ducts, but the basement membrane is more or less intact.*
Ductal carcinoma in situ
76
What does HER-2 often become in breast cancer malignancies?
HER-2/Neu
| (Neu oncogene)
77
Tamoxifen increases risk of __________ cancer.
Uterine
78
In premenopausal women with ER+ breast cancer, tamoxifen is often warranted to combat the high estrogen effects at the breast.
What medication type might be used instead in a postmenopausal patient with ER+ breast cancer?
Aromatase inhibitors
79
What medication type can be used in prostate carcinomas to block the release of luteinizing hormone and testosterone and their effects on prostate epithelia?
(Note: this medication can also be used to treat ER+ breast cancer.)
Luteinizing Hormone Releasing Hormone (GnRH) analogs
(e.g. Lupron, Zoladex)
80
What medications can be used to treat prostate carcinoma by blocking the effects of testosterone at the prostate?
Flutamide;
casodex
81
**True/False**.
Monooxygenases are involved in the synthesis of cholesterol, bilirubin, vitamin C, steroid hormones, and the metabolism of glucose.
**False**.
Monooxygenases are involved in the synthesis of _bile acids_, vitamin _D_, steroid hormones, and the metabolism of _ethanol_.
82
Monooxygenases are also referred to as \_\_\_\_\_\_\_\_\_-function oxidases.
Essentially, they catalyze the oxygenation of _____________ and its derivatives, often using ________ as a cofactor.
Mixed;
cholesterol, NADPH
83
Describe the general reaction of a monooxygenase.
84
What are the two potential names for a monooxygenase that adds a hydroxyl group to the 7' carbon on cholesterol?
CYP7A1
7α-hydroxylase
85
Which ring of a precursor cholesterol will become aromatic in the synthesis of estrogens?
The A ring
86
In steroid hormone synthesis, cholesterol is first converted to \_\_\_\_\_\_\_\_\_\_\_\_\_, which then becomes \_\_\_\_\_\_\_\_\_\_\_\_\_\_, which can then become what three molecules?
Pregnenolone;
progesterone;
cortisol, aldosterone, OR, testosterone
87
**True/False**.
The synthesis of estrogens is the following:
Cholesterol --\> Pregnenolone --\> Progesterone --\> Estradiol
**False**.
Cholesterol --\> Pregnenolone --\> Progesterone --\> *Testosterone* --\> Estradiol
88
What cholesterol-derived steroid serves as the immediate precursor to glucocorticoids, mineralocorticoids, and androgens (and subsequently, estrogens)?
Progesterone
89
A deficiency of any of what four enzymes can result in **congenital adrenal hyperplasia**?
3-β-hydroxysteroid dehydrogenase
17-α-hydroxylase
21-α-hydroxylase
11-β-hydroxylase
*(also, 20,22-desmolase, but that is very rare)*
90
What enzyme converts cholesterol to pregnonelone?
What enzyme convers pregnonelone to progesterone?
20,22-**Desmolase**
(Cytochrome P450SCC)
**3-β-hydroxysteroid dehydrogenase**
91
**True/False**.
All steroid hormone can be created from progesterone.
True.
92
What enzyme is the rate-limiting step for all steroid synthesis?
What does it do?
20,22-**desmolase**
shortens the cholesterol hydrocarbon tail
93
Describe the effects that 3-β-hydroxysteroid has on pregnenolone.
94
**True/False**.
A deficiency of any of the following enzymes can produce congenital adrenal hyperplasia:
**20,22-Desmolase**
**4-β-hydroxysteroid dehydrogenase**
**18-β-hydroxylase**
**21-α-hydroxylase**
**12-α-hydroxylase**
**False**.
A deficiency of any of the following enzymes can produce congenital adrenal hyperplasia:
*20,22-Desmolase*
***3**-β-hydroxysteroid dehydrogenase*
***17-α**-hydroxylase*
*21-α-hydroxylase*
***11-β****-hydroxylase*
95
What are the effects of a 3-β-hydroxysteroid dehydrogenase deficiency?
Congenital adrenal hyperplasia;
## Footnote
**_no steroid hormone formation_**
*(i.e. no estrogens, androgens, glucocorticoids, or mineralocorticoids)*
96
What are the clinical effects of a 3-β-hydroxysteroid deficiency?
_No steroid hormone formation._
**Na+ loss**;
**adrenal hyperplasia**;
**cilitoromegaly** (females);
**ambiguous-to-female genitalia** (males);
97
What are the two weaker androgens?
Where are they expressed?
DHEA, androstenedione;
testis, overies, adrenal cortex
98
What are the four androgens according to potency?
What are the three estrogens according to potency?
Testosterone, DHT \> DHEA, androstenedione;
estradiol \> estrone \> estriol
99
What enzyme is the first step in conversion of progesterone to testosterone?
What enzyme is the second step in conversion of progesterone to testosterone?
**17-α-hydroxylase**
(CYP17A1);
3-β-hydroxysteroid dehydrogenase
100
What are the changes in synthesized steroid hormones seen in 17-α-hydroxylase deficiencies?
Lack of androgens, estrogens, and corticosteroids
+ **overproduction** of **mineralocorticoids**
101
What are the clinical effects of a 17- -hydroxylase deficiency?
Congenital adrenal hyperplasia;
**hypertension**
+
**hypernatremia** / **hypokalemia**
+
**male** **pseudohermaphroditism**
102
What two enzymatic effects does FSH have at the ovary?
1. Stimulation of _estradiol_ from _testosterone_ by **aromatase**
2. Stimulation of _estrone_ from _androstenedione_ by **aromatase**
103
What is(are) the major site(s) of estradiol production?
What is(are) the major site(s) of estrone production?
Ovaries;
skeletal muscle, adipose tissue
104
What are the three enzymes involved in converting progesterone to aldosterone?
21-α-hydroxylase
11-β-hydroxylase
Aldosterone synthase
105
Here are the enzymes of aldosterone synthesis from progesterone:
**21-α-hydroxylase**
**11-β-hydroxylase**
**Aldosterone synthase**
What are the two intermediates?
11-deoxycorticosterone;
corticosterone
106
What are the three enzymes involved in converting progesterone to cortisol?
17-α-hydroxylase
21-α-hydroxylase
11-β-hydroxylase
107
**True/False**
21-α-hydroxylase and 11-β-hydroxylase are both involved in the synthesis of mineralocorticoids AND glucocorticoids.
True.
108
Here are the enzymes involved in cortisol synthesis from progesterone:
**17-α-hydroxylase**
**21-α-hydroxylase**
**11-β-hydroxylase**
What are the two intermediates?
17-α-hydroxyprogesterone;
11-deoxycortisol
109
What is hydrocortisone (cortisone) (17-hydroxy-11-dehydrocorticosterone)?
How is it activated?
A cortisol precursor;
it is converted to cortisol via hydroxylation of C-11
110
What are the hallmarks of 3-β-hydroxysteroid dehydrogenase deficiency?
(What is missing? What are the clinical S/Sy?)
Congenital adrenal hyperplasia:
_no steroid synthesis_
**female genitalia**
**salt excretion**
111
What are the hallmarks of a 17-α-hydroxylase deficiency?
(What is missing? What are the clinical S/Sy?)
Congenital adrenal hyperplasia:
_no sex hormone or cortisol synthesis, BUT increased mineralocorticoids_
**female genitalia**
**Na+ retention / hypertension**
112
What are the hallmarks of a 21-α-hydroxylase deficiency?
(What is missing? What are the clinical S/Sy?)
Congenital adrenal hyperplasia:
_no aldosterone or cortisol synthesis, BUT increased androgens_
**masculinization/virilization**
**Na+ loss + hypotension**
113
What are the hallmarks of an 11-β-hydroxylase deficiency?
(What is missing? What are the clinical S/Sy?)
Congenital adrenal hyperplasia:
_no aldosterone or cortisol synthesis, BUT increased 11-deoxycorticosterone and androgens_
**masculinization/virilization**
**Na+ retention + hypertension**
114
What is the most common cause of congenital adrenal hyperplasia?
21-α-hydroxylase deficiency
115
Describe the main locations in steroid synthesis where congenital adrenal hyperplasia may result if enzymes are deficient.
116
An _11-β-hydroxylase deficiency_ is characterized by an increase in what steroid hormone intermediate that differentiates it from a _21-α-hydroxylase deficiency_?
What is the result?
11-deoxycorticosterone;
Na+ retention and hypertension
(compared to the hypotension and salt wasting in 21-α-hydroxylase deficiency)
117
How often are water-soluble vitamins (B and C) needed in our diets to maintain proper enzymatic functioning?
How often are fat-soluble vitamins (ADEK) needed in our diets to maintain proper enzymatic functioning?
Every 1 - 3 days;
weeks-to-months
118
What class of vitamin is more likely to be deficient in the human body?
What class of vitamin is more likely to reach toxic levels in the human body?
Water-soluble (B,C);
fat-soluble (ADEK)
119
What is the term describing the maximum expected concentration of a particular vitamin at which the human body is expected to not experience toxic side effects?
Tolerable upper intake (UI) levels
120
Thiamine (B1) is typically found as what cofactor in the body?
It is utilized in what type of reactions?
Thiamine pyrophosphate;
**dehydrogenase** **complexes** (PDH, α-ketoglutarate DH), **transketolases**
121
Identify the disorder described below:
a chronic alcoholic presents with edema and high-output cardiac failure.
What deficiency may be to blame?
Wet Beriberi;
thiamine
122
Identify the disorder described below:
a chronic alcoholic presents with muscle wasting, ataxia, and confusion.
What deficiency may be to blame?
Dry Beriberi;
thiamine
123
Identify the disorder described below:
a chronic alcoholic presents with amnesiatic memory loss, gait instability, and ophthalmoplegia.
What deficiency may be to blame?
Wernicke-Korsakoff syndrome;
thiamine
124
A newborn child is jaundiced and you make the diagnosis of hyperbilirubinemia.
What treatment do you start?
What is a potential side effect?
Phototherapy;
riboflavin (B2) deficiency (destroyed by UV rays)
125
What are the S/Sy of a riboflavin deficiency?
Inflamed eyelids and cornea, sensitivity to light, conjunctivitis;
sore throat, glossitis, seborrheic dermatitis, cheilosis
126
Riboflavin is used to make what cofactor?
FAD
(triple ring structure allows for electron carrying)
127
What cofactors are derived from niacin (B3)?
What are the S/Sy of a niacin deficiency?
**NAD**+ (dehydrogenase reactions), **NADP**+ (anabolic reactions);
pellagra (dermatitis, diarrhea, dementia),
abdominal pain, glossitis, apathy
128
What effects does niacin have as a medication?
What are some potential side effects?
Decreases cholesterol, increases HDL;
**flushing**, hives, liver damage, blurred vision
129
What cofactor is pantothenic acid used to synthesize?
**True/False**.
B5 deficiencies are extremely rare and difficult to diagnose.
CoA;
true
130
Vitamin B6 (pyridoxal, pyridoxine, and pyridoxamine) is necessary for the synthesis of what cofactor?
In what reaction types and examples is it involved?
Pyridoxal phosphate (PLP);
**transamination** (involved in the urea cycle, and amino acid metabolism);
**glycogen** **phosphorylase**;
**neurotransmitter** **synthesis** (e.g. γ-aminobutyric acid).
131
In what reaction types and examples is pyridoxal phosphate necessary?
**Transamination** (involved in the urea cycle, and amino acid metabolism);
**glycogen** **phosphorylase**;
**neurotransmitter** **synthesis** (e.g. γ-aminobutyric acid).
132
How do vitamin B6 deficiencies present (very rare)?
Scaly dermatitis, anemia (microcytic), depression, confusion, abnormal brain wave pattern, convulsions
133
How do vitamin B6 toxicities present?
Depression/fatigue/irritability, headaches;
nerve damage, convulsions, skin lesions.
134
Biotin (B7) is used in what type of reaction?
Caboxylation reactions
135
A patient presents with depression/lethargy and hallucinations, numb or tingling sensation in the arms and legs, a scaly rash around the eyes/nose/mouth, and hair loss.
You note that the patient often ingests raw eggs. What may be the issue?
Biotin deficiency
| (avidin from the egg binding biotin)
136
What cofactors are synthesized from folate (B9)?
What types of reactions does it facilitate?
Tetrahydrofolate, dihydrofolate;
methyl group transfer (notably, dUMP and dTMP synthesis)
137
What two vitamins activate one another and present similarly when deficient?
Folate and B12
138
Why should sexually active women of child-bearing age ensure adequate folate intake?
To decrease risk of fetal neural tube defects
139
How does folate protect against heart disease?
By aiding in homocysteine breakdown
140
What is the main sign of a folate or B12 deficiency?
How can they be distinguished?
What substance is elevated in both cases?
Macrocytic (megaloblastic) anemia;
if B12, methylmalonic acid will elecated;
homocysteine
141
Cobalamin (B12) is a cofactor in the catabolism of what substrates?
Odd numbered-chain FAs,
branched-chain amino acids,
threonine (e.g. methylmalonyl-CoA mutase)
142
Cobalamin (B12) is a cofactor in the conversion of __________ to ___________ via methionine synthase.
Homocysteine,
methionine
143
Name the respective cofactor (vitamin) associated with each of the following reaction types:
## Footnote
**Transaminase**
**Transketolase**
**Odd-number chain FA catabolism**
**Dehydrogenase complexes**
Pyridoxal phosphate (pyridoxal/pyridoxine/pyridoxamine, B6)
Thiamine pyrophosphate (B1)
Cobalamin (B12)
Thiamine pyrophosphate (B1)
144
Name the respective cofactor (vitamin) associated with each of the following reaction types:
**Methyl donation**
**Metabolism of carbohydrates, proteins, *and* lipids**
**Neurotransmitter synthesis** (e.g. γ-aminobutyric acid)
**Malate or lactate dehydrogenase**
Tetra- or dihydrofolate reductase (folate, B9)
CoA (pantothenic acid, B5)
Pyridoxal phosphate (pyridoxal/pyridoxine/pyridoxamine, B6)
NAD+ (niacin, B3)
145
Name the respective cofactor (vitamin) associated with each of the following reaction types:
**Carboxylation**
**Hydroxylation**
**Branched-chain amino acid catabolism**
**Fatty acid synthesis**
Biotin (B7)
Ascorbic acid (C)
Cobalamin (B12)
NADP+ (niacin, B3)
146
What are some of the substances that are hydroxylated with ascorbic acid (vitamin C) as a cofactor?
Proline (collagen formation),
carnitine,
dopamine (norepinephrine formation),
some hormones
147
Besides its role as cofactor in hydroxylation reactions, what are some of ascorbic acid's (vitamin C) other functions?
Antioxidant;
increased immune activity;
antihistamine
148
What are some of the S/Sy of scurvy?
**Swollen, bleeding gums**,
**pinpoint hemorrhages**,
**anemia**,
atherosclerotic disease (an increase in oxidized LDL),
poor wound healing,
bone fragility,
joint pain
149
A 67-year-old man presents at the ED with complaints of swollen gums, facial red marks, and joint pain (images attached). You note a poorly healed cut on his forearm; he reports that he accidentally sliced himself superficially a few weeks ago.
The man is homeless and describes a diet of mostly crackers, chicken, and infrequent beans.
**What is the diagnosis?**
Scurvy
| (ascorbic acid / vitamin C deficiency)
150
What are all the forms of vitamin A?
Retinoids (retinal, retinol, retinoic acid)
151
What is the relationship between carrots and vitamin A?
β-carotene can be converted to retinol in the gut
152
**True/False**.
Retinoic acid and retinol are interconvertable but not with retinal.
**False**.
Retinoic acid is made from retinal.
Retinol and retinal are readily interconvertable.
153
Absorption of light causes what conformational change in the eye?
What happens next?
11-cis-retinal to trans-retinal;
GPCR (rhodopsin) activation --\> signal transduction --\> sight
154
**True/False**.
Retinol is involved in the maintenance of various tissues, including mucous membranes, the repair of body tissue and blood, and the immune system (e.g. resistance to infection).
True.
155
What are some early S/Sy of vitamin A deficiency?
And chronic?
Night blindness, follicular hyperkeratosis, susceptibility to infection;
anemia, keratinization
156
**True/False**.
Calcitriol (vitamin D) and niacin (vitamin B3) are technically not vitamins.
**True**.
They can be naturally synthesized in the body.
157
Describe the synthesis of vitamin D precursors in the skin and subsequent formation of vitamin D.
**7-dehydrocholesterol** --\> *(UV light)* --\> **Cholecalciferol**
--\> *(hydroxylation in liver)* --\> **25-vitamin D** --\>
*(hydroxylation in kidney)* --\> **1,25-vitamin D**
158
What type of vitamin D precursor can be gained through ingesting plant products?
Ergocalciferol (cholecalciferol)
159
Above what latitude in the northern hemisphere is calcitriol synthesis severely decreased due to a decrease in sunlight?
And below what latitude in the southern hemisphere?
40° north;
40° south
160
What is calcitriol?
What is cholecalciferol (ergocalciferol)?
1,25-hydroxyvitamin D3;
inactive vitamin D3
161
What is another name for vitamin E?
α-tocopherol
162
Vitamin E deficiencies are very rare.
Where is vitamin E stored and what might be some S/Sy if an individual were deficient?
Fat;
hemolytic anemia, neuromuscular disorders
163
What are some effects of α-tocopherol (vitamin E) toxicity?
Decreased vitamins A, D, and K
hemorrhaging effects (interferes with vit. K _and_ enhances anti-coagulant medications)
164
What is another term for vitamin K?
Quinones
165
What clotting factors are synthesized from quinones (vitamin K)?
Factors II, VII, IX, and X;
proteins C and S
166
What enzyme activates vitamin K?
What medication inhibits this process?
Epoxide reductase;
warfarin (Coumadin)
167
What type of reaction is essential to the activation of vitamin K-derived clotting factors?
Carboxylation
168
Why are vitamin K deficiencies rare?
The gut flora synthesizes it
169
What are the effects of too much vitamin K?
No established side effects
170
What form of vitamin K comes from the gut flora?
What form of vitamin K comes from ingested leafy greens?
What form of vitamin K is synthetic and more water-soluble (digestible regardless of bile acids intestinal lipids)?
**K2** (menaquinone)
**K1** (phylloquinone)
**K**3 (menadione)
171
What populations are most at-risk for vitamin K deficiencies and subsequent hemorrhage?
Newborns (no gut flora);
adults on long-term antibiotics (decreased gut flora)
172
What is a simple way to remember the common order of enzymes in the adrenal cortex?
3,2,1
Desmolase --\> **3**β-HSD --\> **2**1β-H --\> **1**1β-H --\>
173
What is the order of enzymes in the adrenal glomerulosa?
- Desmolase
- 3β-hydroxysteroid dehydrogenase
- 21β-hydroxylase
- 11β-hydroxylase
- Aldosterone synthase
174
What is the order of enzymes in the adrenal fasciculata?
- Desmolase
- 17α-hydroxylase
- 3β-hydroxysteroid dehydrogenase
- 21β-hydroxylase
- 11β-hydroxylase
175
What is the order of enzymes in the adrenal fasciculata?
- Desmolase
- 17α-hydroxylase
- 7,20-lyase
- 3β-hydroxysteroid dehydrogenase
- 17β-hydroxysteroid dehydrogenase
176
Complete the following reactions performed by 3β-hydroxysteroid dehydrogenase:
Pregnenolone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_\_
17-hydroxypregnenolone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_\_
DHEA --\> \_\_\_\_\_\_\_\_\_\_\_\_\_\_
Pregnenolone --\> **_Progesterone_**
17-hydroxypregnenolone --\> **17-_hydroxyprogesterone_**
DHEA --\> **_Androstenedione_**
177
Complete the following reactions performed by 21β-hydroxylase:
Progesterone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_
17-hydroxyprogesterone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_
Progesterone --\> **_11-deoxycorticosterone_**
17-hydroxyprogesterone --\> **_11-deoxycortisol_**
178
Complete the following reactions performed by 11β-hydroxylase:
11-deoxycorticosterone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_
11-deoxycortisol --\> \_\_\_\_\_\_\_\_\_\_\_\_\_
11-deoxycorticosterone --\> **_Corticosterone_**
11-deoxycortisol --\> **_Cortisol_**
179
Complete the following reactions performed by 17α-hydroxylase:
Pregnenolone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_
Progesterone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_
Pregnenolone --\> **_17-hydroxypregnenolone_**
Progesterone --\> **_17-hydroxyprogesterone_**
180
Complete the following reactions performed by 17,20-lyase:
17-hydroxypregnenolone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_
17-hydroxyprogesterone --\> \_\_\_\_\_\_\_\_\_\_\_\_\_
17-hydroxypregnenolone --\> **_DHEA_**
17-hydroxyprogesterone --\> **_Androstenedione_**
181
What enzyme converts androstenedione to testosterone?
17β-hydroxysteroid dehydrogenase
182
How can this seemingly complex chart be simplified?
The progessive enzymes are in descending numerical order (**3**β-HSD --\> **2**1β**-**H --\> **1**1β-H);
enzymes with 17s (**17**α-H; **17**,20-L) allow for switching tracks
