Biochemistry - Endocrine / Reproductive Block Flashcards
Which organ is the main regulator of body cholesterol?
The liver
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?
Chylomicrons
VLDL
HDL
Which is the hydrophilic portion of a cholesterol molecule?
Which is the hydrophobic portion of a cholesterol molecule?
The 3’-OH
the rest of the molecule
True/False.
Cholesterol is a polar molecule made of 4 rings + a 7 carbon tail attached to the 18’-carbon.
False.
Cholesterol is a polar molecule made of 4 rings + an 8 carbon tail attached to the 17‘-carbon.
What is the initial precursor used to synthesize cholesterol?
Acetyl-CoA
Describe the basic steps (in simplified form) of cholesterol synthesis.
Acetyl-CoA + 3-carbon molecule –> 5-carbon isoprene
5 isoprenes –> 30-carbon squalene
Cyclization –> 27-carbon, 4-ring cholesterol
What are the major intermediates of cholesterol synthesis?
(18) Acetyl-CoA –>
(6) HMG-CoA –>
(6) mevalonate –>
(6) activated isoprene –>
(1) squalene –>
(1) cholesterol
Besides cholesterol, what other metabolites is activated isoprene (pentenyl pyrophosphate) potentially used to synthesize?
Vitamins ADEK,
dolichol (used in N-linked glycosylation),
quinone electron carriers
What is the substrate and product of the reaction mediated by HMG-CoA reductase?
HMG –> Mevalonate
How do statins inhibit HMG-CoA reductase?
Via what type of inhibition?
They are structural analogs;
competitive inhibition
The complex process of squalene cyclizing and hydroxyl groups being added to the subsequent cholesterol molecule is completed by enzymes known as _____________.
Monooxygenases
Describe the allosteric regulation of HMG-CoA reductase.
High ATP –> increased protein phosphatase activity –>
increased HMG-CoA reductase activity
Low ATP –> increased AMP-activated protein kinase (AMPK) activity –>
decreased HMG-CoA activity
For what purpose does high ATP levels stimulate HMG-CoA reductase activity?
A period of high ATP levels (e.g. the non-fasting state) is the time for membrane repair and compound synthesis
What effect does insulin have on HMG-CoA reductase?
What effect do glucagon/epinephrine have on HMG-CoA reductase?
Increased activity;
decreased activity
What effect does dephosphorylation have on HMG-CoA reductase?
What effect do phosphorylation have on HMG-CoA reductase?
Increased activity;
decreased activity
Describe the upregulation of HMG-CoA expression.
Low [cholesterol]:
SREBP-SCAP moves from the ER to the Golgi –>
SREBP moves to the nucleus and binds SRE –>
Transcription increases
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
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
Describe what happens after a chylomicron is formed in the enterocytes.
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
Describe the frunctions/relationship between VLDL and LDL.
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
What are the four main lipoprotein complexes?
Chylomicrons
VLDL
LDL
HDL
Name the basic function of each of the following lipoprotein complexes:
Chylomicron
Chylomicron remnant
VLDL
LDL
HDL
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
Describe the various relationships between the various lipoprotein complexes (chylomicrons, chylomicron remnants, VLDLs, LDLs, HDLs)
What is indicated by high LDL levels?
What is indicated by high HDL levels?
High cholesterol;
cholesterol being cleared from the periphery
List the four main lipoprotein complexes in order of increasing density.
Chylomicrons >
VLDLs >
LDLs >
HDLs
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)
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)
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
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)
What percentage of each of the following lipoprotein complexes is made up of triglycerides?
Chylomicrons
VLDLs
HDLs
85%
50%
4%
Name any intermediates in the synthesis of progesterone from cholesterol.
Cholesterol –> pregnenolone –> progesterone
After cholesterol is converted to pregnonelone and then progesterone, what three major pathways can it then follow?
Conversion to either:
glucocorticoids, mineralocorticoids, or testosterone
The corpus luteum is responsible for the synthesis of what major hormone(s)?
Progesterone,
estradiol
What effect do mineralocorticoids have on the kidneys?
Increased Na+ reabsorption;
increased K+/H+ excretion
What effect can anabolic steroids have on an individual’s lipid profile?
What class has the opposite effect?
Increased LDL, decreased HDL;
estrogens
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
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
What effect can anabolic steroid use during pregnancy have on a male fetus?
And a female fetus?
Female features;
male features
True/False.
Mineralocorticoids aid in the metabolism of carbohydrates, proteins, and lipids.
False.
Glucocorticoids aid in the metabolism of carbohydrates, proteins, and lipids.
True/False.
Glucocorticoids have opposing effects in the liver and in adipose tissue.
True.
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)
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)
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
True/False.
The insulin resistance in T2DM is at least partially due to elevated serum fatty acids inibiting proper glucose metabolism.
True.
What does the peroxisome proliferator-activated receptor γ do?
What class of medication activates this receptor?
Increases adipose phosphoenolpyruvate carboxykinase activity;
thiazolidinediones (glitazones)
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
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.
What particular effects may present in a newborn if cholesterol biosynthesis is disrupted during embryonic development?
Holoprosencephaly;
genitourinary abnormalities
What axis of the neural tube is abnormal in cases of holoprosencephaly?
Ventral-dorsal
True/False.
Holoprosencephaly may display a wide range of variability.
True
(anything from lethality to a single central incisor)
What genetic defect is often indicated in holoprosencephaly?
What is its inheritability?
SHH;
autosomal dominant
What neural effect will result if the SHH gene is disrupted during development?
Holoprosencephaly
What role does the SHH gene play in neural tube development?
Regulation of the ventral-dorsal axis
What lipid is necessary for proper functioning of the SHH gene?
What may result if this lipid is absent during development?
Cholesterol;
holoprosencephaly
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
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
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
What gene is likely affected by the cholesterol deficiency seen in Smith-Lemli-Opitz syndrome?
SHH
True/False.
Many disorders of cholesterol synthesis have accompanying adrenal and gonadal insufficiencies.
True.
What is desmosterolosis?
What is deficient?
What is the buildup product?
A disorder of cholesterol synthesis;
lack of cholesterol –> disrupted SHH action;
desmosterol
True/False.
Phospholipids are essential to normal SHH (Sonic the Hedgehog gene) function.
False.
Cholesterol is essential to normal SHH function.
Where are steroid hormone receptors located?
Intracellularly
(in the nucleoplasm, nuclear membrane, or cytoplasm)
List the five classes of steroid hormone.
Progestins,
androgens,
estrogens,
glucocorticoids,
mineralocorticoids
The monooxygenases involved in cholesterol and steroid hormone synthesis are part of what enzyme system?
The cytochrome P450 system
What are the three domains of any steroid hormone nuclear receptor?
- A central DNA-binding region
- A ligand-binding domain
- A variable region (often regulatory)
What are the two types of steroid hormone nuclear receptor?
Cholesterol-derived (Type I)
Non-cholesterol-derived (Type II)
Which steroid hormone nuclear receptors are type I (cholesterol-derived)?
Estrogen receptor
Progesterone receptor
Glucocorticoid receptor
Mineralocorticoid receptor
Which steroid hormone nuclear receptors are type II (cholesterol-derived)?
Thyroxine receptor
Retinoic acid receptor
Vitamin D receptor
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
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)
Type I steroid hormone receptors typically function as _____dimers.
Type II steroid hormone receptors typically function as _____dimers.
Homo-;
hetero-
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)
What drug can be used to block estrogen receptors in ER+ breast cancer?
Tamoxifen
What are the four main breast cancer classifications based on receptor types?
Endocrine receptor + (PR or ER)
HER-2/Neu +
Triple +
Triple -
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.)
Make the diagnosis:
- 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
What does HER-2 often become in breast cancer malignancies?
HER-2/Neu
(Neu oncogene)
Tamoxifen increases risk of __________ cancer.
Uterine
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
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)
What medications can be used to treat prostate carcinoma by blocking the effects of testosterone at the prostate?
Flutamide;
casodex
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.
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
Describe the general reaction of a monooxygenase.
What are the two potential names for a monooxygenase that adds a hydroxyl group to the 7’ carbon on cholesterol?
CYP7A1
7α-hydroxylase
Which ring of a precursor cholesterol will become aromatic in the synthesis of estrogens?
The A ring
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
True/False.
The synthesis of estrogens is the following:
Cholesterol –> Pregnenolone –> Progesterone –> Estradiol
False.
Cholesterol –> Pregnenolone –> Progesterone –> Testosterone –> Estradiol
What cholesterol-derived steroid serves as the immediate precursor to glucocorticoids, mineralocorticoids, and androgens (and subsequently, estrogens)?
Progesterone
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)
What enzyme converts cholesterol to pregnonelone?
What enzyme convers pregnonelone to progesterone?
20,22-Desmolase
(Cytochrome P450SCC)
3-β-hydroxysteroid dehydrogenase
True/False.
All steroid hormone can be created from progesterone.
True.
What enzyme is the rate-limiting step for all steroid synthesis?
What does it do?
20,22-desmolase
shortens the cholesterol hydrocarbon tail
Describe the effects that 3-β-hydroxysteroid has on pregnenolone.
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
What are the effects of a 3-β-hydroxysteroid dehydrogenase deficiency?
Congenital adrenal hyperplasia;
no steroid hormone formation
(i.e. no estrogens, androgens, glucocorticoids, or mineralocorticoids)
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);
What are the two weaker androgens?
Where are they expressed?
DHEA, androstenedione;
testis, overies, adrenal cortex
What are the four androgens according to potency?
What are the three estrogens according to potency?
Testosterone, DHT > DHEA, androstenedione;
estradiol > estrone > estriol
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
What are the changes in synthesized steroid hormones seen in 17-α-hydroxylase deficiencies?
Lack of androgens, estrogens, and corticosteroids
+ overproduction of mineralocorticoids
What are the clinical effects of a 17- -hydroxylase deficiency?
Congenital adrenal hyperplasia;
hypertension
+
hypernatremia / hypokalemia
+
male pseudohermaphroditism
What two enzymatic effects does FSH have at the ovary?
- Stimulation of estradiol from testosterone by aromatase
- Stimulation of estrone from androstenedione by aromatase
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
What are the three enzymes involved in converting progesterone to aldosterone?
21-α-hydroxylase
11-β-hydroxylase
Aldosterone synthase
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
What are the three enzymes involved in converting progesterone to cortisol?
17-α-hydroxylase
21-α-hydroxylase
11-β-hydroxylase
True/False
21-α-hydroxylase and 11-β-hydroxylase are both involved in the synthesis of mineralocorticoids AND glucocorticoids.
True.
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
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
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
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
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
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
What is the most common cause of congenital adrenal hyperplasia?
21-α-hydroxylase deficiency
Describe the main locations in steroid synthesis where congenital adrenal hyperplasia may result if enzymes are deficient.
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)
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
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)
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
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
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
Identify the disorder described below:
a chronic alcoholic presents with muscle wasting, ataxia, and confusion.
What deficiency may be to blame?
Dry Beriberi;
thiamine
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
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)
What are the S/Sy of a riboflavin deficiency?
Inflamed eyelids and cornea, sensitivity to light, conjunctivitis;
sore throat, glossitis, seborrheic dermatitis, cheilosis
Riboflavin is used to make what cofactor?
FAD
(triple ring structure allows for electron carrying)
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
What effects does niacin have as a medication?
What are some potential side effects?
Decreases cholesterol, increases HDL;
flushing, hives, liver damage, blurred vision
What cofactor is pantothenic acid used to synthesize?
True/False.
B5 deficiencies are extremely rare and difficult to diagnose.
CoA;
true
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).
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).
How do vitamin B6 deficiencies present (very rare)?
Scaly dermatitis, anemia (microcytic), depression, confusion, abnormal brain wave pattern, convulsions
How do vitamin B6 toxicities present?
Depression/fatigue/irritability, headaches;
nerve damage, convulsions, skin lesions.
Biotin (B7) is used in what type of reaction?
Caboxylation reactions
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)
What cofactors are synthesized from folate (B9)?
What types of reactions does it facilitate?
Tetrahydrofolate, dihydrofolate;
methyl group transfer (notably, dUMP and dTMP synthesis)
What two vitamins activate one another and present similarly when deficient?
Folate and B12
Why should sexually active women of child-bearing age ensure adequate folate intake?
To decrease risk of fetal neural tube defects
How does folate protect against heart disease?
By aiding in homocysteine breakdown
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
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)
Cobalamin (B12) is a cofactor in the conversion of __________ to ___________ via methionine synthase.
Homocysteine,
methionine
Name the respective cofactor (vitamin) associated with each of the following reaction types:
Transaminase
Transketolase
Odd-number chain FA catabolism
Dehydrogenase complexes
Pyridoxal phosphate (pyridoxal/pyridoxine/pyridoxamine, B6)
Thiamine pyrophosphate (B1)
Cobalamin (B12)
Thiamine pyrophosphate (B1)
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)
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)
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
Besides its role as cofactor in hydroxylation reactions, what are some of ascorbic acid’s (vitamin C) other functions?
Antioxidant;
increased immune activity;
antihistamine
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
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)
What are all the forms of vitamin A?
Retinoids (retinal, retinol, retinoic acid)
What is the relationship between carrots and vitamin A?
β-carotene can be converted to retinol in the gut
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.
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
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.
What are some early S/Sy of vitamin A deficiency?
And chronic?
Night blindness, follicular hyperkeratosis, susceptibility to infection;
anemia, keratinization
True/False.
Calcitriol (vitamin D) and niacin (vitamin B3) are technically not vitamins.
True.
They can be naturally synthesized in the body.
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
What type of vitamin D precursor can be gained through ingesting plant products?
Ergocalciferol (cholecalciferol)
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
What is calcitriol?
What is cholecalciferol (ergocalciferol)?
1,25-hydroxyvitamin D3;
inactive vitamin D3
What is another name for vitamin E?
α-tocopherol
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
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)
What is another term for vitamin K?
Quinones
What clotting factors are synthesized from quinones (vitamin K)?
Factors II, VII, IX, and X;
proteins C and S
What enzyme activates vitamin K?
What medication inhibits this process?
Epoxide reductase;
warfarin (Coumadin)
What type of reaction is essential to the activation of vitamin K-derived clotting factors?
Carboxylation
Why are vitamin K deficiencies rare?
The gut flora synthesizes it
What are the effects of too much vitamin K?
No established side effects
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<strong>3</strong> (menadione)
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)
What is a simple way to remember the common order of enzymes in the adrenal cortex?
3,2,1
Desmolase –> 3β-HSD –> 21β-H –> 11β-H –>
What is the order of enzymes in the adrenal glomerulosa?
- Desmolase
- 3β-hydroxysteroid dehydrogenase
- 21β-hydroxylase
- 11β-hydroxylase
- Aldosterone synthase
What is the order of enzymes in the adrenal fasciculata?
- Desmolase
- 17α-hydroxylase
- 3β-hydroxysteroid dehydrogenase
- 21β-hydroxylase
- 11β-hydroxylase
What is the order of enzymes in the adrenal fasciculata?
- Desmolase
- 17α-hydroxylase
- 7,20-lyase
- 3β-hydroxysteroid dehydrogenase
- 17β-hydroxysteroid dehydrogenase
Complete the following reactions performed by 3β-hydroxysteroid dehydrogenase:
Pregnenolone –> ______________
17-hydroxypregnenolone –> ______________
DHEA –> ______________
Pregnenolone –> Progesterone
17-hydroxypregnenolone –> 17-hydroxyprogesterone
DHEA –> Androstenedione
Complete the following reactions performed by 21β-hydroxylase:
Progesterone –> _____________
17-hydroxyprogesterone –> _____________
Progesterone –> 11-deoxycorticosterone
17-hydroxyprogesterone –> 11-deoxycortisol
Complete the following reactions performed by 11β-hydroxylase:
11-deoxycorticosterone –> _____________
11-deoxycortisol –> _____________
11-deoxycorticosterone –> Corticosterone
11-deoxycortisol –> Cortisol
Complete the following reactions performed by 17α-hydroxylase:
Pregnenolone –> _____________
Progesterone –> _____________
Pregnenolone –> 17-hydroxypregnenolone
Progesterone –> 17-hydroxyprogesterone
Complete the following reactions performed by 17,20-lyase:
17-hydroxypregnenolone –> _____________
17-hydroxyprogesterone –> _____________
17-hydroxypregnenolone –> DHEA
17-hydroxyprogesterone –> Androstenedione
What enzyme converts androstenedione to testosterone?
17β-hydroxysteroid dehydrogenase
How can this seemingly complex chart be simplified?
The progessive enzymes are in descending numerical order (3β-HSD –> 21β-H –> 11β-H);
enzymes with 17s (17α-H; 17,20-L) allow for switching tracks
