Hormones I Flashcards
Which hormones require neural stimulation for them to be released? A. Epinephrine B. Norepinephrine C. Renin D. A and B E. AOTA
D. AOTA
Which of the following characterizes Neural Communication and NOT hormonal? A. Short term effects B. No voluntary control C. Mobile messages D. Slow onset of action
A. Short term effects
Neural communications are:
- fixed communication system
- have fast onset of action
- have short term effects
- partially voluntary (e.g. muscle cotnraction)
A cell with the ability to bind selectively a given hormone via a cognate receptor
Target cell
A factor determining concentration of hormone at target cell in relation to its dissociation constant:
Affinity with specific plasma proteins
Factors affecting hormone concentration at target cell in relation to dilution effect:
Proximity of the target cell to hormone source
Which of the following affects the actual response of the target cell to the hormone?
A. Affinity of the hormone to plasma protein
B. Proximity of the target cell to the hormone source
C. Metabolism of the hormone in the target cell
D. Rate of clearance of hormone from the plasma
E. Conversion of inactive or sub-optimally active forms of the hormone into the fully active form
C. Metabolism of the hormone in the target cell
The rest of the choices are factors affecting the hormone CONCENTRATION
Which of the following is not a factor affecting the actual response of the target cell to the hormone?
A. Number, relative activity and state of occupancy of the specific receptors
B. Rate of synthesis and secretion of hormone
C. Presence of factors within the cell that are necessary for hormone response
D. Up or down regulation of the receptor upon ligand interaction
E. Post-receptor desensitization
B. Rate of synthesis and secretion of hormone
Cell-associated recognition molecules that are proteins in nature exhibiting a high degree of specificity and discrimination of a hormone
Receptors
Which of the following is an important biochemical feature for hormone-receptor interaction?
A. Binding should be specific
B. Binding should be saturable
C. Binding should occur within the concentration range of the expected biological response
D. Binding is displaceable by agonist or antagonist
E. AOTA
E. AOTA (Harper 499)
Which of the following is true?
A, Glucocorticoid hormones directly enter the nucleus
B. Thyroid hormones and retinoic acid encounter their cognate receptor in the cytoplasm
C. With thyroid receptors, ligand binding results in dissociation of coactivator complex from the receptor
D. Cognate heterodimeric receptors of thyroid hormones are already bound to the appropriate response elements
E. Glucocorticoid receptor exists in a complex with hsp60
D. Cognate heterodimeric receptors of thyroid hormones are already bound to the appropriate response elements
Glucocorticoid hormones (solid triangles) encounter their cognate receptor (GR) in the cytoplasm, where GR exists in a complex with a chaperone protein, heat shock protein 90 (hsp).
By contrast, thyroid hormones
and retinoic acid directly enter the nucleus, where their cognate heterodimeric receptors are already bound to the appropriate response elements with an associated transcription corepressor complex. Ligand binding results in dissociation of the corepressor complex from the receptor, allowing an activator complex, consisting of the TR-TRE and coactivator, to assemble.
Receptors of no known ligands are called:
Orphan receptors
Which hormone receptor types are members of a large super family of nuclear receptors?
Steroid and Thyroid type
Liver cells have more than one receptor. Which of the following is NOT a hormone that target the liver cells? A. Glucagon B. Insulin C. Thyroxine D. Epinephrine E. Cortisol
C. Thyroxine
This accurately describes the relation of ligand to target cell:
A. One ligand can affect different cell types.
B. More than one ligand can affect a single cell type.
C. One ligand can exert many different effects in one or more target cells.
D. Many different molecules circulate in the extracellular fluid, but only a few are recognized by hormone receptors
E. AOTA
E. AOTA
Which of the following does not characterize a hormone?
A. High affinity for a receptor
B. Irreversible binding
C. No additive effect once all receptors are occupied
D. Occur within a concentration of the expected biological response
E. Specific and Saturable
B. (should be reversible)
C. is the definition of saturable
D. is the definition of specific
What are the functional domains of receptors?
Recognition and Coupling domain
Which functional domain of a receptor is responsible for signal transduction? A. Extracellular domain B. Recognition Domain C. Coupling Domain D. Ligand domain E. NOTA
C. Coupling domain
Which of the following is NOT true of the coupling domain?
A. the transmembrane portion
B. faces the cytoplasm
C. couples hormone recognition with some intracellular function
D. binds the hormone
E. for receptor-effector coupling
D. (function of recognition domain)
Which of the following is NOT true of the coupling domain?
A. the transmembrane portion
B. faces the cytoplasm
C. couples hormone recognition with some intracellular function
D. binds the hormone
D. is for recognition domain
Which of the two classes of receptors generates signals that regulate various intracellular functions?
Membrane or Cell surface receptors
(Intracellular receptors provide signals to specific genes to affect rate of transcription via genomic activation or silencing)
Which of the following DOES NOT characterize cell surface receptors? A. can close or open channels B. can regulate protein synthesis C. can inactivate enzymes D. can affect cytoskeletal proteins E. NOTA
B. is a function of intracellular receptors via regulation of gene transcription
Which of the following DOES NOT utilize intracellular receptors? A. IGF-1 B. cortisol C. vitamin A D. thyroxine E. vitamin D
A. IGF-1 (a hydrophilic hormone; note that although it’s Group II, it requires transport protein)
IGF-1 (Jak-Stat pathway), insulin (tyrosine kinase), Protein, polypeptide and catecholamines (GPCR) utilize membrane/ cell surface receptors
This dual function mechanism provides the first step in amplification of the hormonal response
Receptor-effector coupling
The α subunit of the G protein includes which characteristic? A. ATPase activity B. Hydrolytic activity C. GTPase activity D. K+ channel stimulation E. PLC activation
C. GTPase activity
D and E:
The βγ complexes have been associated with K+ channel stimulation and phospholipase C activation. (Harper 522)
A phosphodiesterase can terminate response by converting cAMP to: A. ADP B. 3'-ADP C. 5'-AMP D. ATP E. 3'-AMP
C. 5’-AMP
PKA exists in an inactive form as: A. R2C2 heterotetramer B. R1C1 heterodimer C. RaRb homodimer D. RaCa homodimer E. NOTA
A. R2C2 heterotetramer
PKA exists in an inactive form as an R2C2 heterotetramer consisting of two regulatory (R) and two catalytic (C) subunits.
Which subunit of PKA, with the presence of cAMP, is activated after dissociation?
Catalytic subunits
Which of the following is a function of activated PKA?
A. converts proteins to phosphoprotein
B. phosphorylates proteins at Ser and Thr residues
C. removes phosphates from Ser and Thr residues
D. Both A and B
E. AOTA
D.
The active catalytic subunits [of PKA] phosphorylate a number of target proteins on serine and threonine residues [with Mg++ and ATP]. Phosphatases remove phosphate from these residues and thus terminate the physiologic response.
IGF-1 activates which signaling pathway?
Jak-Stat pathway
Polypeptides and Catecholamines utilizes which specific type of receptor?
GPCR
Insulin utilizes which specific type of receptor?
Tyrosine kinase (Class II: Cysteine family)
Which receptor subunit serves as hormone-binding domain for insulin? A. Alpha subunits B. Beta subunits C. Gamma subunits D. Delta subunits E. Epsilon subunits
A. Alpha subunits
Which receptor subunit serves as ATP-binding domains for insulin? A. Alpha subunits B. Beta subunits C. Gamma subunits D. Delta subunits E. Epsilon subunits
B. Beta subunits
Autophosphorylation of intracellular enzymes as instigated by insulin binding will activate which signaling pathway?
A. Phosphoinositide 3-kinase pathway
B. Mitogen-activated protein kinase pathway
C. Janus kinase pathway
D. Both A and B
E. AOTA
D.
→ Activates PI-3K signaling pathway that will cause the exteriorization of GLUT4
→ Activates MAP Kinase signaling pathway (mitogenic effects) which will phosphorylate certain proteins, or activate certain translation factors which will cause cell growth and gene expression via protein synthesis
Which of the following is included in the domains of Group I hormone receptors?
A. Domain responsible for hormone binding
B. Domain that binds to specific DNA sequences
C. Site that interacts with coregulator proteins
D. Domain that specifies binding to proteins that influence intracellular trafficking of receptor
E. AOTA
E. AOTA
What class of hormone (based on chemical composition) is calcitriol?
Steroid hormone
Amino acid derivative hormones are synthesized from the amino acid:
Tyrosine
2 Hormones derived from Tyr:
Catecholamines
Thyroid hormones
Glycoprotein hormones are:
A. Homodimer
B. Heterodimer
B. Heterodimer
Same α subunit but different β subunit
- FSH, LH, CG and TSH
The α-GSU is common to TSH, FSH, and LH, whereas the β subunit is specific to the hormone (i.e., β-TSH, β-FSH, and β-LH are all unique).
Class (by chemical composition) of Anterior pituitary hormones
Peptide/Protein hormones
Histamine is derived from which amino acid?
A. His
B. Trp
C. Tyr
A. Histidine
Serotonin is derived from which amino acid?
A. His
B. Trp
C. Tyr
B. tryptophan
Melatonin is derived from which amino acid?
A. His
B. Trp
C. Tyr
B. tryptophan
Which of the following hormones are derived from fatty acids? A. Prostaglandins B. Prostacyclins C. Thromboxanes D. Leukotrienes E. AOTA
E. AOTA
What is the intracellular messenger of Group I hormones?
Hormone-receptor complex itself
Group (by solubility property) of Eicosanoids
Group II
Location of receptors for lipid soluble ligands
A. On the outer surface of the plasma membrane
B. On the inner surface of the plasma membrane
C. On Organelles
C. On Organelles
Location of Receptors for intracellular signaling
A. On the outer surface of the plasma membrane
B. On the inner surface of the plasma membrane
C. On Organelles
B. On the inner surface of the plasma membrane
Receptors for water soluble ligands
A. On the outer surface of the plasma membrane
B. On the inner surface of the plasma membrane
C. On Organelles
A. On the outer surface of the plasma membrane
For group II hormones can be further subdivided into four groups. What is the group for those with kinases of phosphate cascade as their 2nd messengers?
Group IID
For group II hormones can be further subdivided into four groups. What is the group for those with cGMP as their 2nd messengers through guanylyl cyclase?
Group IIB
For group II hormones can be further subdivided into four groups. What is the group for those with calcium ion and phosphatidylinositol as their 2nd messengers through Phospholipase C?
Group IIC
Which of the following does not utilize cAMP as second messenger? A. α1-adrenergic catecholamines B. a2-adrenergic catecholamines C. B-adrenergic catecholamines D. calcitonin E. Chorionic gonadotropin, human (CG)
A. α1-adrenergic catecholamines (calcium or phosphatidylinositols (or both))
Which of the following does not utilize calcium or phosphatidylinositols (or both) as second messenger? A. Oxytocin B. Platelet-derived growth factor (PDGF) C. Substance P D. Thyrotropin-releasing hormone (TRH) E. Prolactin
E. Prolactin (kinase or phosphatase cascade)
Which of the following does not utilize kinase or phosphatase cascade as second messenger? A. Adiponectin B. Leptin C. CCK D. Erythropoietin E. Chorionic somatomammotropin
C. CCK (Ca++ or PI3)
Anterior pituitary hormones that do not belong to Group IIA:
GH and Prolactin (Group IID)
ADH belongs to which groups of hormone according to receptor location?
Groups IIA and IIC
Which growth factor belongs to Groups IIC and IID
Platelet-derived Growth Factor
Final organ to produce active form of Vitamin D
Kidneys
storage location of catecholamines
chromaffin granules
Conversion of testosterone to its active form (DHT) happens in which organs?
skin and prostate
Which of the following do not have intracellular reservoir? A. Steroid hormones B. Thyroid hormones C. Catecholamines D. Insulin
A. Steroid hormones
Thyroid hormones – stored for weeks
Catecholamines and PTH – hours
Insulin – several days
Hormones bound to transport proteins are not recognized by which enzymes in the liver?
Cytochrome enzymes for degradation
This represents the
circulating reservoir for hormones
Transport proteins
True or False:
When hormones are bound to transport proteins – they are inactive
True
Which thyroid hormone has a higher affinity to transport
proteins?
T4
Which thyroid hormone is more potent?
T3
Main androgen in the zona reticularis
DHEA
A small percentage of steroid hormone is produced in situ from:
Acetyl-CoA via mevalonate and squalene
During storage, free cholesterol is esterified to cholesterol ester once inside cytoplasm by which enzyme?
Acetyl-CoA acyltransferase
Enzyme that converts cholesterol ester to free cholesterol
Cholesterol ester hydrolase (esterase)
The rate-limiting step for steroidogenesis
ACTH-dependent diffusion of free cholesterol into the mitochondria by uptake of StAR (steroidogenic acute
regulatory) protein
Pregnenolone production is catalyzed by: A. CYP11A1 B. P450scc C. CYP17 D. Either A or B E. NOTA
D.
The action of P450scc on cholesterol is
A. sequential hydroxylation at C21 and C20
B. sequential hydroxylation at C22 and C20
C. sequential hydroxylation at C22 and C21
D. sequential hydroxylation at C21 and C23
B. sequential hydroxylation at C22 and C20
Which of the following is not an effect of estrogen? A. Increases vasodilation B. Increases HDL synthesis C. Activates Lipoprotein lipase D. Cell proliferation
C. should be Hormone-sensitive lipase
2 hormones that increase the receptors for LH
FSH and estrogen
These enzymes for mineralocorticoid synthesis are only found in the zona glomerulosa
18-hydroxylase
18-hydroxysteroid dehydrogenase
These are the most potent regulators of aldosterone
K+ levels and Angiotensin II
These are mitochondrial enzymes encountered by pregnenolone to convert it to progesterone
3β-hydroxysteroid dehydrogenase (converts to ketone)
and
Δ5,4-isomerase (transfers double bond from C5 to C4)
This adrenal cortical enzyme has both glucocorticoid and mineralocorticoid activity
21-hydroxylase (converts progesterone/17-hydroxyprogesterone to 11-DOC
A mitochondrial enzyme that converts 11-DOC to corticosterone
11β-hydroxylase
What are the enzymes required for glucocorticoid synthesis?
17-, 21-, 11β-hydroxylases
The action of this enzyme on pregnenolone will set the path of steroidogenesis to glucocorticoid synthesis
17α-hydroxylase (attaches a hydroxyl group at C17 to yield 17-hydroxypregnenolone)
The main transport protein for glucocorticoids
Cortisol-binding globulin (Transcortin)
the other is albumin
Hormone that increases the synthesis of CBG in the liver
Estrogen
Steroid hormones that will bind with high affinity on CBG
DOC (deoxycorticosterone) and Progesterone
Steroid that weakly binds with CBG
Gonadal steroids:
Estradiol, estrone, testosterone, DHT
DHEA being acted on by 3β-HD and Δ5,4-Isomerase will yield the more potent:
Androstenedione
This double-function enzyme converts the pregnenolone to the major androgen, DHEA
17-hydroxylase (with 17, 20-lyase function)
Enzyme that converts Androstenedione into Testosterone in the testis
17β-hydroxysteroid dehydrogenase
2 pathways for testicular steroidogenesis:
Progesterone (Delta-4 pathway) and
DHEA (Delta-5 pathway)
Which enzyme will set the path of testicular steroidogenesis to delta-4 pathway?
3β-HD and Δ5,4-isomerase
The predominant pathway of testicular steroidogenesis
Delta-5 or DHEA pathway
What reaction inactivates Testosterone? A. Oxidation of C17 B. Reduction of C17 C. Oxidation of the A-ring double bond D. Reduction of the A-ring double bone
A. Oxidation of C17
Conversion of Testosterone to the more potent Dihydrotestosterone (DHT) is by the action of the enzyme:
5α-reductase (NADPH-dependent)
Precursor for the most potent type of estrogen
Testosterone
precursor to 17β-estradiol
Precursor to the post-menopausal type of estrogen
Androstenedione (precursor to estrone)
This is the estrogen of adrenal origin
Estrone
The estrogen of pregnancy is produced by the:
placenta
What catalyzes the formation of estrogens via peripheral aromatization of androgens
Aromatase Enzyme Complex
The synthesis of estrogen from androgens requires the following, except: A. 3 hydroxylation steps B. Oxygen C. NADPH D.NADH E. Aromatase Enzyme Complex
D. NADH
Which cells of the ovary is the Aromatase Enzyme Complex found?
Granulosa cells
What enzyme is produced by the placenta to convert estrone to estriol?
16α-hydroxylase
Cell source of testosterone and androstenedione in Female
Theca cells
Which of the following organs is not a source of aromatase? A. Liver B. Skin C. Adipose tissue D. Uterus E. Breast
D. Uterus
In which structure is the progesterone the end product due to its lack of enzymes for the progression of steroidogenesis?
Corpus luteum
Hormone that increases the production of Sex Hormone Binding Globulin
Estrogen
True or False:
TEBG has higher affinity to estrogen than testosterone
False:
Testosterone-Estrogen Binding globulin has higher affinity with testosterone
Which hormone helps the body absorb calcium from the GIT?
Calcitriol
Between a light and dark-skinned individual, who has more Vitamin D?
Lighter skinned because melanin shields the skin from UV rays
Precursor of Vitamin D3 produced with exposure to UV light
7-dehydrocholesterol
Which liver enzyme converts cholecalciferol to 25-hydroxycholecalciferol?
NADPH-dependent cytochrome P450 reductase and CytP450
Vitamin D3-25-hydroxylase
Which renal enzyme converts 25-hydroxycholcalciferol to the active form of Vitamin D?
1α-hydroxylase
The predominant form of Vitamin D in the plasma
25-hydroxycholecalciferol or Vitamin D3
The active form of vitamin D
1,25-dihydroxycholecalciferol or Calcitriol
Calcitriol will increase absorption of which substances in the intestine? (2) answers
Calcium and Phosphate
In which layer/s of the epidermis is the 7-dehydrocholesterol found?
Malpighian layer of the epidermis
In which organelle does the conversion of Vit D3 to 25(OH)-D3 occur?
ER
The following is required in the conversion of D3 to 25(OH)-D3, except: A. Fe++ B. Mg++ C. NADPH D. O2 E. uncharacterized cytoplasmic factor
A. Fe++
In which organelle does the conversion of 25(OH)-D3 to calcitriol occur?
mitochondria
hydroxylation of C1
What are the enzymes involved in the final step of calcitriol synthesis?
Renal Ferredoxin reductase (flavoprotein) Renal Ferredoxin (Iron-sulfur protein) Cytochrome P450
The major adrenal medulla product
Epinephrine
Catecholamines are derived from which amino acid?
Tyrosine
Which of the following is the correct sequence of catecholamine synthesis?
A. Side chain hydroxylation > Ring hydroxylation > Side chain decarboxylation > Side chain N-methylation
B. Ring hydroxylation > Side chain decarboxylation > Side chain hydroxylation > Side chain N-methylation
C. Side chain N-methylation > Side chain hydroxylation > Ring hydroxylation > Side chain decarboxylation
B. Ring hydroxylation > Side chain decarboxylation > Side chain hydroxylation > Side chain N-methylation
The rate-limiting enzyme of catecholamine synthesis
Tyrosine hydroxylase
Cofactor needed in the first step of catecholamine synthesis
Tetrahydrobiopterin
The first 2 steps of catecholamine synthesis occur in which part of the chromaffin cell?
cytoplasm
The decarboxylation of side chain in catecholamine biosynthesis requires which coenzyme?
Pyridoxal phosphat
The decarboxylation of side chain in catecholamine biosynthesis requires which coenzyme?
Pyridoxal phosphate
The last 2 steps of catecholamine synthesis occur in which compartment of the chromaffin cells?
chromaffin granules
the action of dopamine-β-hydroxylase requires which compounds?
Ascorbate
Copper
Fumarate
Modulator compound in the synthesis of NE
Fumarate
Compound found in the active site of the enzyme responsible for the formation of NE
Copper
Electron donor in the production of NE
Ascorbate
Which hormone promotes the conversion of NE to Epinephrine?
Cortisol
Enzyme activated by the stimulation of cortisol to produce EPI
Phenylethanolamine-N-methyltransferase (PNMT)
Which enzyme is inhibited by the presence of epinephrine?
tyrosine hydroxylase
The degradation of catecholamines is catalyzed by which enzymes?
Monoamine oxidase and
Catechol-O-methyltransferase (COMT)
The end product of catecholamine degradation
vanillylmandelic acid (VMA)
Which product is expected to increase in the urine with pheochromocytoma?
VMA
The glycosylated protein precursor of thyroid hormones
thyroglobulin
The majority of iodine in thyroglobulin are found in its inactive precursors:
Monoiodotyrosine and Diiodotyrosine
Stimulation by ___ increases all aspects of thyroid hormone biosynthesis
Thyroid Stimulating Hormone
The prohormone released by the thyroid gland
Thyroxine
Which of the 2 thyroid hormones has higher affinity to transport proteins?
Thyroxine (T4)
This is considered as the active thyroid hormone
Triiodothyronine
The peripheral deiodinase is found in the following organs except: A. Pituitary B. Parathyroid gland C. Liver D. Kidneys E. NOTA
B. Parathyroid gland
The sequential steps to Thyroid Hormone Biosynthesis
Iodide trapping > Oxidation of Iodide to Iodine > Organification/Iodination of Tyr residues in thyroglobulin > Coupling/ Conjugation
Which of the following is not a peptide hormone? A. Insulin B. PTH C. Angiotensin D. LPH E. NOTA
E. NOTA
This is the 15 hydrophobic amino acids at the N-terminal of the insulin
Leader sequence/ signal sequence
In the ER, removal of the signal sequence in insulin biosynthesis will result to the product:
preinsulin
The 2 amino acids in the site-specific cleavage sites of proinsulin
Arginine and Lysine
How many amino acids form the A and B chain of insulin, respectively? A. 20, 31 B. 21, 30 C. 22, 33 D. 23, 40
B. 21 - A chain; 30 - B chain
The intradisulfide chain of insulin is found at: A. amino acid 5-15 of B chain B. amino acid 7-14 of B chain C. amino acid 19-20 of A chain D. amino acid 6-11 of A chain
D. amino acid 6-11 of A chain
Where are the interdisulfide chains of isulin found?
- between amino acid 7 (B chain) and 7 (A chain)
- between amino acid 19 (B chain) and 20 (A chain)
This conformation allows the formation of critical structures within insulin for it to reach maturity
INTRA and INTER chain disulfide links
Primary gene product in PTH biosynthesis
Prepro-PTH
Immediate precursor of PTH
Pro-PTH
The synthesis and secretion of PTH are regulated by:
Plasma ionized calcium levels
Calcium molecules attach to ________ in Parathyroid gland surface, which allows this protein to monitor and regulate the amount of calcium in the blood
Calcium-sensing receptor
The full biologic activity site of PTH is numbered:
1-34 residue
The region for receptor binding sites of PTH is numbered:
24-34
The PTH site-specific cleavage sites are marked by which amino acids?
Arginine, Lysine and Valine
Which cells of the kidney produce Renin?
Juxtaglomerular cells at the afferent arteriole
Which of Angiotensin is a decapeptide or an octapeptide?
Decapeptide = Ang I Octapeptide = Ang II
Which enzyme of the lungs cleaver Ang I to Ang II?
Angiotensin Converting Enzyme
How does Angiotensin II stimulate aldosterone
synthesis
Activates cAMP to increase conversion of cholesterol to pregnenolone via Cyt 11A1 and conversion of corticosterone to 18-hydroxycorticosterone via 18-hydroxylase
Which alpha-2-globulin produced by the liver is cleaved by a proteolytic enzyme from the kidneys in response to decreased blood pressure?
Angiotensinogen (alpha-2-globulin produced by the livers)
Renin (proteolytic enzymes produced by the kidneys)
Class of anti-hypertensive drugs: Captopril, Lisinopril
ACE-inhibitors
Class of anti-hypertensive drugs: Losartan
Angiotensin II receptor blockers
The long polypeptide chain, located in the anterior and intermediate lobes of the pituitary, that consists of peptides that act as hormones and neurotransmitters
Proopiomelanocortin
Hormones that come from POMC
ACTH, LPH, MSH
Neurotransmitters that come from POMC
Enkephalins and Endorphins
POMC has how many amino acids?
285
Which of the following does not have POMC? A. brain B. placenta C. reproductive tract D. GIT E. lungs
None of those
The amino-terminal fragment of POMC produces which Hormone?
gamma-MSH
What hormone and peptide is generated from cleavage of ACTH?
alpha-MSH: hormone
Corticotrophin-like Intermediate Peptide (CLIP): peptide
Which POMC fragment is the source of β-MSH
β-Lipotropin cleaved to form the C-terminal of γ-Lipotropin
Cleavage of β-Lipotropin fragments will produce
γ-Lipotropin and β-Endorphin
β-Endorphin is the source of which neurotransmitter?
Met-enkephalin
Which facilitates the proximation of disulfide chains of active insulin? a. Leader sequence b. C peptide c. Disulfide bonds itself d. Formation of pro-insulin
d. Formation of pro-insulin
