is total rate of body metabolism

=amount of O2 consumed by body per min

Vitamins B and C (coenzymes, widespread effects)

• cant be stored in body
  thiamin (B1) needed to convert pyruvate to acetyl CoA
• Niacin (B3) and riboflavin (B2) – needed to make FAD and NAD 
• Pyridoxine (B6) – needed for amino acid metabolism 
• Vitamin C – antioxidant 

specialized effects

• Vit A (vision, development), 
• D (Ca2+ metabolism), 
• E (antioxidant), 
• K (blood coagulation)

• Molecules containing an unpaired electron in their outer orbital 
• Highly reactive, oxidizing or reducing other atoms 
• Reactive oxygen species – O2.- and OH. 
• Reactive nitrogen species – NO.

Mitochondria – oxidative phosphorylation

Peroxisomes, NADPH oxidase, and other enzymes

• WBC 
• Destroy bacteria 
• Proliferation of lymphocytes 
• Wound healing – proliferation of fibroblasts 
• Vasodilation by NO.

• Free radicals are highly toxic to cells (especially OH.-) – altering the structures of proteins, nucleic acids, lipids, and other molecules → cell damage → cell mutation or death 
• Promotes apoptosis, aging, inflammatory disease, degenerative, & other diseases & malignant growth

• Endogenous enzymes that neutralize free radicals 
• Superoxide dismutase (SOD), superoxide catalase
• Glutathione peroxidase and glutathione reductase (reduced form)
• Vitamins and others
• B-Carotene, vitamin C, E
• Fruits and vegetables

There is a receptor called PPAR gamma (peroxisom proliferator activated receptor, subtype gamma). This serves as transcription factor. If we increase level of long chain fatty acids in blood, it will go to fat tissues. After birth, those cells become adipocytes, which serve as receptor for PPAR gamma. 

PPARγ – peroxisome proliferator activated receptor, subtype γ

PPARγ functions as transcription factors for activation of genes for differentiation & metabolism

Needed for preadipocyte differentiation – ↑ In circulating fatty acids or prostaglandin (PGJ₂) → bind to PPARγ → ↑ mitosis & differentiation of preadipocytes → ↑ # of adipocytes PPARγ are in the same family as the R’ for thyroid H, vit A and vit D

• Our body is able to maintain a narrow range of our body weight/level of fat. It inhibits too much fat.
• A hypothesis that keeps the level of body fat within a narrow range despite considerable variations in dietary fat intake and physical activity
• Negative feedback loops to defend maintenance of a certain amount of adipose tissue
• Makes it difficult to lose weight

Hormones! 

ex: insulin, GH, thyroid H', adrenal gland H'

• Adipocytes secrete regulatory hormones called adipokines when their PPARγ are activated
• Adipokines regulate hunger, metabolism, and insulin sensitivity
• Adipokines (hormones secreted by adipose tissue) include adiponectin, leptin, TNFα, resistin and retinol binding protein-4 (retinol BP4)

• Energy metabolism- ↑fat tisue→↑leptin secretion→↓leptin levels→diminished immune activities

• Link between adipose tissue and reproductive system, indicating whether adequate energy reserves are present for normal reproductive function
• Leptin may play role in timing of puberty
• Amenorrhea of underweight women

has an insulin-sensitizing, antidiabetic effect

is decreated in obseity and type II diabetes

w/h²

• w=weight in kilograms
• h=height in meters

1. It secretes neuropeptide Y (NPY) and agouti-related protein )پعپتئدع()آگِ(→↑hunger
2. Secretion of melanocyte stimulating hormone (MSH)→↓hunger
3. ↑circulating energy substrates→↑inMSH and ↓ in NPY and ↓ in agouti-related protein secretions →↓appetite

Endorphins, NE-promote overeating "Enemy, NE-my"
Seretonin-suppresses overating "Serpress"

• actions of Redux, fen-phen-mimic serotonin, now banneddue to cardiac cycle effects 

• Regulate hunger on short-term, meal-to-meal basis
• Ghrelin (stomach) stimulates hunger via effect in arcuate nucleus
• CCK (SI) promotes satiety
• PYY (SI) responds to caloric content of food, reduce appetite for 12 hours (mid-term)

• a satiety factor
• involved in long-term regulation
• Secretion increases as stored fat increases
• Signals body's level of adiposity
• Leptin→↓NPY & agouti-related peptide in arcuate N. →↓ hunger Leptin →↓ MSH →↓hunger

• Absorption of abundant energy, within 4 hr period after eating
• ↑ insulin secretion

Postabsorptive state:

• Fasting state, at least 4 hr after the meal 
• ↑ glucagon secretion

• The rate of deposit and withdrawal of energy substrates, and interconversion of energy substrates; are regulated by hormones 
• Antagonistic effects of insulin, glucagon, GH, T₃, cortisol, and Epi balance anabolism and catabolism

• Glucose in excess → ↑ glycogenesis in liver & skeletal muscles
• If excess exists after full glycogenesis → ↑ lipogenesis
• Fatty acids in excess → ↑ lipogenesis
• Fatty acids in excess → ↑ protein synthesis 

• Gluconeogenesis – formation of glucose from amino acids, glycerol, lactate 
• Ketogenesis - formation of ketone bodies

• Glycolysis 
• TCA cycle (citric acid cycle, Kreb’s cycle)--for pyruvate and fatty acid

• b cells - 60%, secrete insulin 
• a cells - 25%, secrete glucagon 
• d cells - somatostatin

Secretion of insulin – in response to ↑ blood [glucose] (main effect), ↑ blood [amino acid] (lesser)

• Blood [glucose] ↑→ glucose binds to GLUT2 R’ in b cells ↑→ insulin secretion → glucose enters cells by facilitated diffusion
• Normal fasting [glucose] is 65–105 mg/dl
• Insulin and glucagon normally prevent levels from rising above 170 mg/dl after meals or falling below 50 mg/dl between meals

Effect of autonomic nerves

• Sympathetic effect - “fight or flight”, enhances glucagon secretion, stress hyperglycemia 
• Parasympathetic effect - “rest and repair”, “+” insulin 

Effect of hormones

• GIP (glucose-dep. insulinotropic peptide) →↑ insulin secretion 
• Glucose ingestion vs. i.v. glucose injection
• Makes more insulin secreted by directly contacting small intestine, which is a stronger effect than simply directly injecting glucose into circulation...that's because of this hormone.
• CCK →↑ insulin secretion 

• ↑Glycogenolysis in the liver 
• ↑ Gluconeogenesis 
• ↑Lipolysis and ketogenesis
• Skeletal muscle, heart, liver, and kidneys use fatty acids as major source of fuel (hormone-sensitive lipase)

• A person drinks a glucose solution and blood samples are taken periodically 
• Normal person’s rise in blood [glucose] after drinking solution is reversed to normal in 2 hrs 
• Blood [glucose] levels in patients with diabetes mellitus remain > 200 mg/dl 2 hr following glucose ingestion 
• The test measures: 
• Ability of insulin to lower blood glucose (insulin-resistance) 
• Ability of b cells to secrete insulin (insulin secretion) 
• Reactive hypoglycemia 
• Symptoms of hypoglycemia 
• Insulin injections → insulin shock

• Diabetes mellitus
• AKA type I DM, juvenile-onset DM
• Autoimmunity (virus)
• Hyperglycemia
• Osmotic diuresis

chronic ↑ in blood [glucose]

• Also called type I DM, juvenile-onset DM 
• Occurs at juvenile age, account for 5% of DM patients 

• Killer T cells target glutamate decarboxylase in b cells → b cells destroyed, a cells active → low insulin, high glucagon

• Lack of insulin → glucose cannot enter the adipose cells 
• ↑Glucagon/insulin ratio → ↑ glycogenolysis in liver → ↑ glucose exit into blood from liver 
• Lack of insulin → rate of lipolysis > rate of lipogenesis → ↑ fatty acid in blood 
• Fatty acids converted to ketone bodies → hyperketonemia (ketone bodies contain acids) → ketoacidosis (ketone bodies contain acetone)→ coma (caused by acid base inbalance)
• Also causes osmotic diuresis → glucosuria, dehydration
• If someone has diabetes milllitus, they will: urine a lot, drink a lot, cell is hungry so they will eat a lot.  

• Cells fail to respond to the normal actions of insulin
• When fat and muscle cells fail to respond adequately to circulating insulin, blood glucose levels rise

Slow to develop, genetic factors play a role

Occurs most often in mid-age people who are overweight

Diet-↑polyunsaturated fatty acids→↑cell membrane fluidity→↑insulin R'#→↑affinity of insulin to its receptors→↓insulin resistance (?)

Change in lifestyle:

• Increase exercise→↑GLUT-4 in the skeletal muscle cells
• Weight reduction-↑ fiber in diet, ↓ saturated fat

Secretes epinephrine and norepinephrine

• Used for fight or flight (short-term stress)→need glucose for CNS and skeletal muscles
• Stimulates glycogenolysis→hyperglycemia
• Stimulates lipolysis-similar to glucagon effects during fasting
• Second messenger-cAMP (similar to glucagon)

• Secretes glucocorticoids (e.g. cortisol) sitmulated by ACTH in response to long-term stress
• Promotes glucagon secretion → glycogenolysis→hyperglycemia
• Promotes lipolysis, ketogenesis, hyperketoemia
• Promotes protein breakdown, gluconeogenesis

Main form of secretion is T₄, active form is T₃

Basal metabolic rate

Calorigenic effects (↑ metabolic heat) and cold adaptation 

• Protein synthesis, growth of skeleton
• Contributes to proper growth and development of CNS - prenatal to 6 months after birth

secretion-controlled by somatostatin (GHIH) and GHRH

Actions

• ↑growth in children and adolescents. this effect is indirect. first, it stimulates liver to secrete insuline-like growth factor 1, which stimulates growth of cartilage and bone and muscle and other organs protein synthesis growth.
• Effects on bone & muscles, mediated by IGF I, II, (somatomedins)

• It causes adipose tissue lipolysis and release of fatty acids
• Most tissues decreased glucose utilization

Gigantism, dwarfism (if before puberty)

Acromegaly-elongation of jaw and deformities in bones of the face, hands, and feet (if after puberty)

• Bone structure, muscle contraction, neurotransmission, second messenger, membrane permeability
• Hypocalcemia-enhances nerve excitability→muscle spasm (tetanus)

• Bone formation and resorption
• Skeleton also serves as a storage of Ca⁺⁺ & PO₄^-3 as hydrooxyapatite (Ca₁₀(PO₄)(OH)₂)
• Osteoblasts for bone deposition (collagen+Ca⁺⁺) vs. osteoclasts for bone resorption
• Intestinal absorption and urinary excretion

Parathyroid hormone (PTH) - increases blood [Ca²⁺]

• Single most important hormone in the control of blood [Ca²⁺]
• Stimulating bone resorption of Ca²⁺
• Inhibiting renal reabsorption of PO₄^3-
• Promoting formation of (OH)₂ Vit D₃

Over-secretion of PTH→osteoporosis

1,25-Dihydroxyvitamin D₃ [(OH)₂ Vit D₃]

Formation - function of liver and kidney

(OH)₂ Vit D₃ stimulates

• Intestinal absorption of Ca²⁺ & PO₄^3-
• Bone resorption
• Renal reabsorption of Ca⁺⁺ and PO₄^-3 

• Secreted by parafollicular (C) cells 
• Functions – lower plasma Ca⁺⁺ by 
• Reduced bone resoprtion – inhibits osteoclast activity 
• Reduced renal reabsorption – stimulates urinary excretion of Ca⁺⁺ 

• Treatment of osteoporosis 
• Nasal spray – less side effects

• Causes epiphyseal discs (cartilaginous growth plates) to seal (ossify) which stops growth 
• Is necessary for proper bone mineralization & prevention of osteoporosis 
• Stimulates osteoblast activity & suppresses formation of osteoclasts

• Is a lifelong process 
• Bone resorption vs. bone formation (ossification) 
• Bone remodeling cycle 
• In 1st year of life – ~100% replacement In adults – ~10% per year
• Ossification (osteogenesis) – the process of formation of new bone by action of osteoblasts 
• Deposit Ca2+ on bone matrix 
• Stimulated GH, thyroid hormones & sex hormones (estrogens & androgens) 
• Osteoclasts – typically multinucleated, are the only cells to be capable of resorbing bone