BIOCHEMISTRY OF PROTEIN (AMINO ACID HORMONES)

1. Characterize the hormone that is lacking in patients with Type 1 DM and discuss how it
is synthesized and secreted.

● INSULIN - a polypeptide of A & B chains linked by 2 inter and intrachain disulfide

(SH-HS) bridges
● A chain is composed of 21 amino acids // B chain is composed of 30 amino acids
● Interchain disulfide bonds at A7-B7 and A20-B19
● Zinc complexes with insulin as well as proinsulin
● Conserved positions which constitute the active region are:
○ 3 disulfide bonds
○ Hydrophobic residues in the COOH terminal regions of the B chain
○ NH3 and COOH terminals of the A chain

● SYNTHESIS AND SECRETION

○ PREPROINSULIN (preprohormone) - 23 amino acid hydrophobic leader
sequence directs it to ER
○ PROINSULIN (prohormone) - removed leader sequence; composed of A
& B chains linked by C (connecting) peptide; proinsulin goes to Golgi for
further proteolysis
○ INSULIN - endoproteolysis of the C peptide results to formation of mature
insulin (C peptide has no known biologic activity)
○ 40-50 units of Insulin are secreted daily by the Beta cells of the Pancreas
and is also equal to 15-20% of the gland’s stored hormone
○ Release is mediated by an elevation of plasma glucose (from fasting
levels of 80-100 mg/dL to 300-500 mg/dL postprandial)

2. Explain why Hansel was given 2 kinds of insulin and is from human endogenous insulin

● Marketed as the brand name product Humalog, insulin lispro begins to exert its effects
within 15 minutes of subcutaneous administration, while peak levels occur 30 to 90
minutes after administration. Due to its duration of action of around 5 hours, Humalog is
considered "bolus insulin" as it provides high levels of insulin in a short period of time to
mimic the release of endogenous insulin from the pancreas after meals. Bolus insulin is
often combined with once daily, long-acting "basal insulin" such as ​Insulin Detemir​,
Insulin Degludec​, and ​Insulin glargine to provide low concentrations of background
insulin that can keep blood sugar stable between meals or overnight. Use of basal and
bolus insulin together is intended to mimic the pancreas' production of endogenous
insulin, with a goal of avoiding any periods of hypoglycemia.
 ● Marketed as the brand name product Levemir, insulin detemir has a duration of action of
16-24 hours allowing for once-daily dosing, typically at bedtime. Due to its duration of
action, Levemir is considered "basal insulin" as it provides low concentrations of
background insulin that can keep blood sugar stable between meals or overnight. Basal
insulin is often combined with short-acting "bolus insulin" such as ​Insulin Lispro​, ​Insulin
Glulisine​, and ​Insulin Aspart to provide higher doses of insulin required following meals.
Use of basal and bolus insulin together is intended to mimic the pancreas' production of
endogenous insulin, with a goal of avoiding any periods of hypoglycemia.
● Biosynthetic ​human insulin (insulin human rDNA, INN) for clinical use is manufactured by
recombinant DNA technology Biosynthetic human insulin has increased purity when
compared with extractive animal insulin, enhanced purity reducing antibody formation.
Several analogs of human insulin are available. These insulin analogs are closely
related to the human insulin structure, and were developed for specific aspects of
glycemic control in terms of fast action (prandial insulins) and long action (basal
insulins).​[91] The first biosynthetic insulin analog was developed for clinical use at
mealtime (prandial insulin), ​Humalog (insulin lispro),it is more rapidly absorbed after
subcutaneous injection than regular insulin, with an effect 15 minutes after injection.

3. Characterize the primary counter-regulatory hormone that is increased when hansel

developed hypoglycemia.

● GLUCAGON - 29 amino acid synthesized as proglucagon and proteolytically cleaved to

become glucagon in the alpha cells of the pancreas
● Secretion is done to respond to hypoglycemia because this hormone is the most potent
gluconeogenic hormone
● Also stimulates breakdown of glycogen stores in the liver
● Also stimulates lipolysis for fatty acid beta oxidation and ketone body formation
● NET EFFECT = Increased plasma glucose

BIOCHEMISTRY OF STEROID HORMONES

1. What would be the organs that can possibly be the site of the tumor in this patient?
Describe the biosynthetic pathway of androgen/s in these endocrine organs.

● Ovary - Theca cells which produces both testosterone and androstenedione

● Adrenal Cortex (Zona Reticularis) - Androstenedione
2. How will you go about the diagnostic procedures in order to localize the possible tumor?

● Examination for the levels of testosterone and androstendedione, if both levels are
elevated then probably the tumor is in the adrenals if testosterone only then possible in
the ovary. (DI AKO SURE DITO PLEASE CONFIRM HAHAHA)

FORENSIC BIOCHEMISTRY

1. What is mtDNA

● DNA located in the mitochondria, which represents a very small fraction of the
DNA inside the cell
● It is inherited from the mother and NOT from the father since fathers only transmit
nuclear DNA

2. From whom did the Romanov Family receive their mtDNA

● Mother (Tsarina Alexandra)

3. Where did that person who passed their mtDNA on to the Romanov children get their
mtDNA?

● From the mother of Tsarina Alexandra (grandmother of the children)

4. Does CHAR Nicholas II have the same mtDNA as his children

● Nah bruh, because he received his mtDNA from his own mother (who has a
different mtDNA from the mother of Tsarina Alexandra)

5. In order to test the paternity of Prince Alexei in relation to his father CHAR Nicholas II,
what type of DNA testing is the best?

● Y chromosome analysis - since this is directly passed from father to son, used for
analyzing evidence concerning male contributors
● The presence of Y-chromosome determines “maleness” and is transmitted from
father to son NEVER TO DAUGHTER
● The Y chromosome is inherited vertically as an integral unit without alteration. It
is only the nuclear chromosome that escapes continual reshuffling of genes
during sex cell production / gametogenesis
6. How can the identity of skeletal remain be proven?

● mtDNA testing since this is used for pieces of evidence in small or degraded
quantities (bone, hair, teeth)
● Skeletal remains are compared to samples of maternal relatives

7. Can we use nuclear DNA instead of mtDNA to prove the identity of skeletal remains?

● Old biological samples that lack nuclear material cannot be used for nDNA
analysis such as STR and RFLP

8. Could we use mtDNA to prove Anna Anderson’s true identity? How?

● Compare mtDNA of skeletal remains of the Tsar Alexandra or her children with
Anna Anderson’s own mtDNA