Biology 2402 AP II

Chemical reactions occur in series.... the product of one reaction becomes the substrate for another.

Determined by concentration of enzymes and the rate is determined by the limiting or slowest step in the reaction, also called the rate limiting step.

The energy liberated by complete oxidation of food is measured in calories/mole.
A calorie is the quantity of heat needed to raise the temperature of 1 gram of H20, 1 degree Celsius

A Kilocalorie (C) is equal to 1000 calories (c).

Metabolism is all the biochemical reactions in the body and involve the following processes :

Reactions ::

oxidation reaction --> lose electrons (e-), lose E

reduction reactions --> gain electrons (e-), gain E

An oxidation/reduction reaction is called a REDOX reaction

1. catalyzed by enzymes

2. coenzymes available as reversible hydrogen ion (H+) acceptors/donators. Examples of coenzymes are B vitamins nicotin (NAD) and flavin (FAD).

ATP synthesis.... Energy captured in high E bonds by

1. substrate level phosphorylation B> the phosphate is added directly, occurs in the cytoplasm & mitochondria

2. oxidative phosphorylation : by the e- transport system in the mitochondria.

ATP is adenine + ribose + 3 phosphates

AMP + P --> ADP , ADP + P --> ATP

ADP becomes the rate limiting step for almost all reactions

Chemical reactions also involve inter conversions, that is making new molecules from old, therefore synthesis reactions using E.

Nutrients :: 6 groups

Carbohydrates (CH2O), Fats, Proteins, Nucleic acids, Vitamins, Minerals, H20

Essential nutrients : those that cannot be synthesized and are required in the diet.

Nonessential nutrients: those that can be made in the body from essential nutrients.

I. Carbohydrates (CH2O) ::

source....primarily from plants

a. sugars....... milk, honey, fruits

b. starches .... grains, vegetables; cellulose --> nondigestible fiber

Glucose is the primary body fuel and is MOST ALWAYS the final product for transport into the cell.

CH2O digestion starts in the mouth with salivary amylase and continues in the stomach until the pH = 4.
Then it continues in the small intestine with pancreatic amylase and brush border enzymes to complete the breakdown. Absorbed in the portal venous system of the SI

Transport into cells involves one of two processes ::

1. facilitated diffusion :: protein carrier in cell membrane, moves glucose along its concentration gradient (from high to low). NO ENERGY is used.

Transport is enhanced by insulin, to increase the rate of glucose transport into the cell.

2. Co-transport with Na+. Uses energy to pump Na+ occurs in the gi epithelium and renal tubules.

Once in the cell :: glucose is trapped by phosphorylation to form glucose 6 phosphate, and is an IRREVERSIBLE reaction , EXCEPT in cells that have the enzyme to reverse the process.

These cells are ::

1. liver

2. gi epithelium

3. renal tubules

The captured glucose may be used for E or stored.

If used for E, then ultimately becomes Glucose + O2 ---> H20 + CO2 + ATP + Heat

IF stored, will become glycogen by a process called :Glycogenesis.

All cells can store glucose. The majority of the glycogen storage is located in the liver and muscle. To retrieve stored glucose (glycogen), the process is called Glycogenolysis and is stimulated by the hormone glucagon from the alpha cells of the pancreatic islets. This hormone does this by stimulation of enzyme activation by formation of cAMP (cyclic AMP).

METABOLIC PATHWAYS FOR GLUCOSE ::

1. Glycolysis :: occurs in the cytoplasm, anaerobic glucose is split into 2 3carbon molecule and involve sugar activation, sugar cleavage (2, 3Carbon), and sugar oxidation (lose e-) with the final products and end results of glycolysis that are :

a. 2 pyruvic acid molecules

b. 2 NADH + H

c. 2 net ATP (4 were made, 2 were used)

Cofactor examples include ::

cytochromes (iron pigments)

vitamins (flavin)

c. e- are shuttled until reaching the last part of the transport chain :

Cytochrome A3 (cytochrome oxidase). At this point oxygen becomes the final e- acceptor.

d. H+ is removed from the coenzyme & combine with oxygen to form H2O.

Energy is released as e- goes through the chain, and use to attach phosphate to ADP (ADP + P --> ATP). Flow of e- is based on a proton gradient because ::

1. H+ ions are pumped from the inner matrix to the area between the inner and outer membrane so the inner matrix is more negative (-) and (+) between the membranes

2. High concentrations of H+ are maintained since the crista are impermeable to H+ This creates a strong negative electric potential needed for e- transport. IF the gradient is gone, e- transport stops.

TOTAL ATP production for each molecule of glucose = 38 ATP

Control of glycolysis is based on negative feedback for the enzymes and the levels of AMP/ADP/ATP and the availability of ADP and citrate ion

Glucose is converted to glycogen for storage first, then when cells are saturated, will be stored as fat in the liver or adipose tissue. Processes involved ::

Glucose 6 phosphate --> store :: glycogenesis

Alternate pathway for glucose metabolism occurs in the liver and fat cells and involves the PENTOSE-PHOSPHATE pathway. Glucose is eventually converted to CO2 and H20 with ATP production.

Homeostatic mechanisms will try to maintain blood glucose levels around 90 mg/dl.

Range is 70 mg/dl to 120 mg/dl for most mammals.

Problems :: high blood glucose (Hyperglycemia), low blood glucose (hypoglycemia)

Lipids : Neutral fats (triglycerides), phospholipids, cholesterol and prostaglandins.

Various functions ::

Triglycerides :: energy source, storage --> cushion, temp

Phospholipids :: cell membrane, transport, myelin sheath, clotting factors (thromboplastin)

Cholesterol :: cell membrane, bile salts, steroid hormones, skin to prevent H2O loss

Prostaglandins:: local hormones

Fats :: digestion by pancreatic lipase, emulsified by bile salts

Triglycerides are broken into 2 Fatty Acids (FA) and one monglyceride and mixed with bile salts to form MICELLES. AT the ileum of the small intestine, the FA and glycerol are absorbed and reformed along with cholesterol, free fatty acids, and phospholipids and coated with a protein to form a lipoprotein called a CHYLOMICRON. Chylomicrons are absorbed in the lactaeal and transported in the lymphatic system and emptied in to the circulatory system (superior vena cava).

Enyzmes in the capillary system hydrolyze the chylomicrons and release fatty acids and glycerol which are absorbed by the cells.

Glycerol --> glycerol 3 phosphate --> pyruvic acid --> Krebs

FA --> mitochondria and undergo BETA OXIDATION to form :

2 Acetyl CoA, that will combine with oxaloacetic acid to form citric acid to start the Krebs cycle

If FA/glycerol not needed, then recombined to neutral fat and stored as fat, by a process called lipogenesis.

To retreive fat :: lipolysis, and cause the breakdown of fat intoFA and glycerol.

Transport of FA to other tissues involves binding to a protein carrier.

The FA + protein carrier is called a free fatty acid.

Fats are used when CH2O levels are decreased and depends on hormonal effects of GH,TH, Epi/Norepi, Insulin, and glucocorticoids (GCC).

In the liver, FA will be degraded to AcetylCoA, and if not used in the Krebs cycle with oxaloacetic acid, then the 2 AcetylCoA will combine to form KETONE BODIES ::

Acetoacetic acid, which can then form two more ketone bodies --> acetone and betahydroxybutyric acid in a process called ketogenesis.

If ketone bodies accumulate will cause KETOSIS and drop the pH and create a metabolic acidosis

If CH2O excess, will first be stored as glycogen, then as triglycerides.

Fatty acid synthesis from CH2O important because :

Synthesis will not occur if insulin levels are decreased, because of decreased glucose entry into fat and liver.

PHOSPHOLIPIDS :: formed by all cells, but primarily liver

fxn : (see beginning section for list)

CHOLESTEROL :: source --> in diet , and liver synthesis, will always have a basal amount of cholesterol from the liver.

Fxn : (see list at beginning of section)

Increased ingestion will decrease liver synthesis

High saturated fats will stimulate liver synthesis

because Incr conc of fats --> incr acetylCoA --> cholesterol

Unsaturated fats will decrease the concentration of cholesterol and enhance excretion of cholesterol

Decreased insulin and decreased TH (thyroid hormone) will increase the concentration of cholesterol

Transport of cholesterol involves lipoproteins. Most lipoproteins are formed in the liver ::

Initial synthesis begins with very low density lipoproteins (VLDL) and have a high concentration of triglycerides (vs. cholesterol)

VLDL are metabolized and the triglycerides are removed to create a low density lipoprotein (LDL) that is high in cholesterol and phospholipids.

LDL are the bad cholesterol, since these lipoproteins are transporting cholesterol to the tissues for deposit.

The liver also makes high density lipoproteins (HDL) that are rich in phospholipids.

These (healthy) HDL will transport cholesterol from the tissue to the liver for excretion in the bile. HDL are the "GOOD" cholesterol (its good that we can get rid of it)

So what about chylomicrons, we said they were lipoproteins too, they are very very low density lipoproteins:: VVLDL.

Fat deposits :: storage as triglycerides in

adipose --> dynamic liquid state, turned over, no old

liver --> controlled by rate of lipids used for E.

PROTEINS :: complete (all amino acids present to meet req)

incomplete (some amino acids missing)

ALL amino acids must be present and available for protein synthesis to occur

Function --> linear for structure (collagen, keratin)

globular for enzymes, transport, muscle

3 major types ::

Albumin for colloid osmotic pressure, transport

Globulin for immune system, enzymes

Fibrinogen for coagulation

Structure : chemistry sites involve an acidic group (COOH) and an amine group (NH2) joined by peptide bonds

R group will vary and create 20 different AA

AA are at an equilbrium between plasma and cytoplasm of cell

Excess AA can be used for other products --> E or converted to fat or glycogen

Essential AA :: 10 are essential and required in the diet, while the other 10 can be synthesized in the liver

This synthesis of nonessential AA depends on the precursor formation of alpha keto acids

In synthesis :: in the liver will involve several steps

1. NH2 is removed from AA to form keto acid

2. This amino radical is transferred to a Krebs cycle keto acid (alpha keto acid) to form an AA (glutamic acid).

This process is called --> TRANSAMINATION.

3. Keto acid production from DEAMINATION (step 1)

can be used in the following ways ::

VITAMINS ::

source in diet, colon bacteria for B & K

stored in all cells, some vitamins primarily in the liver (A, D)

Fat soluble --> ADEK, absorbed in micelles

H2O soluble --> B, C diffusion

Toxicities :: hypervitaminosis (usually fat sol)

Deficiencies :: hypovitaminosis (usually H2O sol)

Vitamin A : carotenoid pigment that will be changed to Vit A

further changed for visual pigments (retinal)

a decrease will cause keritinization of epithelial cells

Thiamin (B1) : function in metabolic system, need for final metabolism of CH2O and AA decrease the affect CNS and heart

Niacin : coenzyme Hydrogen acceptors (NAD) decrease will decrease oxidative delivery of E

Riboflavin (B2) : coenzyme Hydrogen acceptor (FAD), decrease will decrease oxidative delivery of Energy (E)

Vit B12 (Cobalamin) : H+ acceptor, necessary for genetic replication

Folic Acid : synthesis of purine and thymine (DNA formation) required for gene replication promote growth and RBC maturation

Pyridoxine (B6) : coenzyme for AA/protein metabolism and transamination, Involved in AA transport across cell membrane

Pantothenic Acid (B5): incorporated into coenzyme A (CoA), involved in CH2O/fat metabolism

Ascorbic Acid (Vit C) : activating enzyme involved with collagen formation decrease affect bone, teeth, cartilage and affect wound healing

Vit D : increase Ca++ absorption from GI track and promote active transport through ileum

Vit E : prevent oxidation of unsaturated fatty acids; helps in membrane structure

Vit K : necessary for some blood clotting factors, synthesis by colon bacteria, found in diet

YOU NEED TO KNOW

3 Fat soluble vitamins and what they do, and

2 water soluble vitamins and what they do

for any test questions you might see in the future. Your choice

Water :: Balance between input and output

Input --> foods, liquids, metabolism

Output --> urine, feces, evaporation (skin, resp)

Requirements will vary according to environment and metabolic activity.

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Summary of LIVER METABOLIC FUNCTIONS ::

1. CH2O :: stores, converts

2. FAT :: stores, lipoproteins, synthesis of cholesterol, beta oxidation of fats --> ketone bodies

3. Protein : deamination, transamination

urea formation

plasma protein synthesis

4. MISC :: storage of Vit A, D, minerals, Fe+++ (iron)

drug metabolism : synthesis and activation

heme conversion to bilirubin

ENERGY USAGE will include two processes

1. ABSORPTIVE STATE :: nutrients absorbed from gi track that can be used for energy

a. CH2O --> monsacch B> liver --> glucose

3. GH, T4, Gonadal hormones

ENERGY BALANCE :: fuel burned consumes O2, liberates Heat

Total E intake = total energy output

Energy output involves :: heat, work and energy stored

Regulation of food intake :

1. nutrient signals --> plasma concentrations of glucose, AA and Fatty Acids

2. Hormones --> Insulin/Glucagon/ Epi/CCK

3. Body temp (incr temp, decreased appetite)

4. Psychological

METABOLISM :: all chemical reactions in the body

Metabolic rate --> rate of heat liberated during chemical reaction

Energy :: ATP used for

1. synthesis of ::