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1st Stage: Stage of Hydrolysis to Simpler Units
Sqadia video is the demonstration of Integration of Metabolism of Carbohydrates, Lipids and Proteins. The metabolic processes involving three major food nutrients (carbs, proteins, lipids) and their interrelationship can be broadly divided into three stages i.e. 1st stage: Stage of hydrolysis to simpler units, 2nd stage: Preparatory stage, 3rd stage: Oxidative stage–Aerobic final (TCA Cycle). In 1st stage, Complex polysaccharides, starch/glycogen are broken down to glucose, disaccharides are hydrolyzed to monosaccharides in GI tract, and lipids, triacylglycerol (TG) is hydrolysed to form FFA and glycerol, and Proteins are hydrolysed by proteolytic enzymes to amino acids. There is no storage of energy at this stage as it is dissipated away as heat.
2nd Stage: Preparatory Stage
In the Preparatory stage, the monosaccharide glucose runs through the glycolytic reactions to produce the 3-C keto acid pyruvic acid (PA) in the cytosol which in turn is transported to mitochondrion where it undergoes oxidative decarboxylation to produce 2-C compound “acetyl-CoA” (“active” acetate). The glycerol of fat, either goes into formation of glucose (gluconeogenesis) or by entering the same glycolytic pathway through the triose-P, forms PA and then finally 2-C compound “acetyl-CoA”. The fatty acids undergo principally β-oxidation and form several molecules of “acetyl-CoA”. The amino acids are deaminated and transaminated first and the C-skeleton is metabolized differently from amino acid to amino acid. Glycine, Alanine, Serine, Cystine and threonine when catabolized form pyruvic acid (PA) and is finally converted to ‘Acetyl CoA’ while Glutamic acid, Histidine, Proline and OH-proline, Arginine and Ornithine produces α-ketoglutaric acid. Leucine, Phenyl alanine, Tyrosine and Isoleucine yield acetate or acetoacetate, the latter can be converted to “acetyl-coA”.
3rd Stage: Oxidative Stage-Aerobic Final (TCA Cycle)
In presence of oxygen, acetyl-CoA is oxidized to CO₂ and H₂O by common final pathway TCA cycle. The carbohydrates, lipids and proteins all form acetate or some other intermediates like oxaloacetate (OAA), α-ketoglutarate, succinyl-CoA, or fumarate, which are all intermediates of TCA cycle. After entry into the TCA cycle at any site, two of carbons of “citrate” constituting an acetate moiety are oxidized finally to CO₂ and H₂O and the energy of oxidation by the electron transport chain is captured as energy-rich PO4– ATP mostly.
Interconversion Between the Three Principal Components
Carbohydrates can form lipids through formation of α-glycero-P from glycerol or di-hydroxy acetone-P (from glycolysis) which is necessary for Triacyl glycerol (TG) and FA from acetyl-CoA-extramitochondrial de novo synthesis. Carbohydrates can form non-essential amino acids through amination of α-ketoacids, viz. pyruvic acid (PA), oxaloacetic acid (OAA) and α-ketoglutarate to form amino acids alanine, aspartate and glutamate respectively. Fatty acids can be converted to some amino acids by forming the dicarboxylic acids like malic acid, oxalo-acetic acids and α-ketoglutarate. Fatty acid carbon may be incorporated into carbohydrates by the acetate running through TCA cycle. There is no net gain in carbohydrates, since two carbons, equivalent of acetate are oxidized in the cycle. Acetate can form glucose by running through the glyoxylate cycle. Acetone, one of the ketone bodies may be glucogenic. Acetone can be converted to acetol-P which in turn can produce propanediol-P.
Formation of Carbohydrates and Lipids from Amino-Acids
Proteins can form both carbohydrates and lipids through the glucogenic and ketogenic amino acids. The ratio of ATP/AMP of the cells/or tissues seems to decide the extent of its aerobic metabolism. If the ratio is high (low AMP or ADP level), this will have certain inhibitory effects of certain enzymes of glycolytic-TCA cycle. A high level of ATP and low level of AMP will inhibit the enzyme phosphofructokinase of glycolytic pathway and thereby inhibit glycolysis. As a result, there is accumulation of hexose-P which interacts with UTP to form UDP-G and proceeds to increased glycogen synthesis. The converse happens with low ATP and high AMP levels. Increased ATP/ADP ratio will stimulate PDH-kinase which in turn converts dephosphorylated active PDH (pyruvate dehydrogenase complex) to ‘inactive’ phosphorylated PDH inhibiting the oxidative decarboxylation of pyruvic acid (PA). High ATP/AMP ratio also lowers the activity of the enzymes Isocitrate dehydrogenase (ICD) of TCA cycle resulting in accumulation of citrate. Increased citric acid levels stimulate the enzyme acetyl-CoA carboxylase. Increased activity of acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA, the first step in extramitochondrial de novo FA synthesis. The reverse set of conditions operates when the ATP/ AMP ratio is low.