NEET MDS Lessons
Biochemistry
Pentose Phosphate Pathway (Hexose Monophosphate Shunt)
The pentose phosphate pathway is primarily an anabolic pathway that utilizes the 6 carbons of glucose to generate 5 carbon sugars and reducing equivalents. However, this pathway does oxidize glucose and under certain conditions can completely oxidize glucose to CO2 and water. The primary functions of this pathway are:
- To generate reducing equivalents, in the form of NADPH, for reductive biosynthesis reactions within cells.
- To provide the cell with ribose-5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids.
- Although not a significant function of the PPP, it can operate to metabolize dietary pentose sugars derived from the digestion of nucleic acids as well as to rearrange the carbon skeletons of dietary carbohydrates into glycolytic/gluconeogenic intermediates
Enzymes that function primarily in the reductive direction utilize the NADP+/NADPH cofactor pair as co-factors as opposed to oxidative enzymes that utilize the NAD+/NADH cofactor pair. The reactions of fatty acid biosynthesis and steroid biosynthesis utilize large amounts of NADPH. As a consequence, cells of the liver, adipose tissue, adrenal cortex, testis and lactating mammary gland have high levels of the PPP enzymes. In fact 30% of the oxidation of glucose in the liver occurs via the PPP. Additionally, erythrocytes utilize the reactions of the PPP to generate large amounts of NADPH used in the reduction of glutathione. The conversion of ribonucleotides to deoxyribonucleotides (through the action of ribonucleotide reductase) requires NADPH as the electron source, therefore, any rapidly proliferating cell needs large quantities of NADPH.
Regulation: Glucose-6-phosphate Dehydrogenase is the committed step of the Pentose Phosphate Pathway. This enzyme is regulated by availability of the substrate NADP+. As NADPH is utilized in reductive synthetic pathways, the increasing concentration of NADP+ stimulates the Pentose Phosphate Pathway, to replenish NADPH
The pH scale
An acidic solution is one in which [H+ ] > [OH- ]
•In an acidic solution, [H+ ] > 10-7 , pH < 7.
•A basic solution is when [OH- ] > [H+ ].
•In a basic solution, [OH- ] > 10-7 , pOH < 7, and pH >7.
• When the pH = 7, the solution is neutral.
•Physiological pH range is 6.5 to 8.0
LIPOPROTIENS
Lipoproteins Consist of a Nonpolar Core & a Single Surface Layer of Amphipathic Lipids
The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules .These are oriented so that their polar groups face outward to the aqueous medium. The protein moiety of a lipoprotein is known as an apolipoprotein or apoprotein,constituting nearly 70% of some HDL and as little as 1% of Chylomicons. Some apolipoproteins are integral and cannot be removed, whereas others can be freely transferred to other lipoproteins.
There re five types of lipoproteins, namely chylomicrons, very low density lipoproteins(VLDL) low density lipoproteins (LDL), high density Lipoproteins (HDL) and free fatty acid-albumin complexes.
Weak Acids and pKa
• The strength of an acid can be determined by its dissociation constant, Ka.
• Acids that do not dissociate significantly in water are weak acids.
• The dissociation of an acid is expressed by the following reaction: HA = H+ + A- and the dissociation constant Ka = [H+ ][A- ] / [HA]
• When Ka < 1, [HA] > [H+ ][A- ] and HA is not significantly dissociated. Thus, HA is a weak acid when ka < 1.
• The lesser the value of Ka, the weaker the acid.
• Similar to pH, the value of Ka can also be represented as pKa.
• pKa = -log Ka.
• The larger the pKa, the weaker the acid.
• pKa is a constant for each conjugate acid and its conjugate base pair.
• Most biological compounds are weak acids or weak bases.
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.
Folate: Folic Acid, Folacin Folate, also known as folic acid or folacin, aids in protein metabolism, promoting red blood cell formation, and lowering the risk for neural tube birth defects. Folate may also play a role in controlling homocysteine levels, thus reducing the risk for coronary heart disease.
RDA for folate is 400 mcg/day for adult males and females. Pregnancy will increase the RDA for folate to 600 mcg/day.
Folate Deficiency
Folate deficiency affects cell growth and protein production, which can lead to overall impaired growth. Deficiency symptoms also include anemia and diarrhea.
A folate deficiency in women who are pregnant or of child bearing age may result in the delivery of a baby with neural tube defects such as spina bifida.
During fasting or carbohydrate starvation, oxaloacetate is depleted in liver because it is used for gluconeogenesis. This impedes entry of acetyl-CoA into Krebs cycle. Acetyl-CoA then is converted in liver mitochondria to ketone bodies, acetoacetate and b-hydroxybutyrate.
Three enzymes are involved in synthesis of ketone bodies:
b-Ketothiolase. The final step of the b-oxidation pathway runs backwards, condensing 2 acetyl-CoA to produce acetoacetyl-CoA, with release of one CoA.
HMG-CoA Synthase catalyzes condensation of a third acetate moiety (from acetyl-CoA) with acetoacetyl-CoA to form hydroxymethylglutaryl-CoA (HMG-CoA).
HMG-CoA Lyase cleaves HMG-CoA to yield acetoacetate plus acetyl-CoA.
b-Hydroxybutyrate Dehydrogenase catalyzes inter-conversion of the ketone bodies acetoacetate and b-hydroxybutyrate.
Ketone bodies are transported in the blood to other tissue cells, where they are converted back to acetyl-CoA for catabolism in Krebs cycle