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Definition of RDA

RDA = Recommended Dietary Allowance; average daily intake that meets the needs of almost all healthy people, about 97–98%. age and gender specific

Definition of EAR

EAR = Estimated Average Requirement; intake that meets the needs of 50% of healthy people.

Definition of AI

AI = Adequate Intake; used when there is not enough evidence to make an EAR/RDA.

Definition of UL

UL = Tolerable Upper Intake Level; highest daily intake unlikely to cause harm. Going above this increases toxicity risk.

Definition of DV

DV = Daily Value; value used on nutrition labels to compare nutrient amounts in foods.

Definition of NE

NE = Niacin Equivalent; used for niacin because niacin can come from diet or from tryptophan. 60 mg tryptophan = 1 mg niacin equivalent.

Innervations of the GI tract: (extrinsic) parasympathetic nervous system

Parasympathetic nervous system usually increases GI activity, secretion, and motility. The small intestine receives parasympathetic innervation through the vagus nerve.

Innervations of the GI tract: sympathetic nervous system

Sympathetic nervous system usually decreases GI activity, secretion, and motility. The small intestine receives sympathetic innervation from thoracic splanchnic nerves.

Innervations of the GI tract: enteric nervous system

Enteric nervous system is the “in-house” nervous system of the GI tract. It includes the myenteric plexus and submucosal plexus.

4 main layers: mucosa, submucosa, muscularis externa, serosa/adventitia.
Mucosa has 3 parts: mucosal membrane, lamina propria, muscularis mucosa.

Also know the plexuses:

Submucosal/Meissner’s plexus is in the submucosa and controls secretions/local blood flow.
Myenteric/Auerbach’s plexus is between muscle layers and controls motility/peristalsis

The layers of tissue surrounding the GI tract and their roles: mucosa

Mucosa = innermost layer that touches food. Its role is to secrete, absorb, and digest. It includes the mucosal membrane, lamina propria, and muscularis mucosa.

The layers of tissue surrounding the GI tract and their roles: lamina propria

Lamina propria = connective tissue and lymphoid tissue within the mucosa. It helps protect against microorganisms because it contains immune cells.

The layers of tissue surrounding the GI tract and their roles: submucosa

Submucosa = connective tissue, blood vessels, lymph vessels, lymphoid tissue, and submucosal plexus. It helps control secretions and local blood flow.

The layers of tissue surrounding the GI tract and their roles: muscularis externa

Muscularis externa = muscle layer responsible for segmentation and peristalsis. Thickened areas form sphincters.

The layers of tissue surrounding the GI tract and their roles: serosa/adventitia

Serosa/adventitia = outermost layer. It is called adventitia in the esophagus.

The location of the 2 plexuses within the tissue layers: myenteric plexus

Myenteric plexus/Auerbach’s plexus = located between muscle layers of the muscularis externa. It controls GI motility and peristalsis.

The location of the 2 plexuses within the tissue layers: submucosal plexus

Submucosal plexus/Meissner’s plexus = located in the submucosa. It controls GI secretions and local blood flow.

All secretions and substances needed for digestion: HCl

HCl = hydrochloric acid secreted by parietal cells. It lowers stomach pH, converts pepsinogen to pepsin, denatures proteins, kills bacteria, and releases nutrients from complexes.

All secretions and substances needed for digestion: intrinsic factor

Intrinsic factor = secreted by parietal cells. It is needed for vitamin B12 absorption.

All secretions and substances needed for digestion: pepsinogen

Pepsinogen = inactive protein-digesting enzyme secreted by chief cells. It is activated by HCl into pepsin.

All secretions and substances needed for digestion: pepsin

Pepsin = active enzyme formed from pepsinogen by HCl. It digests proteins in the stomach.

All secretions and substances needed for digestion: gastric lipase

Gastric lipase = secreted by chief cells. It breaks down triacylglycerols and contributes to lipid digestion.

All secretions and substances needed for digestion: mucus

Mucus = protective and lubricating secretion. It protects the stomach lining from acid and digestive enzymes.

All secretions and substances needed for digestion: bicarbonate

Bicarbonate = neutralizes acid. It helps protect the stomach lining and neutralizes acidic chyme in the small intestine.

All secretions and substances needed for digestion: gastrin

Gastrin = hormone released from stomach enteroendocrine cells. It stimulates stomach acid/HCl secretion.

All secretions and substances needed for digestion: secretin

Secretin = hormone released by the duodenum in response to acidic chyme. It stimulates pancreatic bicarbonate release.

All secretions and substances needed for digestion: CCK

CCK = cholecystokinin; released in response to fat/protein in the small intestine. It stimulates gallbladder bile release and pancreatic enzyme/bicarbonate release and slows GI motility.

All secretions and substances needed for digestion: bile

Bile = produced by the liver and stored in the gallbladder. It emulsifies fats so they can mix with water and be digested/absorbed.

All secretions and substances needed for digestion: pancreatic enzymes

Pancreatic enzymes = enzymes released into the small intestine that digest carbohydrates, proteins, and fats.

All secretions and substances needed for digestion: trypsinogen/trypsin

Trypsinogen = inactive pancreatic enzyme. Trypsin = active enzyme that helps digest proteins into smaller peptides/amino acids.

Anatomy of the enterocyte: enterocyte

Enterocyte = absorptive intestinal cell that absorbs nutrients from the intestinal lumen.

Anatomy of the enterocyte: apical side/brush border

Apical side/brush border = side of the enterocyte facing the intestinal lumen/chyme/food. It contains microvilli, enzymes, and transporters.

Anatomy of the enterocyte: basolateral side

Basolateral side = side of the enterocyte facing blood/lymph. Nutrients exit the enterocyte through this side after absorption.

Differences between fat-soluble and water-soluble vitamins: absorption

Water-soluble vitamins are absorbed directly into blood. Fat-soluble vitamins are absorbed first into lymph, then blood, and require bile.

Differences between fat-soluble and water-soluble vitamins: transport

Water-soluble vitamins travel more freely in blood. Fat-soluble vitamins often need transport proteins.

Differences between fat-soluble and water-soluble vitamins: storage

Water-soluble vitamins are stored less. Fat-soluble vitamins are stored in fat-associated tissues.

Differences between fat-soluble and water-soluble vitamins: excretion

Water-soluble vitamins are more easily excreted in urine by kidneys. Fat-soluble vitamins are less easily excreted.

Differences between fat-soluble and water-soluble vitamins: toxicity

Water-soluble vitamin toxicity is possible from supplements but generally less likely. Fat-soluble vitamin toxicity is more likely because they remain stored longer.

Differences between fat-soluble and water-soluble vitamins: how often needed

Water-soluble vitamins are needed frequently, about every 1–3 days. Fat-soluble vitamins are needed less often, over weeks or months.

The forms of vitamin C and oxidation/reduction reactions: ascorbic acid/ascorbate

Ascorbic acid/ascorbate = reduced active form of vitamin C. At physiological pH, vitamin C is mostly ascorbate.

The forms of vitamin C and oxidation/reduction reactions: ascorbyl radical

Ascorbyl radical = intermediate oxidized form of vitamin C. It is missing 1 electron and 1 hydrogen.

The forms of vitamin C and oxidation/reduction reactions: dehydroascorbic acid/DHA

Dehydroascorbic acid/DHA = oxidized form of vitamin C missing 2 electrons and 2 hydrogens. DHA still has vitamin activity because it can be reduced back to ascorbate.

The forms of vitamin C and oxidation/reduction reactions: glutathione

GSH/glutathione reduces DHA back to vitamin C and becomes oxidized to GSSG.

The forms of vitamin C and oxidation/reduction reactions: antioxidant role

Vitamin C acts as an antioxidant because it can donate and accept electrons/hydrogens.

Synthesis of FMN: pathway

Riboflavin → FMN → FAD.

Synthesis of FMN: flavokinase

Flavokinase converts riboflavin to FMN.

Synthesis of FMN: FAD synthetase

FAD synthetase converts FMN to FAD.

Synthesis of FMN: hormones that stimulate conversion

ACTH, aldosterone, and thyroid hormones stimulate conversion of riboflavin to its coenzyme forms.

NAD synthesis in general steps

Tryptophan → kynurenine pathway → nicotinic acid/nicotinamide → NAD → NADP.

NAD synthesis: amino acid required

Tryptophan is the amino acid used to make niacin/NAD.

NAD synthesis: vitamin and mineral requirements

Riboflavin (B2), vitamin B6/PLP, and iron are required for efficient NAD synthesis from tryptophan.

NAD synthesis: tryptophan conversion

60 mg tryptophan = 1 mg niacin equivalent.

NAD synthesis: is riboflavin needed?

Yes. Riboflavin is needed to help make NAD from tryptophan.

Functions of each vitamin: Vitamin C

Vitamin C functions: antioxidant/reducing agent; collagen synthesis; carnitine synthesis; neurotransmitter synthesis; tyrosine metabolism/catabolism; enhances non-heme iron absorption.

If vitamin C is required for an enzyme, what does that enzyme/protein do?

Prolyl hydroxylase and lysyl hydroxylase hydroxylate proline and lysine for collagen structure. Carnitine synthesis enzymes help make carnitine for fatty acid transport into mitochondria. Vitamin C supports tyrosine metabolism and neurotransmitter synthesis and keeps iron/copper cofactors reduced.

Functions of each vitamin: Thiamin (B1)

Thiamin functions as TPP/TDP in pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain α-ketoacid dehydrogenase, transketolase, and nervous system function.

If thiamin is required for an enzyme, what does that enzyme/protein do?

Pyruvate dehydrogenase converts pyruvate to acetyl-CoA. α-ketoglutarate dehydrogenase converts α-ketoglutarate to succinyl-CoA. Branched-chain α-ketoacid dehydrogenase breaks down branched-chain amino acids. Transketolase transfers 2-carbon units in the pentose phosphate pathway to help make ribose sugars and NADPH.

Functions of each vitamin: Niacin (B3)

Niacin functions as NAD and NADP in redox reactions, energy metabolism, glycolysis, pyruvate oxidation, TCA cycle, beta-oxidation, electron transport chain, fatty acid synthesis, cholesterol/steroid synthesis, DNA synthesis, and vitamin C/glutathione regeneration.

If niacin is required for an enzyme, what does that enzyme/protein do?

NAD accepts electrons in catabolic reactions and becomes NADH. NADH carries electrons to the ETC to make ATP. NADP/NADPH is used in anabolic reactions like fatty acid, cholesterol, and steroid synthesis.

Functions of each vitamin: Riboflavin (B2)

Riboflavin functions as FMN and FAD in redox reactions, energy production, TCA cycle, electron transport chain, beta-oxidation, vitamin B6 activation, niacin synthesis from tryptophan, vitamin A metabolism, and glutathione antioxidant system.

If riboflavin is required for an enzyme, what does that enzyme/protein do?

Pyridoxine phosphate oxidase uses FMN to convert PNP/PMP into PLP. Succinate dehydrogenase uses FAD in TCA/ETC. L-amino acid oxidase uses FMN to convert amino acids into keto acids. Glutathione reductase is FAD-dependent and regenerates reduced glutathione/GSH.

Functions of each vitamin: Pantothenic Acid (B5)

Pantothenic acid functions as part of CoA and 4′-phosphopantetheine in acyl transfer reactions, acetylation/acylation, fatty acid synthesis, cholesterol synthesis, ketone body formation, and gene expression.

If pantothenic acid is required for an enzyme/protein, what does that enzyme/protein do?

CoA carries acetyl and acyl groups. Acetyl-CoA enters the TCA cycle and is used in fatty acid synthesis. Malonyl-CoA is used in fatty acid synthesis. Acyl carrier protein/ACP carries the growing fatty acid chain during fatty acid synthesis.

Functions of each vitamin: Biotin (B7)

Biotin functions as a coenzyme carrier of activated bicarbonate/CO₂ in carboxylation reactions, gluconeogenesis, fatty acid synthesis, amino acid metabolism, gene regulation, and histone biotinylation.

If biotin is required for an enzyme, what does that enzyme/protein do?

Pyruvate carboxylase converts pyruvate to oxaloacetate. Acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA. Propionyl-CoA carboxylase helps metabolize odd-chain fatty acids and some amino acids. β-methylcrotonyl-CoA carboxylase is involved in leucine metabolism.

Specifics of niacin absorption: digestion

Niacin food forms include NAD and NADP, which must be digested before absorption. NADP → NAD → nicotinamide → absorbed.

Specifics of niacin absorption: enzymes

Niacin digestion uses pyrophosphatase and glycohydrolase.

Specifics of niacin absorption: absorbed forms

Absorbed forms of niacin are nicotinamide and nicotinic acid.

Specifics of niacin absorption: absorption method

Niacin is absorbed mostly in the small intestine. Low concentrations use carrier-mediated absorption. High pharmacologic doses use diffusion.

Specifics of biotin uptake and digestion: food forms

Biotin in food can be free or protein-bound.

Specifics of biotin uptake and digestion: digestion

Protein-bound biotin is digested by pepsin and intestinal proteases to form free biotin and/or biocytin.

Specifics of biotin uptake and digestion: biotinidase

Biotinidase breaks biocytin into free biotin + lysine.

Specifics of biotin uptake and digestion: absorbed form

Only free biotin can be absorbed.

Specifics of biotin uptake and digestion: absorption

Biotin is absorbed by SMVT in the proximal small intestine and colon. High doses can use passive diffusion.

Specifics of pantothenic acid absorption and digestion: food forms

Most dietary pantothenic acid is bound as CoA or 4′-phosphopantetheine.

Specifics of pantothenic acid absorption and digestion: digestion pathway

Digestion pathway: CoA → 4′-phosphopantetheine → pantetheine → pantothenic acid.

Specifics of pantothenic acid absorption and digestion: enzymes

Enzymes for pantothenic acid digestion are pyrophosphatase, phosphatase, and pantetheinase.

Specifics of pantothenic acid absorption and digestion: absorption

Pantothenic acid is absorbed mostly in the jejunum. Normal/low concentration uses SMVT. High concentration uses passive diffusion.

Specifics of pantothenic acid absorption and digestion: amount absorbed

About 50% of pantothenic acid is absorbed. High supplement doses reduce absorption efficiency.

Riboflavin absorption: absorbable form

Only free riboflavin is absorbable.

Riboflavin absorption: digestion

FAD → FMN by FAD pyrophosphatase. FMN → riboflavin by FMN phosphatase.

Riboflavin absorption: protein-bound riboflavin

Protein-bound riboflavin must be released by HCl and digestive proteases.

Riboflavin absorption: transport

Free riboflavin enters enterocytes using RFVT3 and leaves through RFVT1 and RFVT2.

Riboflavin absorption: high doses

High doses of riboflavin can be absorbed by diffusion.

Transporters needed for digestion and absorption: SVCT1

SVCT1 = sodium-dependent vitamin C transporter 1; transports ascorbic acid/ascorbate and is the major intestinal vitamin C absorption transporter.

Transporters needed for digestion and absorption: SVCT2

SVCT2 = sodium-dependent vitamin C transporter 2; transports ascorbic acid/ascorbate into tissues with high need.

Transporters needed for digestion and absorption: GLUT1–4

GLUT1–4 = transport DHA, the oxidized form of vitamin C.

Transporters needed for digestion and absorption: ThTr1

ThTr1 = thiamin transporter 1; high-capacity thiamin transporter involved in uptake/transport.

Transporters needed for digestion and absorption: ThTr2

ThTr2 = thiamin transporter 2; higher-specificity thiamin transporter that increases when thiamin intake is low.

Transporters needed for digestion and absorption: OCT1/OCT3

OCT1/OCT3 = organic cation transporters involved in thiamin tissue uptake.

Transporters needed for digestion and absorption: RFVT3

RFVT3 = riboflavin vitamin transporter 3; transports free riboflavin into enterocytes.

Transporters needed for digestion and absorption: RFVT1/RFVT2

RFVT1/RFVT2 = riboflavin transporters that help export riboflavin and help with tissue transport.

Transporters needed for digestion and absorption: SMVT

SMVT = sodium-dependent multivitamin transporter; transports pantothenic acid, biotin, and lipoic acid.

Structural components of thiamin

Thiamin structure = pyrimidine ring + thiazole ring + methylene bridge. Active form = TPP/TDP.

Structural components of thiamin: food forms

Plant foods mostly have non-phosphorylated/free thiamin. Animal foods mostly have phosphorylated TDP.

What decreases thiamin absorption/availability?

Alcohol blocks ThTr1 and ThTr2 expression. Thiaminases in raw fish cleave/destroy thiamin. Polyhydroxyphenols in coffee, tea, and some fruits/vegetables destroy thiamin. Heat and alkaline pH destroy thiamin.

What increases/protects thiamin absorption/availability?

Cooking inactivates thiaminases. Vitamin C can prevent thiamin destruction by polyhydroxyphenols.

Details of how thiamin is absorbed and digested

Phosphorylated thiamin must be dephosphorylated by phosphatases. It is absorbed in the duodenum, jejunum, and colon. Low intake uses carrier-mediated active transport. High intake uses diffusion. Saturates around 5 mg. Enters blood within 1–2 hours.

Vitamin C excretion

Most excess vitamin C is excreted in urine. Plasma saturation occurs around about 500 mg or lower. Excess is excreted within about 6 hours. Some excess is metabolized in liver and kidney.

What can happen when excess vitamin C is consumed?

Excess vitamin C can cause nausea, abdominal cramps, osmotic diarrhea, increased oxalic acid/kidney stone risk, worsen iron overload disorders because vitamin C increases non-heme iron absorption, and interfere with some lab tests.