NEET MDS Lessons
Biochemistry
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
Clinical significance
Primary hyperparathyroidism is due to autonomous, abnormal hypersecretion of PTH in the parathyroid gland
Secondary hyperparathyroidism is an appropriately high PTH level seen as a physiological response to hypocalcemia.
A low level of PTH in the blood is known as hypoparathyroidism and is most commonly due to damage to or removal of parathyroid glands during thyroid surgery.
MAGNESIUM
The normal serum level of Magnesium is 1.8 to 2.2. mg/dl.
Functions of Magnesium
(a) Irritability of neuromuscular tissues is lowered by Magnesium
(b) Magnesium deficiency leads to decrease in Insulin dependent uptake of glucose
(c) Magnesium supplementation improves glucose tolerance
Causes such as liver cirrhosis, protein calorie malnutrition and hypo para thyroidism leads to hypomagnesemia
The main causes of hypermagnesemia includes renal failure, hyper para thyroidism, rickets, oxalate poisoning and multiple myeloma.
Gluconeogenesis
It is the process by which Glucose or glycogen is formed from non carbohydrate substances.
Gluconeogenesis occurs mainly in liver.
Gluconeogenesis inputs:
The source of pyruvate and oxaloacetate for gluconeogenesis during fasting or carbohydrate starvation is mainly amino acid catabolism. Some amino acids are catabolized to pyruvate, oxaloacetate, Muscle proteins may break down to supply amino acids. These are transported to liver where they are deaminated and converted to gluconeogenesis inputs.
Glycerol, derived from hydrolysis of triacylglycerols in fat cells, is also a significant input to gluconeogenesis
Glycolysis & Gluconeogenesis pathways are both spontaneous If both pathways were simultaneously active within a cell it would constitute a "futile cycle" that would waste energy
Glycolysis yields 2~P bonds of ATP.
Gluconeogenesis expends 6~P bonds of ATP and GTP.
A futile cycle consisting of both pathways would waste 4 P.bonds per cycle.To prevent this waste, Glycolysis and Gluconeogenesis pathways are reciprocally regulated.
PROPERTIES OF TRIACYLGTYCEROLS
1. Hydrolysis : Triacylglycerols undergo stepwise enzymatic hydrolysis to finally liberate free fatty acids and glycerol.
The process of hydrolysis, catalysed by lipases is important for digestion of fat in the gastrointestinal tract and fat mobilization from the adipose tissues.
2. Saponification : The hydrolysis of triacylglycerols by alkali to produce glycerol and soaps is known as saponification.
3.Rancidity: Rancidity is the term used to represent the deterioration of fats and oils resulting in an unpleasant taste. Fats containing unsaturated fatty acids are more susceptible to rancidity.
Hydrolytic rancidity occurs due to partial hydrolysis of triacylglycerols by bacterial enzymes.
Oxidative rancidity is due to oxidation of unsaturated fatty acids.
This results in the formation of unpleasant products such as dicarboxylic acids, aldehydes, ketones etc.
Antioxidants : The substances which can prevent the occurrence of oxidative rancidity are known as antioxidants.
Trace amounts of antioxidants such as tocopherols (vitamin E), hydroquinone, gallic acid and c,-naphthol are added to the commercial preparations of fats and oils to prevent rancidity. Propylgallate, butylatedhydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are the antioxidants used in food preservation.
Lipid peroxidation in vivo: In the living cells, lipids undergo oxidation to produce peroxides and free radicals which can damage the tissue. .
The free radicals are believed to cause inflammatory diseases, ageing, cancer , atherosclerosis etc
Iodine number : lt is defined as the grams (number) of iodine absorbed by 100 g of fat or oil. lodine number is useful to know the relative
unsaturation of fats, and is directly proportional to the content of unsaturated fatty acids
Determination of iodine number will help to know the degree of adulteration of a given oil
Saponification number : lt is defined as the mg (number) of KOH required to hydrolyse (saponify) one gram of fat or oiL
Reichert-Meissl (RM) number: lt is defined as the number of ml 0.1 N KOH required to completely neutralize the soluble volatile fatty acids distilled from 5 g fat. RM number is useful in testing the purity of butter since it contains a good concentration of volatile fatty acids (butyric acid, caproic acid and caprylic acid).
Acid number : lt is defined as the number of mg of KOH required to completely neutralize free fatty acids present in one gram fat or oil. In normal circumstances, refined oils should be free from any free fatty acids.
Glycogenolysis
Breakdown of glycogen to glucose is called glycogenolysis. The Breakdown of glycogen takes place in liver and muscle. In Liver , the end product of glycodgen breakdown is glucose where as in muscles the end product is Lactic acid Under the combined action of Phosphorylase (breaks only –α-(1,4) linkage )and Debranching enzymes (breaks only α-(1,6) linkage )glycogen is broken down to glucose.
These amino acids have aromatic side chains, which contribute to protein structure, UV absorbance, and biochemical signaling.
1. Phenylalanine (Phe, F)
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Structure: Contains a benzyl side chain (a phenyl group attached to a CH₂).
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Properties: Non-polar, hydrophobic.
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Function: Precursor to tyrosine, dopamine, norepinephrine, and epinephrine.
2. Tyrosine (Tyr, Y)
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Structure: Similar to phenylalanine but with a hydroxyl group (-OH) on the aromatic ring.
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Properties: Polar, can participate in hydrogen bonding.
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Function: Precursor to catecholamines and thyroid hormones; involved in signal transduction via phosphorylation.
3. Tryptophan (Trp, W)
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Structure: Contains an indole ring (a fused double ring with nitrogen).
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Properties: Slightly polar, bulky.
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Function: Precursor to serotonin, melatonin, and niacin; absorbs UV light strongly at 280 nm.
4. Histidine (His, H) (sometimes included due to its aromatic-like imidazole ring)
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Structure: Has an imidazole ring (five-membered ring with two nitrogen atoms).
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Properties: Polar, positively charged at physiological pH.
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Function: Key role in enzyme active sites; acts as a proton donor/acceptor.
Bonus Insight: UV Absorbance
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Tryptophan and Tyrosine absorb UV light at ~280 nm, which is useful for measuring protein concentration.
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Phenylalanine absorbs weakly at ~260 nm.