Biochemistry - nutrition

• A, D, E, K
• Absorption dependent on gut (ileum) and pancreas
• Toxicity is more common due to accumulation in fat
• **Malabsorption syndromes (steatorrhea), such as cystic fibrosis and sprue, or mineral oil intake causes fat-soluble vitamin deficiencies

• B₁: thiamine (TPP)
• B₂: riboflavin (FAD, FMN)
• B₃: niacin (NAD+)
• B₅: pantothemic acid (CoA)
• B₆: pyridoxine (PLP)
• B₇: biotin
• B₉: folate
• B₁₂: cobalamin
• C: ascorbic acid
• **all wash out easily from the body except B₁₂ and folate (stored in liver)
• B-complex deficiencies often result in dermatitis, glossitis, and diarrhea

• Function:
• -Antioxidant
• -Constituient of visual pigments (retinal)
• -Essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells)
• -Prevents squamous metaplasia
• -Used to treat measles and AML, subtype M3

*Retinol is vitamin A, so think retin-A (used topically for wrinkles and acne)

Source: liver and leafy vegetables

• Deficiency:
• -Night blindness
• -Dry skin

• Excess:
• -Arthralgias
• -Fatigue
• -Headaches
• -Skin changes
• -Sore throat
• -Alopecia
• -Teratogenic (cleft palate, cardiac abnormalities)
• *negative pregnancy test + birth control pills are needed before isotretinoin is prescribed for severe acne

• Function:
• -Thiamine is used in thiamine pyrophosphate (TPP) which is a cofactor for several enzymes in decarboxylation reactions:
• ↦ Pyruvate dehydrogenase (links glycolysis to TCA cycle)
• ↦ α-ketoglutarate dehydrogenase (TCA cycle)
• ↦ Transketolase (HMP shunt)
• ↦ Branched-chain amino acid dehydrogenase
• **α-ketoglutarate DH, Transketolase, and Pyruvate DH are required for ATP synthesis

• Deficiency:
• -Impaired glucose breakdown → ATP depletion worsened by glucose infusion
• -High aerobic tissues (brain and heart) are affected first
• -Wernicke-Korsakoff syndrome and beriberi
• -Seen in malnutrition as well as alcoholism (2° to malnutrition and malabsorption)

• B1 deficiency
• Confusion
• Opthalmoplegia
• Ataxia
• Confabulation
• personality change
• memory loss (permanent)
• *Damage to medial dorsal nucleus of thalamus, mammillary bodies

*Ber1Ber1 to remember vitamin B1

• Dry beriberi:
• - polyneuritis
• - symmetrical muscle wasting

• Wet beriberi:
• -high-output cardiac failure (dilated cardiomyopathy)
• -edema

• Function:
• -Cofactor in oxidation and reduction (e.g., FADH₂)
• FAD and FMN are derived from riboFlavin (B₂ = 2 ATP)

• Deficiency:
• -Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)
• -Corneal vascularization
• **The 2 C's of B₂

• Function:
• -Constituent of NAD+, NADP+ (used in redox reactions)
• -Derived from tryptophan
• -Synthesis requires vitamin B6
• *NAD derived from Niacin (B₃ = 3 ATP)

• Deficiency:
• -Glossitis
• -Severe deficiency leads to pellegra, which can be caused by Hartnup disease (↓ tryptophan absorption), malignant carcinoid syndrome (↑ tryptophan metabolism, and INH (↓ vitamin B6)

• Sx of pellegra:
• -Diarrhea
• -Dementia
• -Dermatitis
• *3D's of B₃

• Excess: 
• -Facial flushing (due to pharmacologic doses for treatment of hyperlipidemia

B₅ is "pento"thenate

• Function:
• -Essential component of CoA (a cofactor for acyl transfer) and fatty acid synthase

• Deficiency:
• -Dermatitis
• -Enteritis
• -Alopecia
• -Adrenal insufficiency

• FUnction:
• -Converted to pyridoxal phosphate, a cofactor used in transamination, decarboxylation reactions, glycogen phosphorylase
• -Synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepinephrine and GABA

• Deficiency:
• -Convulsions
• -Hyperirritability
• -Peripheral neuropathy (deficiency inducible by INH and oral contraceptives)
• -sideroblastic anemias due to impaired hemoglobin synthesis and iron excess

• Function:
• -Cofactor for carboxylation enzymes (which add a 1-carbon group):
• ☉ Pyruvate carboxylase: pyruvate (3C) → oxaloacetate (4C)
• ☉ Acetyl-CoA carboxylase: acetyl-CoA (2C) → malonyl-CoA (3C)
• ☉ Propionyl-CoA carboxylase: propionyl-CoA (3C) → methylmalonyl-CoA (4C)

• Deficiency: relatively rare
• -Dermatitis
• -Alopecia
• -enteritis
• -Cuased by antibiotic use or excessive ingestion of raw egg

**"Avidin in egg whites avidly binds biotin"

• Source:
• -Found in leafy green vegetables
• *Folate from Foliage
• -Small reserve pool stored primarily in the liver

• Function:
• -Converted to tetrahydrofolate (THF); a coenzyme for 1-carbon transfer/methylation reactions
• -Important for the synthesis of nitrogenous bases in DNA and RNA

• Deficiency:
• -Macrocytic, megaloblastic anemia
• -No neurologic symptoms (as opposed to vitamin B12 deficiency)
• -Most common vitamin deficiency in the US
• -Seen in alcoholism and pregnancy
• -Deficiency can be caused by several drugs (e.g., phenytoin, sulfonamides, MTX)
• -Supplemental folic acid in early pregnancy reduces neural tube defects

• Source:
• -Found in animal products
• -Synthesized only by microorganisms
• -Very large reserve pool (several years) stored primarily in the liver

• Function:
• -Cofactor for homocysteine methyltransferase (transfers CH3 group as methylcobalamin) and methylmalonyl-CoA mutase

• Deficiency:
• Causes: usually by malabsorption (sprue, enteretis, Diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn's disease)
• -Macrocytic, megaloblastic anemia
• -hypersegmented PMNs
• -Neurologic symptoms  (paresthesias, subacute combined degeneration) due to abnormal myelin
• -Prolonged deficiency leads to irreversible nervous system damage

• Dx:
• -Schilling test to detect the etiology of the deficiency

• B12 deficiency:
• -macrocytic, megaloblastic anemia
• -

• ATP + methionine → SAM
• SAM transfers methyl units
• Regeneration of methionine (and thus SAM) is dependent on vitamin B₁₂ and folate
• **SAM the methyl donor man
• Required for the conversion of NE to epinephrine

• Source: 
• -Found in fruits and vegetables

• Function:
• -Antioxidant
• -Also facilitates iron absorption by keeping iron in Fe2+ reduced state **Pronounce "absorbic" acid
• -Necessary for hydroxylation of proline and lysine in collagen synthesis
• -Necessary for dopamine β-hydroxylase, which converts dopamine to NE

• Deficiency: Scruvy:
• -Swollen gums
• -Bruising
• -Hemarthrosis
• -Anemia
• -Poor wound healing
• -Weakened immune response
• **Vitamin C deficiency causes sCurvy due to a Collagen synthesis defect

• Excess:
• -Nausea, vomiting, diarrhea
• -fatigue, sleep problems
• -Can increase risk of iron toxicity in predisposed individuals (transfusions, hereditary hemochromatosis)

• D₂ = ergocalciferol: ingested from plants
• D₃ = cholecalciferol: consumed in milk, formed in sun-exposed skin
• 25-OH D₃ = storage form
• 1,25-(OH)₂ D₃ (calcitriol) = active form

• Function:
• - ↑ intestinal absorption of calcium and phosphate

- ↑ bone mineralization

• Deficiency:
• -Rickets in children: bone pain and deformities)
• 
• -Osteomalacia in adults (bone pain and muscle weakness)
• -hypocalcemic tetany
• -Breast milk has ↓ vitamin D (supplement in dark-skinned patients)

• Excess:
• -hypercalcemia
• -hypercalciuria
• -loss of appetite
• -stupor
• -Seen in sarcoidosis (↑ activation of vitamin D by epithelioid macrophages)

• Function:
• -Antioxidant (protects erythrocytes and membranes from free-radical damage)
• **E is for Erythrocytes

• Deficiency:
• -↑ fragility of erythrocytes (hemolytic anemia)
• -Muscle weakness
• -Posterior column and spinocerebellar tract demyelination

• Function:
• -Catalyzes γ-carboxylation of glutamic acid residues on various proteins concerned with blood clotting
• -Synthesized by intestinal flora
• **K is for Koagulation
• -Needed for synthesis of clotting factors II, VII, IX, X, and proteins C and S
• -Warfarin: Vitamin K antagonist

• Deficiency:
• -Neonatal hemorrhage with ↑ PT and ↑ aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize vitamin K
• -Can also occur after prolonged use of broad-spectrum antibiotics
• -Not in breast milk; neonates are given vitamin K injection at birth to prevent hemorrhage

• Function:
• -Essential for activity of 100+ enzymes
• -important in the formation of zinc fingers (transcription factor motif)

• Deficiency:
• -Delayed wound healing
• -hypogonadism
• -↓ adult hair (axillary, facial, pubic)
• -dysgeusia
• -anosmia
• -May predispose to alcoholic cirrhosis

• NAD+ is the limiting reagent
• Alcohol dehydrogenase operates via zero-order kinetics

Inhibits alcohol dehydrogenase and is an antidoe for methanol or ethylene glycol posoning

Inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates, contributing to hangover symptoms)

• Ethanol metabolism increases NADH/NAD+ ratio in the liver, causing diversion of pyruvate to lactate and OAA to malate
• -Inhibits gluconeogenesis and stimulates fatty acid synthesis
• → hypoglycemia and hepatic fatty change (hepatocellular steatosis) seen in chronic alcoholics
• Overproduction of lactate → acidosis
• Depletion of oxaloacetate shuts down the TCA cycle, sthunting acetyl-CoA into ketone production
• Breakdown of excess malate ↑ NADPH and thus fatty acid synthesis

• Protein malnutrition
• Presentation:
• -skin lesions
• -edema
• -liver malfunction (fatty change due to decreased apolipoprotein synthesis)
• -Small child with swollen belly

• **MEAL:
• Malnutrition
• Edema
• Anemia
• Liver (fatty)

• Energy malnutrition
• Presentation:
• -tissue and muscle wasting
• -loss of subcutaneous fat
• -variable edema

**Marasmus results in Muscle wasting