Vitamins: Fat-Soluble, Water-Soluble and Antioxidant

Vitamins

• Substances needed in small amounts for growth and health.
• They are essential for using proteins and carbohydrates in the diet.
• Vitamins act as coenzymes in energy-related reactions, such as B vitamins in glucose oxidation.
• Most vitamins are not made in the body, with exceptions like vitamin D (skin), some B vitamins + vitamin K (intestinal bacteria), and carotene (provitamin for vitamin A).
• Vitamins are divided into two classes: fat-soluble and water-soluble.

Fat-Soluble Vitamins

• Include vitamins A, D, E, and K.
• Absorbed with dietary lipids and can be stored in the body, except for vitamin K.
• Storing fat-soluble vitamins can lead to toxicity problems, especially with vitamin A.

Water-Soluble Vitamins

• Include B-complex vitamins and vitamin C.
• Absorbed with water, except for vitamin B12.
• Water-soluble vitamins have insignificant storage in the body.

Antioxidant Vitamins

• Vitamins A, C, and E are classified as antioxidants
• They disarm tissue-damaging free radicals by providing them with unpaired electrons
• This action protects against tissue damage and chronic diseases like cataracts, cardiovascular disease, arthritis, and cancer.

Minerals

• Moderate amounts of seven minerals are needed: calcium, phosphorus, potassium, sulfur, sodium, chloride, magnesium
• Trace amounts of other minerals are needed: iron, iodine, maganese, copper, zinc, cobalt, fluorine, selenium, chromium.
• Minerals constitute ~4% of body weight, with calcium and phosphorus making up most of this as bone salts.
• Iron is needed for hemoglobin, sodium and chloride for osmolarity/water balance and cell stimulation, and iodine for thyroid hormone.
• Critical balance must be maintained between mineral intake and excretion, achievable through vegetables, milk & some meats

Water Functions

• Carries nutrients throughout the body and cleanses blood of wastes.
• Water is a solvent for minerals, vitamins, amino acids, glucose, etc.
• It actively participates in chemical reactions.
• Water acts as a lubricant around joints.
• It is a shock absorber for eyes, the spinal cord, joints and the amniotic sac.
• Water aids in body temperature regulation.

Anabolic and Catabolic Metabolic Processes

• Nutrients are digested into absorbable units in the GI tract and then absorbed into the blood to be transported to tissue cells.
• In tissue cells nutrients are either built into macromolecules in anabolism, or partially broken down in catabolism.
• Glycolysis is the major catoblic pathway and ends with pyruvate.
• Oxidative breakdown of stage 2 products occurs in the mitochondria releasing CO2.
• The H atoms removed are ultimately delivered to molecular oxygen, forming water.
• Some of the energy released is used to form APT.
• The citric acid cycle and oxidative phosphorylation are the major pathways.

Carbohydrate Metabolic Pathways

• Glycolysis converts glucose to pyruvic acid.
• Glycogenesis polymerizes glucose to form glycogen.
• Glycogenolysis hydrolyzes glycogen to glucose monomers.
• Gluconeogenesis creates glucose from non-carbohydrate precursors.
• The two substrates for gluconeogenesis are amino acids and glycerol.

Lipid Metabolic

• Fatty acids undergo beta-oxidation.
• Ketone bodies are produced during fat metabolism.
• The possible fates for glycerol and fatty acids are as follows: Lipolysis -> Glycerol, Fatty acids -> Lipogenesis + Ketogenesis

Amino Acid Metabolism

• Amino acids build proteins or provide energy when needed.
• Excess amino acids are burned for energy or stored as fats
• When blood glucose is low, amino acids can be converted to keto acid building blocks for glucose.
• Transamination allows hepatic cells to produce nonessential amino acids as needed

Transamination

• An amine group switches from an amino acid to a keto acid.

Oxidative Deamination

• The amine group of glutamic acid is removed as ammonia and combined with CO2 to form urea

Keto Acid Modifications

• The keto acids formed during transamination are altered to enter the citric acid cycle.

Interconversion of Carbohydrates, Fats and Proteins

• Dietary intake of proteins, carbs, and fats are broken down into amino acids, glucose and triglycerides.
• Glucose in the liver is used to create glycogen.
• Glycerol and fatty acids are derived from fats.
• Excess Acetyl CoA results in the production of Keytone bodies

Absorptive and Postabsorptive States

• Absorptive State: The time shortly after eating up to 4 hours - during which nutrients enter the circulation and blood glucose levels rise.
• Postabsorptive State: The time when the GI tract is empty - breakdown of food reserves meet energy needs and maintain blood glucose levels.
• During the absorptive state, anabolic processes exceed catabolic processes.
• During the absorptive state, glucose is the major metabolic fuel.
• During the absorptive state, dietary amino acids and fats remake degraded body protein or fat, or make new protein.
• Any excess metabolites, regardless of source, are transformed into fat.

Absorptive State Pathways

• In all pathways glucose is converted to create ATP.
• Leftover proteins are converted to triglycerides and stored.
• Glycogen stores in the liver and muscle tissue are replenished.

Role of Insulin

• Insulin directs essentially all events of absorptive state
• It is produced by beta cells of islets of Langerhans (endocrine pancreas; ~2% of gland)
• Insulin secretion is stimulated by a rise in blood glucose.
• It is also stimulated by increased blood amino acids.
• Insulin activates carrier-mediated facilitated diffusion of glucose into cells by 15-20x within min, especially in skeletal muscle and adipose tissue.
• Insulin is not needed for glucose entry into liver, kidney, brain, intestinal epithelial cells.
• These have easy access to glucose regardless of insulin levels.

Insulin Structure and Synthesis

• Insulin Structure: small (51 aa) protein consisting of 2 amino acid chains connected by disulfide bonds.
• Insulin is initially synthesized as proinsulin; the middle portion is excised (C-peptide) before release.

Glucose Transporters

• GLUT-4 transporter is located in adipose tissue and muscle cells and are insulin-dependent, while GLUT-2 transporter is located in cells of the liver and pancreas and have a lower affinity for glucose and are not insulin-dependent
• GLUT-1transporters do not require insulin and are located in red blood cells and cells lining the blood vessels.

Insulin Action

(1) Enhances glucose oxidation for energy (2) Stimulates conversion of glucose to glycogen and to triglycerides (3) Increased active uptake of amino acids and promotes protein synthesis (4) Inhibits liver enzymes that promote gluconeogenesis and/or glyogenolysis

• Insulin is an anabolic, hypoglycemic hormone.
• It lowers blood glucose levels by stimulating cells to use it for energy or store it.

The Postabsorptive State Goal

• Primary objective is to maintain a blood glucose level within the homeostatic range (70-110 mg glucose/100 ml) during times of no food intake.
• Important because the brain must use glucose as its energy source.

Glucose Avaliability During Postabsorptive State

• Events are geared toward sparing glucose for brain cells and making more glucose available to the circulatory system.
• Sources are stored glycogen, tissue proteins, fat (really only glycerol!)

Glycogenolysis

In Liver

• Liver has ~100 g of glycogen reserves and is the first source of absorptive glucose
• The liver maintain blood glucose for ~4 h during postabsorptive state

In Skeletal Muscle

• Has ~100 g of glycogen reserves.
• It is converted to pyruvic acid or lactic acid to blood and then to liver to glucose.
• Skeletal muscle is an indirect source of blood glucose

Lipolysis

In Adipose Tissues and Liver

• Adipose tissue & liver cells produce glycerol by lipolysis.
• Liver converts glycerol to glucose (gluconeogenesis).
• Free fatty acids can only feed into the Kreb's cycle

Catabolism of Cellular Protein

• Last resort, is only used if fasting is prolonged (glycogen & fat stores become depleted) and during stress (secretion of glucocorticoids).
• Amino acids get deaminated & converted to flucose in the liver.

Glucose Sparing During Postabsorptive State

• Using noncarbohydrate fuel molecules (esp. fats) to conserve glucose.
• As body moves into postabsorptive state, all tissues & organs except the brain switch to using fats as a major energy source.
• Lipolysis in adipose tissue: FFA to tissue cells → oxidized for energy
• Liver oxidizes FFA to ketone bodies, which get released into blood & used by some tissues for energy
• After 4 - 5 days, the brain starts to use some ketone bodies.

Hormonal and Neural Controls During Postabsorptive State

• It is an interaction of sympathetic nervous system with several hormones to regulate postabsorptive state.
• Initiated by a drop of glucose in blood..
• Decreased blood glucose stimulates secretion of glucagon
• Glucagon is a 29-amino acid polypeptide hormone produced by alpha cells of pancreatic islets of Langerhans
• It is a potent hyperglycemic agent where one molecule of glucagon causes the release of 100 million molecules of glucose into blood!
• Major target of glucagon is the liver and adipose tissue.
• Adipose cell stimulate lipolysis, causing a release of FFA & glycerol into the blood.

Sympathetic Reactions During Postabsorptive State

• Responds to sudden drop in blood glucose.
• Bodily injury anxiety, anger , other stressors associate with fight-or-flight response.
• Stimulates lipolysis & fat mobilization, stimulates glycogenolysis.

Epinephrine During Postabsorptive State

• Released from adrenal medulla
• Stimulates glycogenolysis, lipolysis & fat mobilization, stimulates gluconeogenesis.

Adrenal Hormones

• The adrenal cortex secretes glucocorticoid cortisol which is to life.
• The adrenal cortex stimulates lipolysis & fat mobilization, stimulates gluconeogenesis, stimulates protein catabolism.
• Normally, the glucocorticoids help the body adapt to external changes and intermittent food intake by keeping blood sugar levels fairly constant.

Diabetes Mellitus

• It is a metabolic disorder stemming from lack/absence of insulin, insulin resistance, or both.
• Can result in a significant long-term sequelae, particularly damage, dysfunction and failure of various organs - especially the kidney, eye, nerves, heart and blood vessels.
• Hyperglycemia results from a glucose uptake that isn't sufficient to meet needs.
• This leads to an increase fat output from liver with less removal from blood, and a reduced output of amino acids from liver.

Types of Diabetes Mellitus

(1) type 1: insulin-dependent diabetes mellitus (IDDM) due to a destruction of beta cells (2) type 2: non-insulin-dependent diabetes mellitus (NIDDM), caused an insulin resistance leading to reduced insulin levels.