BIOCHEM 4.1 - OTHER KEY NUTRIENTS OF METABOLISM

Key Molecules of Metabolism

• The lecture discusses water, electrolytes, micronutrients, mineral metabolism, vitamins, and electron carriers

Objectives

• Understand water and electrolytes roles in digestion and absorption, and their connection with micronutrients and water movement
• Evaluate water movements during changes in pressure and ion concentrations
• Briefly explain iron and copper metabolism within erythrocytes and hepatocytes
• Compare vitamin solubility and storage, and specify which vitamins are stored in the liver
• Briefly explain the significance and metabolism of vitamins A, B9, and B12, specifically relating to development
• Compare and contrast vitamin deficiencies, focusing on pregnancy and infancy
• Connect vitamins to their corresponding deficiencies and symptoms
• Contrast the consequences of vitamin deficiency for newborns versus adults
• Assess vitamin interactions in terms of promoting effects and masking deficiencies
• Briefly explain electron carriers, their generation, and the necessary vitamins

Case Study 1: 15-Year-Old Male

• A 15-year-old male presents with fatigue, breathlessness, and leg pain on walking
• Parents noticed paleness and yellowing of the eyes over the past two years
• The patient had a recent upper respiratory infection
• Lab results show severe macrocytic anemia (hemoglobin 5.1 g/dL), leukopenia, thrombocytopenia, and icterus, which are all secondary to hemolysis and splenomegaly
• The findings mimic acute leukemia or pseudothrombotic microangiopathy with mild hematological findings, including reversible megaloblastic anemia
• The patient is a vegetarian who rarely consumes meat, fruits, or vegetables
• Severe B12 deficiencies are a concern in children ages 2-12 due to a risk of neurodevelopmental delay and regression
• Infants with B12 deficiency may have vomiting, lethargy, failure to thrive, hypotonia, and developmental regression
• Around 50% of infants with B12 deficiency exhibit abnormal movements like tremors or twitches due to the fact B12 is vital for brain development

Case Study 2: 45-Year-Old Woman

• A 45-year-old vegetarian woman presents with tiredness and paleness
• She experiences heavy and prolonged menstruation
• Her hematocrit is 0.32 (reference range 0.36-0.46) and hemoglobin is 90 g/L (reference range 120-160 g/dL)
• This indicates iron deficiency anemia
• Daily iron needs are approximately 1mg for males, 2mg for menstruating females, and about 3mg during pregnancy
• Iron maintains hemoglobin, cytochromes, and iron-sulfur complexes for oxygen transport

Water and Electrolytes

• The body retains most of the water (average 10L) via reabsorption in the small intestine, and the colon reabsorbs 90% of water that enters it; ~150-250 ml is excreted in stool
• Electrolytes are secreted in the salivary glands, stomach, and pancreas
• Sodium-Potassium ATPase helps absorption into enterocytes by transporting sodium out of the cell to increase negative potential, which then hyperpolarizes the membrane and drives passive transport

Micronutrients

• Vitamins and trace elements act as micronutrients
• Micronutrients form prosthetic groups and serve as cofactors
• Major minerals include sodium, potassium, chloride, calcium, phosphate, and magnesium
• Dietary requirements vary from micrograms to grams depending on the mineral
• Minerals maintain the osmolarity of extracellular fluid and transmembrane potential/membrane electrical potential
• They also have crucial roles in metabolism

Water and Sodium Metabolism

• Water and sodium are regulated to maintain fluid balance and blood pressure

Iron Metabolism

• Iron is vital for oxygen transfer and is a component of heme
• The human body carries around 3 to 4 grams of iron
• Approximately 75% of iron resides in hemoglobin
• Approximately 25% of iron resides in the tissues
• Iron is carried bound to transferrin and stored as ferritin and hemosiderin
• Ferric form (Fe3+) occurs in dietary iron
• Iron needs increase during growth or pregnancy
• Iron deficiency causes anemia and defective erythropoiesis

Copper Metabolism

• Copper neutralizes reactive oxygen species like superoxide
• It is associated with oxygenase enzymes, such as superoxide dismutase
• Copper is essential for collagen cross-linking
• Absorbed copper binds to albumin in plasma and is then taken up by hepatocytes
• Copper deficiencies can cause anemia
• Copper excess can cause liver cirrhosis

Vitamin Solubility

• Fat-soluble vitamins are associated with body fat, stored in tissues, and circulating concentrations remain consistent
• Fat-soluble vitamins are not easily absorbed from the diet
• Vitamins A, D, E, and K are fat-soluble
• Vitamins A and D behave like hormones and have the potential to be harmful at high concentrations
• Fat malabsorption can cause a deficiency of fat soluble vitamines
• Water-soluble vitamins have no storage capacity, with the exception of B12
• Water-soluble vitamins must be supplied by diet, with excess excreted in urine
• Vitamins B and C are water-soluble.
• B-complex vitamins are cofactors for carbohydrate, lipid, and protein metabolism
• A higher caloric intake = a higher need for B-complex vitamins
• Vitamin C acts as a reducing agent
• Vitamin deficiencies are specific and related to lack of dietary intake

Vitamin A Metabolism

• Vitamin A, also known as retinol, retinal, and retinoic acid, has active forms of retinal and retinoic acid
• Provitamin A is a plant pigment called carotenoids
• Dietary forms of vitamin A convert to retinol, then to active retinal and retinoic acid
• Vitamin A is stored in the liver as retinyl esters (retinol palmitate) bound to cytosolic retinol-binding proteins (CRBP)
• Lecithin-retinol acyltransferase converts retinol into retinyl esters for storage
• From the liver, the vitamin A compound binds to retinol-binding protein (RBP) for cell interactions via a membrane receptor
• Retinoic acid acts as a signaling molecule and has roles in cellular growth, differentiation, proliferation, maintenance of epithelia, embryonic development, and organogenesis
• A high vitamin A intake can lead to congenital birth anomalies and is not recommended during pregnancy

Vitamin B

• Consists of multiple variants: B1, B2, B3, B5, B6, B7, B9, and B12
• Vitamin B is necessary for normal metabolism and acts as a cofactor for carbohydrates, proteins, and fat metabolism
• A higher carb intake translates to greater need for thiamine and other B vitamins
• Niacin is related to energy needs, while greater folate is needed during replication and purine and pyrimidine synthesis

B9 Folate (Folic Acid)

• Folate has many derivatives
• It is involved in single-carbon transfer reactions for methylation
• Folate is necessary for choline, serine, glycine, and methionine synthesis
• It is also necessary for purine and pyrimidine synthesis
• Folate is essential during pregnancy as a preventative against open neural tube defects due to its vital role in differentiation and mobilization of neural crest cells

B12 Cobalamin

• Cobalamin contains cobalt and forms part of the heme structure
• B12 is responsible for nucleic acid synthesis, erythrocyte production, and folate recycling
• Cobalamin controls homocysteine metabolism and acts as a cofactor for methionine synthase

Vitamins as Precursors of Electron Carriers

• Vitamins play a crucial role in the formation of electron carriers like NAD+, NADP+, FAD, and FMN
• Nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+) participate in oxidoreductase reactions, requiring Synthesis from B3 (niacin)
• Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) are water-soluble carriers that contain riboflavin and act as cofactors of oxidoreductases tightly bound to enzymes for redox reactions