BMS 6050 Biochemistry & Micronutrients Flashcard Deck

Comprehensive flashcard deck covering BMS 6050 Sessions 1 to 4: Vitamins & Iron, Foundations of Biochemistry & Dietary Fuels, Water, Buffers & Acid-Base Physiology, and Lipid Structures.

How do fat-soluble and water-soluble vitamins differ in terms of absorption, storage, and primary clinical risks?

Fat-soluble vitamins (A, D, E, K) require bile salts for absorption, build up large reserves in the liver and body fat, take time to develop deficiency, and carry a higher risk of toxicity. Water-soluble vitamins (B-complex, C) are absorbed directly into the bloodstream, are not stored (except B12), are excreted in urine, and carry a higher risk of rapid deficiency.

Which vitamins are classified as fat-soluble?

Vitamins A, D, E, and K.

Which water-soluble vitamin is stored in the liver for $3\text{--}5\text{ years}$, making its deficiency slow to develop?

Vitamin B12 (cobalamin).

What is the active coenzyme form of thiamine (vitamin B1), and which key energy-producing enzyme requires it?

Thiamine pyrophosphate (TPP), which is required as a coenzyme by pyruvate dehydrogenase (PDH) and $\alpha$-ketoglutarate dehydrogenase.

What reaction converts thiamine to its active coenzyme form, thiamine pyrophosphate (TPP)?

Thiamine reacts with ATP to form thiamine pyrophosphate (TPP) and AMP.

What are the three clinical forms of beriberi caused by thiamine deficiency?

1. Wet beriberi (heart failure, edema)
2. Dry beriberi (neuropathy, muscle wasting)
3. Infantile beriberi (vomiting, lactic acidosis, enlarged heart)

What is the classic clinical triad of acute Wernicke encephalopathy?

Confusion, ataxia, and nystagmus (rapid, uncontrollable eye movements).

What permanent neurological condition develops if Wernicke encephalopathy remains untreated?

Korsakoff syndrome, characterized by confabulation and permanent amnesia.

Why must thiamine be administered BEFORE or together with IV dextrose in an alcoholic patient?

IV dextrose stimulates glycolysis and produces pyruvate. Pyruvate requires thiamine pyrophosphate (TPP) to enter the TCA cycle via pyruvate dehydrogenase (PDH). Giving glucose without thiamine depletes residual TPP, shunting pyruvate to lactate and precipitating or worsening acute Wernicke encephalopathy and lactic acidosis.

What are the two active coenzyme forms of riboflavin (vitamin B2)?

Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).

What are the characteristic clinical signs of riboflavin (vitamin B2) deficiency?

Angular stomatitis (cheilosis), glossitis, dermatitis, and normocytic anemia.

How is flavin adenine dinucleotide (FAD) involved in cellular antioxidant defense?

FAD acts as a coenzyme for glutathione reductase, which uses NADPH to reduce oxidized glutathione (GSSG) back into reduced glutathione (2 GSH), the cell's primary antioxidant.

What are the active coenzyme forms derived from niacin (vitamin B3)?

Nicotinamide adenine dinucleotide ($\text{NAD}^+$) and nicotinamide adenine dinucleotide phosphate ($\text{NADP}^+$).

What disease results from severe niacin deficiency, and what are its classic '4 D's'?

Pellagra, characterized by Diarrhea, Dermatitis (in sun-exposed areas), Dementia, and Death.

What amount of dietary tryptophan is required to synthesize $1\,\text{mg}$ of niacin?

Approximately $60\,\text{mg}$ of dietary tryptophan synthesizes $1\,\text{mg}$ of niacin.

What is the active coenzyme form of pyridoxine (vitamin B6), and what key metabolic reactions does it catalyze?

Pyridoxal phosphate (PLP), which serves as a coenzyme for transamination (AST, ALT), decarboxylation (synthesis of GABA, serotonin, dopamine), and condensation ($\delta$-ALA synthesis for heme production).

Which medication classically causes pyridoxine (vitamin B6) deficiency by binding and inactivating PLP?

Isoniazid (INH), used in tuberculosis treatment.

What clinical manifestations occur when isoniazid inactivates pyridoxal phosphate (PLP)?

Seizures (due to lack of GABA synthesis), sideroblastic anemia (due to impaired heme synthesis via $\delta$-ALA), and peripheral neuropathy.

What active coenzyme form is produced from folic acid (vitamin B9), and what is its role in metabolism?

Tetrahydrofolate (THF), which acts as a one-carbon carrier required for DNA synthesis, specifically purine and thymidylate synthesis.

What form of anemia is caused by folate deficiency, and why does it occur?

Megaloblastic (macrocytic) anemia. Impaired DNA synthesis prevents red blood cell precursors from dividing properly, causing cytoplasm to mature faster than the nucleus.

Why must folic acid be supplemented prior to conception to prevent neural tube defects?

The neural tube closes between days $23\text{--}26$ of gestation, before most women are aware they are pregnant.

Which chemotherapeutic drug competitively inhibits dihydrofolate reductase (DHFR) to block THF regeneration?

Methotrexate.

What two enzymatic reactions require vitamin B12 (cobalamin) as a cofactor?

1. Methionine synthase (converts homocysteine to methionine and regenerates THF)
2. Methylmalonyl-CoA mutase (converts methylmalonyl-CoA to succinyl-CoA)

What symptoms distinguish vitamin B12 deficiency from folate deficiency?

Neurologic symptoms (numbness, tingling, subacute combined degeneration of the spinal cord) and elevated methylmalonic acid (MMA) levels occur ONLY in vitamin B12 deficiency.

Describe the 4-step intestinal absorption pathway of dietary vitamin B12.

1. Stomach: Free B12 binds R-protein (salivary); parietal cells secrete intrinsic factor (IF).
2. Duodenum: Pancreatic enzymes degrade R-protein, allowing B12 to bind IF.
3. Terminal ileum: IF-B12 complex is absorbed by specific mucosal receptors.
4. Blood/Liver: B12 is transported in blood and stored in the liver for $3\text{--}5\text{ years}$.

What is pernicious anemia?

An autoimmune disease causing destruction of gastric parietal cells, leading to a loss of intrinsic factor (IF) and severe vitamin B12 malabsorption.

What laboratory laboratory markers are elevated in BOTH vitamin B12 deficiency and folate deficiency?

Elevated serum homocysteine and macrocytic anemia with hypersegmented neutrophils.

Why is methylmalonic acid (MMA) elevated in B12 deficiency but normal in folate deficiency?

MMA accumulates because methylmalonyl-CoA mutase requires vitamin B12 (deoxyadenosylcobalamin) as an essential cofactor; folate is not involved in this mutase reaction.

Why is it dangerous to treat an undiagnosed macrocytic anemia with folate alone?

Folate bypasses the 'folate trap' and corrects the anemia, masking the underlying B12 deficiency while neurological damage from MMA accumulation continues to progress silently.

What is the biochemical function of vitamin C in collagen synthesis?

Vitamin C acts as a necessary cofactor for prolyl hydroxylase and lysyl hydroxylase, maintaining iron in the reduced $\text{Fe}^{2+}$ state to convert proline and lysine residues into hydroxyproline and hydroxylysine.

What clinical manifestations are seen in scurvy?

Bleeding gums, loose teeth, perifollicular hemorrhage, corkscrew hairs, and poor wound healing due to unstable collagen.

How does vitamin C enhance non-heme iron absorption in the gastrointestinal tract?

Vitamin C reduces insoluble ferric iron ($\text{Fe}^{3+}$) to the soluble ferrous iron ($\text{Fe}^{2+}$) state in the gut lumen.

What are the three active forms of vitamin A and their primary biological roles?

1. Retinol (storage and transport)
2. Retinal (binds opsin to form rhodopsin for vision)
3. Retinoic acid (binds nuclear RAR/RXR receptors for gene regulation, immunity, and cell growth)

How many molecules of retinal are generated from one molecule of dietary $\beta$-carotene?

Two molecules of retinal.

What are the clinical signs of vitamin A deficiency?

Night blindness, xerophthalmia (Bitot spots), dry scaly skin, growth retardation, and impaired immunity.

What are the toxic effects of acute or chronic vitamin A overload?

Teratogenicity (requires pregnancy test before isotretinoin/Accutane use), liver damage, pseudotumor cerebri, nausea, and joint pain.

Detail the 3-organ activation pathway of vitamin D.

1. Skin: UVB converts 7-dehydrocholesterol to vitamin D3 (cholecalciferol).
2. Liver: 25-hydroxylase converts D3 to 25(OH)D (calcidiol, storage form).
3. Kidney: 1$\alpha$-hydroxylase (stimulated by PTH) converts 25(OH)D to 1,25(OH)2D (calcitriol, active hormone).

Contrast Rickets and Osteomalacia.

Rickets occurs in children (unclosed growth plates) leading to bowed legs, rachitic rosary, and soft skull (craniotabes). Osteomalacia occurs in adults (closed growth plates) leading to bone pain, muscle weakness, and demineralization of existing bone.

What is the biochemical defect in renal osteodystrophy?

Chronic kidney failure causes loss of 1$\alpha$-hydroxylase activity, leading to decreased active 1,25(OH)2D, hypocalcemia, secondary hyperparathyroidism, and increased bone breakdown.

What role does vitamin K play in blood coagulation, and how does warfarin antagonize it?

Vitamin K is a cofactor for $\gamma$-glutamyl carboxylase, which carboxylates glutamate residues on clotting factors II, VII, IX, X and proteins C/S, allowing them to bind $\text{Ca}^{2+}$. Warfarin inhibits vitamin K epoxide reductase (VKOR), preventing vitamin K recycling.

Why do all newborn infants routinely receive an intramuscular vitamin K injection at birth?

Newborns have poor placental transfer of vitamin K and a sterile gut lacking K-producing bacteria, putting them at high risk for hemorrhagic disease of the newborn.

What is the primary function of vitamin E ($\alpha$-tocopherol) in cell membranes?

It integrates into phospholipid bilayers and donates hydrogen atoms to lipid peroxyl radicals, acting as a chain-breaking antioxidant to protect membranes from oxidative damage.

Which oxidation state of iron is functionally active in hemoglobin, myoglobin, and cytochromes?

Ferrous iron ($\text{Fe}^{2+}$). The oxidized ferric state ($\text{Fe}^{3+}$) cannot bind $O_2$ and forms methemoglobin.

What are the clinical signs and red blood cell characteristics of iron deficiency anemia?

Small, pale red blood cells (microcytic, hypochromic anemia) accompanied by fatigue, pallor, spoon-shaped nails (koilonychia), glossitis, and ice craving (pica/pagophagia).

What genetic defect causes hereditary hemochromatosis, and how is it treated?

A mutation in the HFE gene leading to chronic iron overload, bronze skin, 'bronze diabetes,' cirrhosis, and cardiomyopathy. It is treated with regular phlebotomy.

Describe the clinical progression and treatment of acute pediatric iron poisoning.

Direct GI lining damage (vomiting, abdominal pain), followed by a deceptive quiet period of apparent improvement, leading to systemic collapse (metabolic acidosis, shock, liver failure). It is treated with deferoxamine (an iron chelator).

What are the four primary classes of biomolecules and their corresponding monomeric building blocks?

1. Carbohydrates (Monosaccharides)
2. Proteins (Amino acids)
3. Nucleic acids (Nucleotides)
4. Lipids (Fatty acids and glycerol)

What chemical bond links monosaccharides into polysaccharides such as starch and glycogen?

Glycosidic bond.

What chemical bond connects amino acids in a protein chain?

Peptide bond.

What type of bond connects nucleotides in DNA and RNA chains?

Phosphodiester bond.

In which cellular compartments do glycolysis, fatty acid synthesis, and the pentose phosphate pathway take place?

The cytoplasm (cytosol).

Which cellular organelle hosts the Citric Acid Cycle (TCA), oxidative phosphorylation, and fatty acid $\beta$-oxidation?

The mitochondrion.

What are the respective roles of the rough and smooth endoplasmic reticulum?

Rough ER: protein synthesis and folding. Smooth ER: lipid synthesis and drug detoxification.

Differentiate exergonic from endergonic reactions in terms of Gibbs free energy ($\Delta G$).

Exergonic reactions have a negative $\Delta G$ (release energy, proceed spontaneously). Endergonic reactions have a positive $\Delta G$ (require energy input).

What is the standard free energy change ($\Delta G$) for ATP hydrolysis to ADP and $P_i$?

$$\Delta G = -30.5\,\text{kJ/mol}$$

Compare the main characteristics of anabolic and catabolic pathways.

Anabolic pathways build complex molecules from small precursors, require energy input (ATP, NADPH), and dominate in the fed state (insulin-driven). Catabolic pathways break down large molecules into simple products, release energy (ATP, NADH, FADH2), and dominate in the fasting state (glucagon-driven).

Which hormone acts as the master regulator of the fed (absorptive) metabolic state?

Insulin.

Which hormone acts as the master regulator of the fasting (post-absorptive) metabolic state?

Glucagon.

What common metabolic intermediate serves as the final convergence point for carbohydrate, fat, and protein breakdown before entering the TCA cycle?

Acetyl-CoA.

What is the body's primary fuel source during the first $24\text{ hours}$ of fasting?

Liver glycogen (via glycogenolysis).

What metabolic shift occurs during days $1\text{--}3$ of fasting when liver glycogen stores are exhausted?

The liver shifts to gluconeogenesis (using amino acids and glycerol), fatty acid oxidation becomes the primary energy source, and muscle protein breakdown increases.

What metabolic adaptation occurs after $3\text{ days}$ of starvation to spare body protein?

The liver produces ketone bodies from fatty acids, allowing the brain to meet ~75% of its energy needs from ketones, thereby reducing the rate of muscle protein catabolism.

What is the energy content per gram for carbohydrates, fats, proteins, and alcohol?

• Carbohydrates: $4\,\text{kcal/g}$ • Protein: $4\,\text{kcal/g}$ • Fat: $9\,\text{kcal/g}$ • Alcohol: $7\,\text{kcal/g}$

Why does dietary fat yield more than double the calories per gram ($9\,\text{kcal/g}$) compared to carbohydrates ($4\,\text{kcal/g}$)?

Fatty acids contain significantly more reduced C–H bonds available for oxidation.

Define Glycemic Index (GI) and contrast high-GI foods with low-GI foods.

Glycemic Index ranks foods based on how rapidly they elevate blood glucose compared to pure glucose (GI = 100). High-GI foods (white bread, white rice) cause a rapid glucose spike and large insulin response. Low-GI foods (legumes, whole grains) cause a gradual glucose rise and sustained energy release.

What are the approximate total caloric reserves stored as fat, muscle protein, and glycogen in a standard $70\,\text{kg}$ adult?

• Fat (adipose tissue): ~100,000–140,000 kcal • Muscle protein: ~25,000 kcal • Glycogen (liver + muscle): ~1,600 kcal total (Liver ~400, Muscle ~1,500)

How do liver glycogen and muscle glycogen differ in their physiological functions?

Liver glycogen maintains systemic blood glucose levels for the body (especially the brain). Muscle glycogen provides glucose exclusively for local muscle contraction during exercise.

List the 9 essential amino acids that must be supplied by the diet.

Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine.

What are conditionally essential amino acids, and give two clinical examples.

Amino acids that are normally non-essential but become essential under specific physiological or pathological conditions. Examples: Tyrosine (requires phenylalanine) and Cysteine (requires methionine).

What enzyme is deficient in Phenylketonuria (PKU), and which amino acid becomes conditionally essential as a result?

Phenylalanine hydroxylase (PAH) is deficient, preventing conversion of phenylalanine to tyrosine; tyrosine becomes essential.

Compare complete and incomplete dietary protein sources.

Complete (high-quality) proteins come from animal sources (meat, fish, eggs, dairy) and contain all 9 essential amino acids. Incomplete (low-quality) proteins come from plant sources and lack adequate amounts of one or more essential amino acids.

What are complementary plant proteins?

Combinations of incomplete plant proteins that together supply all 9 essential amino acids (e.g., combining rice [low in lysine/threonine] with beans [low in methionine]).

What minimum daily intake of carbohydrates is required to achieve a 'protein-sparing' effect?

At least $130\,\text{g/day}$ of carbohydrates.

Define positive and negative nitrogen balance and give clinical examples of each.

Positive nitrogen balance ($\text{N}_{in} > \text{N}_{out}$): net gain in body protein (growth, pregnancy, childhood). Negative nitrogen balance ($\text{N}_{in} < \text{N}_{out}$): net loss of body protein (malnutrition, starvation, severe illness, burn trauma).

What is Kwashiorkor, and what is the biochemical mechanism of its classic sign, pitting edema?

Kwashiorkor is severe protein deficiency despite adequate total calories. Without essential amino acids, the liver cannot synthesize albumin; decreased serum albumin lowers plasma oncotic pressure, causing fluid to leak into interstitial spaces (edema and ascites).

What clinical features distinguish Kwashiorkor from Marasmus?

Kwashiorkor presents with edema, swollen belly, flaky skin, discolored hair, and fatty liver. Marasmus is global caloric starvation presenting with severe tissue wasting ('skin and bones') and NO edema.

Why does a fatty liver develop in Kwashiorkor?

The liver cannot synthesize apolipoproteins needed to assemble VLDL, preventing the export of fat from liver tissue.

Why are omega-3 and omega-6 fatty acids considered essential in human nutrition?

Humans lack the desaturase enzymes required to introduce double bonds beyond carbon 9 from the carboxyl end.

What are the three main components of Total Daily Energy Expenditure (TEE) and their relative percentages?

1. Resting Metabolic Rate (RMR): ~60%
2. Physical Activity: ~30%
3. Thermic Effect of Food (TEF): ~10%

How is Body Mass Index (BMI) calculated, and what are the standard cutoff values for normal weight, overweight, and obesity?

$\text{BMI} = \frac{\text{weight (kg)}}{\text{height}^2 (\text{m}^2)}$ • Normal: $18.5\text{--}25\,\text{kg/m}^2$ • Overweight: $25\text{--}30\,\text{kg/m}^2$ • Obese: $>30\,\text{kg/m}^2$

What are the BMI cutoff ranges for Obese Class I, Obese Class II, and Obese Class III?

• Obese Class I: $30\text{--}35\,\text{kg/m}^2$ • Obese Class II: $35\text{--}40\,\text{kg/m}^2$ • Obese Class III: $>40\,\text{kg/m}^2$

What percentage of total body weight is composed of water, and what are its major biological functions?

Water comprises ~$60\%\text{--}70\%$ of total body weight. It serves as a medium for transport, separates charges, acts as a biological solvent, and dissipates heat.

Describe the dipole structure and geometry of a water molecule.

Water is a polar molecule with V-shaped (bent) geometry. Oxygen is highly electronegative, creating partial negative charges ($\delta^-$) on O and partial positive charges ($\delta^+$) on each H.

How many hydrogen bonds can a single water molecule form, and what is the bond strength of an individual H-bond?

Each water molecule can form up to 4 hydrogen bonds, each with an individual bond strength of ~$20\,\text{kJ/mol}$.

Which physical properties of water contribute directly to thermoregulation?

High heat capacity, high thermal conductivity, and high heat of vaporization (sweat cooling).

How do water molecules orient themselves when forming hydration shells around dissolved ions?

The partial negative oxygen ($\delta^-$) faces dissolved cations ($\text{Na}^+$, $\text{K}^+$), while the partial positive hydrogens ($\delta^+$) face dissolved anions ($\text{Cl}^-$).

Define the term 'amphipathic' molecule.

A molecule containing both hydrophilic (water-loving, polar) and hydrophobic (water-fearing, nonpolar) regions.

What thermodynamic force drives the hydrophobic effect?

The aggregation of nonpolar molecules minimizes their exposed surface area, releasing surrounding water molecules from ordered 'cages' back into the bulk phase, which increases entropy ($\Delta S > 0$).

Differentiate plasma osmolarity from plasma osmolality.

Osmolarity is the number of solute particles per liter of solution ($\text{mOsm/L}$). Osmolality is the number of solute particles per kilogram of solvent ($\text{mOsm/kg}$). Normal plasma osmolality is $285\text{--}295\,\text{mOsm/kg}$.

Identify the dominant cation and anion in Extracellular Fluid (ECF) versus Intracellular Fluid (ICF).

• ECF: Dominant cation = $\text{Na}^+$, dominant anion = $\text{Cl}^-$ • ICF: Dominant cation = $\text{K}^+$, dominant anion = $\text{HPO}_4^{2-}$

How does sodium concentration govern body fluid distribution and clinical hydration states?

Water follows sodium. High ECF $\text{Na}^+$ leads to water retention, edema, and hypertension. Low $\text{Na}^+$ (hyponatremia) causes cellular swelling, resulting in confusion and seizures.

Which hormone is released by the posterior pituitary in response to increased plasma osmolality?

Vasopressin, also known as antidiuretic hormone (ADH), which stimulates renal water reabsorption.

What is the ion product constant of water ($K_w$) at $25^\circ\text{C}$, and what is the formula for pH?

$K_w = [\text{H}^+][\text{OH}^-] = 1 \times 10^{-14}$$\text{pH} = -\log[\text{H}^+]$

What is normal arterial blood pH, and what is the pH range compatible with human life?

Normal blood pH = $7.35\text{--}7.45$. Life-compatible range = $6.8\text{--}7.8$.

Define a Brønsted-Lowry weak acid versus a strong acid.

A strong acid dissociates completely in water and cannot act as a buffer (e.g., HCl). A weak acid dissociates partially, establishing an equilibrium between the acid (HA) and its conjugate base ($\text{A}^-$).

Define $p K_a$ and explain its relationship to acid strength.

$p K_a = -\log K_a$. It represents the pH at which an acid is 50% dissociated ($[\text{HA}] = [\text{A}^-]$). A lower $p K_a$ indicates a stronger acid.

Over what pH range does a weak acid buffer solution function most effectively?

Within $1\,\text{pH unit}$ above or below its $p K_a$ ($p K_a \pm 1$).

What is the most abundant metabolic acid produced daily by the human body?

Carbon dioxide ($\text{CO}_2$), producing ~$15,000\text{--}20,000\,\text{mmol/day}$ of volatile acid via the carbonic anhydrase reaction.

List four major non-volatile (fixed) metabolic acids that must be excreted by the kidneys.

1. Lactic acid
2. Ketone bodies (acetoacetic acid, $\beta$-hydroxybutyric acid)
3. Gastric hydrochloric acid (HCl)
4. Uric acid

Write the general Henderson-Hasselbalch equation.

$$\text{pH} = p K_a + \log\left(\frac{[\text{A}^-]}{[\text{HA}]}\right)$$