Key Micronutrients

Why This Matters

Micronutrients are the biochemical workhorses behind nearly every metabolic pathway you'll encounter in Advanced Nutrition. While macronutrients provide the fuel, vitamins and minerals act as coenzymes, cofactors, and structural components that determine whether those metabolic reactions actually happen. You're being tested on your ability to connect specific micronutrients to their mechanisms of action—understanding why a B-vitamin deficiency disrupts energy metabolism or how mineral interactions affect absorption is exactly what separates surface-level memorization from true nutritional competence.

The key to mastering this material is recognizing patterns: which micronutrients function as antioxidants, which serve as enzyme cofactors, and which play structural roles. Exam questions often ask you to predict deficiency symptoms based on biochemical function or to explain nutrient-nutrient interactions. Don't just memorize that Vitamin C supports collagen synthesis—know why (it's a cofactor for hydroxylation reactions) and what happens when it's missing. That mechanistic thinking is what earns full credit on FRQs.

---

Fat-Soluble Vitamins: Storage and Toxicity Considerations

Fat-soluble vitamins (A, D, E, K) are absorbed with dietary lipids and stored in adipose tissue and the liver. This storage capacity means deficiencies develop slowly, but toxicity is a real concern with excessive supplementation.

Vitamin A

• Two dietary forms with different bioavailability—preformed retinoids from animal sources are readily absorbed, while provitamin carotenoids from plants require enzymatic conversion
• Essential for the visual cycle—retinal is a component of rhodopsin, the photoreceptor pigment critical for low-light vision
• Regulates gene expression for cell differentiation, making it crucial for epithelial integrity and immune function

Vitamin D

• Functions as a hormone rather than a traditional vitamin—after hydroxylation in the liver and kidneys, calcitriol ($1,25(OH)_2D$) regulates calcium homeostasis
• Synthesized endogenously through UVB exposure converting 7-dehydrocholesterol in the skin, making it unique among vitamins
• Deficiency impairs bone mineralization—causes rickets in children (growth plate abnormalities) and osteomalacia in adults (soft bones)

Vitamin E

• Primary lipid-soluble antioxidant—alpha-tocopherol protects polyunsaturated fatty acids in cell membranes from peroxidation
• Works synergistically with Vitamin C—after neutralizing free radicals, oxidized Vitamin E is regenerated by ascorbic acid
• Deficiency is rare but causes neurological dysfunction due to oxidative damage to nerve cell membranes

Vitamin K

• Essential cofactor for carboxylation reactions—activates clotting factors II, VII, IX, and X by adding carboxyl groups to glutamate residues
• Two bioactive forms: K1 (phylloquinone) from leafy greens and K2 (menaquinone) from bacterial synthesis and fermented foods
• Supports bone health through osteocalcin activation, linking it to calcium metabolism beyond its clotting role

---

Water-Soluble Antioxidants and Collagen Synthesis

Unlike fat-soluble vitamins, water-soluble vitamins are not stored significantly and require regular dietary intake. Excess amounts are typically excreted in urine, making toxicity rare but deficiency more common.

Vitamin C (Ascorbic Acid)

• Cofactor for hydroxylase enzymes—essential for proline and lysine hydroxylation in collagen synthesis, explaining why scurvy causes connective tissue breakdown
• Regenerates other antioxidants—reduces oxidized Vitamin E and maintains iron in its ferrous ($Fe^{2+}$) state for enzyme function
• Enhances non-heme iron absorption in the gut by reducing ferric ($Fe^{3+}$) to ferrous iron, a key nutrient-nutrient interaction

---

B-Vitamins: Energy Metabolism and Coenzyme Function

B-vitamins function primarily as coenzymes or coenzyme precursors in metabolic pathways. Understanding which B-vitamin is associated with which coenzyme is essential for predicting deficiency effects.

Thiamin (B1)

• Forms thiamin pyrophosphate (TPP)—a coenzyme for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase in carbohydrate metabolism
• Critical for ATP production—deficiency causes beriberi (wet = cardiovascular; dry = neurological) due to impaired energy metabolism in high-demand tissues
• Wernicke-Korsakoff syndrome results from severe deficiency, commonly seen in chronic alcoholism due to impaired absorption

Riboflavin (B2)

• Precursor to FAD and FMN—flavin coenzymes essential for oxidation-reduction reactions in the electron transport chain
• Involved in metabolism of other vitamins—required for converting B6 to its active form and activating folate
• Deficiency signs include angular cheilitis and glossitis, reflecting its role in maintaining mucosal integrity

Niacin (B3)

• Forms NAD+ and NADP+—central electron carriers in glycolysis, TCA cycle, and fatty acid synthesis
• Can be synthesized from tryptophan—60 mg tryptophan yields approximately 1 mg niacin, creating a protein-niacin connection
• Pellagra (the 4 D's): dermatitis, diarrhea, dementia, and death—a classic deficiency presentation to know for exams

Vitamin B6 (Pyridoxine)

• Forms pyridoxal phosphate (PLP)—coenzyme for over 100 reactions, primarily in amino acid metabolism including transamination
• Essential for neurotransmitter synthesis—required for producing serotonin, dopamine, and GABA from amino acid precursors
• Deficiency causes microcytic anemia because PLP is needed for heme synthesis (specifically ALA synthase)

Folate (B9)

• Carries one-carbon units—tetrahydrofolate (THF) is essential for nucleotide synthesis and methylation reactions
• Critical during pregnancy—adequate intake prevents neural tube defects; this is why fortification of grains is mandated
• Works with B12 in the methionine cycle—the "methyl-folate trap" explains why B12 deficiency causes functional folate deficiency

Vitamin B12 (Cobalamin)

• Only vitamin containing a metal ion (cobalt)—required for two enzymatic reactions: methionine synthase and methylmalonyl-CoA mutase
• Requires intrinsic factor for absorption—pernicious anemia results from autoimmune destruction of gastric parietal cells
• Deficiency causes megaloblastic anemia and neurological damage—the neurological effects distinguish B12 deficiency from folate deficiency

---

Minerals for Oxygen Transport and Energy

These minerals are directly involved in oxygen delivery and cellular respiration. Their metabolism is tightly regulated because both deficiency and excess can be harmful.

Iron

• Central component of heme proteins—hemoglobin (oxygen transport), myoglobin (muscle oxygen storage), and cytochromes (electron transport)
• Two dietary forms with different absorption: heme iron (animal sources, ~25% absorbed) vs. non-heme iron (plant sources, ~5% absorbed)
• Absorption is tightly regulated at the enterocyte level because humans have no physiological mechanism for iron excretion

Copper

• Essential for iron metabolism—ceruloplasmin oxidizes $Fe^{2+}$ to $Fe^{3+}$ for transferrin binding, explaining why copper deficiency mimics iron deficiency
• Cofactor for antioxidant enzymes—superoxide dismutase (SOD) requires copper for neutralizing reactive oxygen species
• Required for collagen cross-linking—lysyl oxidase needs copper, connecting it to connective tissue integrity

---

Minerals for Bone and Structural Integrity

These minerals provide structural support and are involved in maintaining the skeletal system. Calcium metabolism is particularly complex, involving hormonal regulation and multiple organ systems.

Calcium

• 99% stored in bone as hydroxyapatite crystite—bone serves as both structural support and a calcium reservoir
• Tightly regulated serum levels—parathyroid hormone, calcitonin, and Vitamin D maintain calcium within a narrow range (8.5-10.5 mg/dL)
• Beyond bone: essential for muscle contraction, neurotransmitter release, and blood clotting cascade activation

Magnesium

• Cofactor for over 300 enzymes—particularly those involving ATP (Mg-ATP is the actual substrate for kinases)
• Regulates calcium channels—acts as a natural calcium blocker, explaining its role in muscle relaxation and blood pressure regulation
• Deficiency is underdiagnosed because serum levels don't reflect intracellular or bone stores accurately

---

Minerals for Immune Function and Enzyme Activity

These trace minerals serve as cofactors for enzymes critical to immune response, antioxidant defense, and metabolic regulation.

Zinc

• Cofactor for over 300 enzymes—including carbonic anhydrase, alcohol dehydrogenase, and DNA/RNA polymerases
• Essential for immune cell development—deficiency impairs T-cell function and increases susceptibility to infections
• Competes with copper for absorption—excessive zinc supplementation can induce copper deficiency, a classic nutrient interaction

Selenium

• Incorporated into selenoproteins—glutathione peroxidase (antioxidant) and iodothyronine deiodinases (thyroid hormone activation)
• Works synergistically with Vitamin E—both protect against oxidative damage through different mechanisms
• Narrow therapeutic window—deficiency causes Keshan disease (cardiomyopathy), but excess causes selenosis

---

Minerals for Thyroid and Metabolic Regulation

These minerals directly influence metabolic rate through their roles in thyroid hormone synthesis and function.

Iodine

• Essential component of thyroid hormones—T3 (triiodothyronine) and T4 (thyroxine) contain 3 and 4 iodine atoms respectively
• Deficiency causes goiter—the thyroid enlarges in an attempt to capture more iodine from circulation
• Most significant cause of preventable intellectual disability worldwide—maternal deficiency during pregnancy causes cretinism

---

Electrolytes: Fluid Balance and Nerve Function

Electrolytes maintain osmotic balance and are essential for generating electrical impulses in nerve and muscle cells. The sodium-potassium ratio in the diet is often more important than absolute amounts.

Potassium

• Primary intracellular cation—maintains cell membrane potential through the $Na^+/K^+$-ATPase pump
• Counteracts sodium's effect on blood pressure—high potassium intake promotes sodium excretion and vasodilation
• Deficiency (hypokalemia) causes muscle weakness and cardiac arrhythmias due to disrupted electrical signaling

Sodium

• Primary extracellular cation—essential for maintaining blood volume and osmotic pressure
• Excess intake linked to hypertension—increases blood volume and vascular resistance in salt-sensitive individuals
• Deficiency is rare in typical diets but can occur with excessive sweating, vomiting, or diuretic use

---

Quick Reference Table

---

Self-Check Questions

1. Which two B-vitamins are involved in one-carbon metabolism, and what clinical condition results when their interaction is disrupted by B12 deficiency?

2. Compare the mechanisms by which Vitamin C and Vitamin E function as antioxidants. In which cellular compartments does each primarily operate?

3. A patient presents with anemia that doesn't respond to iron supplementation. Which other mineral deficiency should you consider, and why?

4. Explain why folate supplementation alone is dangerous when B12 deficiency is suspected. What symptoms would be masked versus what would progress?

5. Compare the roles of calcium and magnesium in muscle function. How does their competition for absorption affect dietary recommendations?