USMLE - Nutrition

All but B12 and folate which are stored in liver

Dermatitis, Glossitis, Diarrhea

Antioxidant
Constituent 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, AML (subtype M3), wrinkles and acne
Found in liver and leafy vegetables

Night blindness and dry skin
Arthritis, Fatigue, Headache, Skin changes, Sore Throat, Alopecia, Teratogenic (cleft palate, cardiac abnormalities)

Thiamine
Part of Thiamine PyroPhosphate (TPP), a cofactor for decarboxylation reactions: “ATP Branch”
Pyruvate dehydrogenase (Glycolysis, TCA cycle), α-ketoglutarate dehydrogenase (TCA cycle), Transketolase (HMP shunt), Branched-chain AA dehydrogenase

Impaired glucose breakdown –> ATP Depletion worsened by glucose infusion
Highly aerobic tissue (brain and heart) affected first
Malnutrition or Alcoholism
Wernicke-Korsakoff, Beriberi

VitB1
Confusion, Ophthalmoplegia, Ataxia + Confabulation, Personality changes, Memory loss
Damage to medial dorsal nucleus of Thalamus, Mammillary bodies

VitB1
Polyneuritis, Symmetrical muscle wasting

VitB1
High output cardiac failure (Dilated Cardiacmyopathy), Edema

Riboflavin
Cofactor in oxidation and reduction (FADH2). FAD and FMN are derived from B2 and yield 2 ATPs
“2 Cs of B2”
Cheilosis and Corneal vascularization

Niacin
Constituent of NAD+ and NADP+ used in RedOx reactions to produce 3 ATP (B3 –> 3 ATP)
Derived from Tryptophan
Synthesis requires VitB6 and VitB2
Glossitis, Pellagra
Facial flushing due to pharmacologic doses for treatment of hyperlipidemia

Hartnup Disease (↓ Tryptophan absorption), Malignant Carcinoid Syndrome (↑ Tryptophan metabolism), INH (↓ VitB6), VitB3 deficiency

Diarrhea, Dermatitis, Dementia

Pantothenate “PENTOthenate”
Essential component for CoA and Fatty Acid Synthase
Dermatitis, Enteritis, Alopecia, Adrenal insufficiency

Pyridoxine
Converted into Pyridoxal Phosphate
Cofactor for Transamination, Decarboxylation, Glycogen phosphorylase
Synthesizes Crystathionine, Heme, Niacin, Histamine, Neurotransmitters (5HT, Epi, NE, GABA)
Convulsions, Hyperirritability, Peripheral neuropathy, Sideroblastic Anemia (impaired hemoglobin synthesis and iron excess)
INH or oral contraceptives can lead to it?

Biotin
Cofactor for Carboxylation enzymes that add 1 carbon group
Pyruvate carboxylase, Acetyl-CoA carboxylase, Propionyl-CoA carboxylase
Rare, Dermatitis, alopecia, enteritis
Caused by antibiotics or ingestion of raw eggs

Folic Acid

THF

Coenzyme for 1 carbon transfer/methylation

Nitrogenous bases in DNA and RNA

Leafy vegetables

Small reserve pool stored in liver

Macrocytic, Megaloblastic anemia, No neurological symptoms (as opposed to B12)
Most common deficiency in US
Alcoholism, Pregnancy, Phenytoin, Sulfonamides, MTX
Given to prevent neural tube defects in early pregnancy

Cobalamin
Cofactor for homocysteine methyltransferase (transfers CH3 groups as methylcobalamin and methylmalonyl-CoA mutase)
Found in animal products
Synthesized by microorganisms
Very large reserve pool (several years) stored in liver

Macrocytic Megaloblastic anemia, Hypersegmented PMNs, Neurological symptoms (paresthesia) due to abnormal myelin. Prolonged deficiency leads to irreversible nervous system damage
Malabsorption (sprue, enteritis, Diphyllobothrium latum), Lack of IF (pernicious anemia, gastric bypass surgery), Absence of terminal ileum (Crohn’s disease)
Schilling test to detect etiology of the deficiency

Homocysteine + THF-CH3 –> [Homocysteine MethylTransferase w/ B12] –> Methionine + THF
Methionine gives CH3 for anabolic reactions
THF ->->-> dTMP pyrimidines
Odd # fatty acids –> Methylmalonyl-CoA –> [B12] –> Succinyl-CoA

Homocysteine ->->-> [B6] –> Cysteine Succinyl-CoA –> [B6] –> Hb

Odd # fatty acids –> Methylmalonyl-CoA –> [B12] –> Succinyl-CoA –> [B6] –> Hb

ATP + Methionine

Transferes methyl units

Methionine + ATP --> SAM --> CH3 (for anabolic pathways) + Homocysteine

Regeneration requires B12 and Folate

Required for conversation of NE to Epi

Ascorbic Acid
Antioxidant, Facilitate iron absorption by keeping iron in reduced Fe2+ state
Necessary for hydroxylation of proline and lysine in collagen
Necessary for Dopamine-β-Hydroxylase to convert DA into NE
Found it fruits and Vegetables

Weakened immune response, Scurvy due to collagen synthesis defect (swollen gums, bruising, hemarthrosis, anemia, poor wound healing)
Nausea, Vomiting, Diarrhea, Fatigue, Sleep Problems, and Risk of Iron Toxicity in predisposed individuals (transfusions, hemochromatosis)

D2 - Ergocalciferol - ingested from plants
D3 - Cholecalciferol - consumed in milk, sun exposure
25OH D3 is storage form
1,25, OH2 D3 is active form

Intestinal absorption of Ca and PO4, Increased bone mineralization
Rickets in children, Osteomalacia in adults,
HypoCa tetany. Decreased VitD in dark skinned pts.
HyperCa, Hypercalcinuria, loss of appetite, stupor. Seen in Sarcoidosis

"E is for Erythrocytes"
Antioxidant (protects erythrocytes and membranes from free radical damage)
Fragile erythrocytes leading to hemolytic anemia. Muscle weakness, posterior column and spinocerebellar tract demyelination

Catalyzes γ-carboxylation of glutamic acid residues on various proteins of blood clotting
Synthesized by intestinal flora
II, VII, IX, X, Proteins C and S
Warfarin --/ VitK
Neonatal hemorrhage with ↑ PT and ↑ aPTT but normal bleeding time
Infancy (because of sterile intestines) or broad spectrum antibiotics
Given to neonates because not in breast milk and prevents hemorrhage

Enzyme activity. Zn fingers in transcription factors
Delayed wound healing, Hypogonadism, ↓ adult hair, Dysgeusia, Anosmia
Predispose to Alcoholic Cirrhosis

EtOH metabolism leads to ↑ NADH/NAD ratio in liver

When NADH high, Pyruvate --> Lactate, Oxaloacetate --> malate

This leads to inhibition of gluconeogenesis and stimulates Fatty Acid Synthesis

Hypoglycemia and Hepatic Fatty Change

Overproduction of lactate --> acidosis

Depletion of oxaloacetate shuts down the TCA cycle, shunting acetyl-CoA into ketone production

Excess malate ↑ NADPH and thus fatty acid synthesis

Kwashiorkor and Marasmus

Protein malnutrition
"MEAL" Malnutrition, Edema, Anemia, Liver
Skin lesions, edema, Liver malfunction (fatty change due to ↓ apolipoprotein synthesis)
Small child with a swollen belly

Energy malnutrition

| Tissue and muscle wasting, loss of subcutaneous fat, edema

Cyto:
EtOH + NAD --> [Alcohol Dehydrogenase] --> Acetaldehyde + NADH
Mito:
Acetaldehyde NAD --> [Acetaldehyde Dehydrogenase] --> Acetate + NADH
NAD is limiting reagent
Zero-Order Kinetics

Inhibits Alcohol Dehydrogenase

| Antidote for methanol or ethylene glycol poisoning

Inhibits Acetaldehyde Dehydrogenase
Alcoholism
Produces Hangover Symptoms

D and K