Functions of  lipids

1. They are the concentrated fuel reserve of the body  (triacylglycerols).

2. Lipids are the constituents of membrane structure and regulate the membrane permeability (phospholipids  and cholesterol).

3. They serve as a source of fat soluble vitamins (A, D, E and K).

4. Lipids are important as cellular metabolic regulators (steroid  hormones and prostaglandins).

5. Lipids protect the internal organs, serve as insulating materials and give shape and smooth appearance to the body.

BIOLOGICAL BUFFER SYSTEMS 

Cells and organisms maintain a specific and constant cytosolic pH, keeping biomolecules in their optimal ionic state, usually near pH 7. In multicelled organisms, the pH of the extracellular fluids (blood, for example) is also tightly regulated. Constancy of pH is achieved primarily by biological buffers : mixtures of weak acids and their conjugate bases 

Body fluids and their principal buffers

Body fluids                     Principal buffers

Extracellular fluids        {Biocarbonate buffer Protein buffer } 

Intracellular fluids         {Phosphate buffer, Protein }

Erythrocytes                 {Hemoglobin buffer}

The Phosphate Buffer System

This system, which acts in the cytoplasm of all cells, consists of H₂PO₄^–  as proton donor and HPO₄ ^2– as proton acceptor :

H₂PO₄^–  = H⁺ + H₂PO₄^–

The phosphate buffer system works exactly like the acetate buffer system, except for the pH range in which it functions. The phosphate buffer system is maximally effective at a pH close to its pKa of 6.86 and thus tends to resist pH changes in the range between 6.4 and 7.4. It is, therefore, effective in providing buffering power in intracellular fluids.

Buffers           

• Biological systems use buffers to maintain pH.

• Definition: A buffer is a solution that resists a significant change in pH upon addition of an acid or a base.

• Chemically: A buffer is a mixture of a weak acid and its conjugate base

• Example: Bicarbonate buffer is a mixture of carbonic acid (the weak acid) and the bicarbonate ion (the conjugate base): H₂CO₃ + HCO₃ ^–

• All OH- or H+ ions added to a buffer are consumed and the overall [H+ ] or pH is not altered

H₂CO₃ + HCO₃ ^- + H⁺ <- -> 2H₂CO₃

H₂CO₃ + HCO₃ -  +  OH^-  <- -> 2HCO₃  ^- + H₂O

• For any weak acid / conjugate base pair, the buffering range is its pKa +1.

It should be noted that around the pK_a the pH of a solution does not change appreciably even when large amounts of acid or base are added. This phenomenon is known as buffering. In most biochemical studies it is important to perform experiments, that will consume H⁺ or OH^- equivalents, in a solution of a buffering agent that has a pK_a near the pH optimum for the experiment.

Most biologic fluids are buffered near neutrality. A buffer resist a pH change and consists of a conjugate acid/base pair.

Important Physiological Buffers include carbonate (H₂CO₃/HCO₃^-),

Phosphate (H₂PO^-₄ /HPO^2-₄) and various protiens

Niacin: Vitamin B3, Nicotinamide, Nicotinic Acid Niacin, or vitamin B3,

 is involved in energy production, normal enzyme function, digestion, promoting normal appetite, healthy skin, and nerves.

RDA Males: 16 mg/day; Females: 14 mg/day

Niacin Deficiency : Pellagra is the disease state that occurs as a result of severe niacin deficiency. Symptoms include cramps, nausea, mental confusion, and skin problems.

Step 1.  Acyl-CoA Dehydrogenase catalyzes oxidation of the fatty acid moiety of acyl-CoA, to produce a double bond between carbon atoms 2 and 3.

There are different Acyl-CoA Dehydrogenases for short (4-6 C), medium (6-10 C), long and very long (12-18 C) chain fatty acids. Very Long Chain Acyl-CoA Dehydrogenase is bound to the inner mitochondrial membrane. The others are soluble enzymes located in the mitochondrial matrix.

FAD is the prosthetic group that functions as electron acceptor for Acyl-CoA Dehydrogenase. 

A glutamate side-chain carboxyl extracts a proton from the a-carbon of the substrate, facilitating transfer of 2 e^- with H⁺ (a hydride) from the b position to FAD. The reduced FAD accepts a second H⁺, yielding FADH₂

The carbonyl oxygen of the thioester substrate is hydrogen bonded to the 2'-OH of the ribityl moiety of FAD, giving this part of FAD a role in positioning the substrate and increasing acidity of the substrate a-proton

The reactive glutamate and FAD are on opposite sides of the substrate at the active site. Thus the reaction is stereospecific, yielding a trans double bond in enoyl-CoA.

FADH₂ of Acyl CoA Dehydrogenase is reoxidized by transfer of 2 electrons to an Electron Transfer Flavoprotein (ETF), which in turn passes the electrons to coenzyme Q of the respiratory chain.

Step 2. Enoyl-CoA Hydratase catalyzes stereospecific hydration of the trans double bond produced in the 1st step of the pathway, yielding L-hydroxyacyl-Coenzyme A

Step 3. Hydroxyacyl-CoA Dehydrogenase catalyzes oxidation of the  hydroxyl in the b position (C3) to a ketone. NAD⁺ is the electron acceptor.

Step 4. b-Ketothiolase (b-Ketoacyl-CoA Thiolase) catalyzes thiolytic cleavage.

A cysteine S attacks the b-keto C. Acetyl-CoA is released, leaving the fatty acyl moiety in thioester linkage to the cysteine thiol. The thiol of HSCoA displaces the cysteine thiol, yielding fatty acyl-CoA (2 C shorter).

A membrane-bound trifunctional protein complex with two subunit types expresses the enzyme activities for steps 2-4 of the b-oxidation pathway for long chain fatty acids. Equivalent enzymes for shorter chain fatty acids are soluble proteins of the mitochondrial matrix.

Summary of one round of the b-oxidation pathway:

fatty acyl-CoA + FAD + NAD⁺ + HS-CoA → 
            fatty acyl-CoA (2 C shorter) + FADH₂ + NADH + H⁺ + acetyl-CoA

The b-oxidation pathway is cyclic. The product, 2 carbons shorter, is the input to another round of the pathway. If, as is usually the case, the fatty acid contains an even number of C atoms, in the final reaction cycle butyryl-CoA is converted to 2 copies of acetyl-CoA

ATP production:

• FADH₂ of Acyl CoA Dehydrogenase is reoxidized by transfer of 2 e^- via ETF to coenzyme Q of the respiratory chain. H⁺ ejection from the mitochondrial matrix that accompanies transfer of 2 e^- from CoQ to oxygen, leads via chemiosmotic coupling to production of approximately 1.5 ATP. (Approx. 4 H⁺ enter the mitochondrial matrix per ATP synthesized.)
• NADH is reoxidized by transfer of 2 e^- to the respiratory chain complex I. Transfer of 2 e^- from complex I to oxygen yields approximately 2.5 ATP.
• Acetyl-CoA can enter Krebs cycle, where the acetate is oxidized to CO₂, yielding additional NADH, FADH₂, and ATP. 
• Fatty acid oxidation is a major source of cellular ATP

b-Oxidation of very long chain fatty acids also occurs within peroxisomes

FAD is electron acceptor for peroxisomal Acyl-CoA Oxidase, which catalyzes the first oxidative step of the pathway. The resulting FADH₂ is reoxidized in the peroxisome producing hydrogen peroxide FADH₂ + O₂ à FAD + H₂O₂

The peroxisomal enzyme Catalase degrades H₂O₂ by the reaction:
2 H₂O₂ → 2 H₂O + O₂
These reactions produce no ATP

Once fatty acids are reduced in length within the peroxisomes they may shift to the mitochondria to be catabolized all the way to CO₂. Carnitine is also involved in transfer of fatty acids into and out of peroxisomes