Metabolism of Nutrients II (Lipids & Proteins) PDF

Metabolism of nutrients Konstantinos Ekmektzoglou MD, PhD, FEBGH Assistant Professor School of Medicine European University Cyprus October 2024 Carbohydrates Lipids Proteins Carbohydrates Lipids Proteins Lipids include Neutral fat, also known as triglyce...

Metabolism of nutrients Konstantinos Ekmektzoglou MD, PhD, FEBGH Assistant Professor School of Medicine European University Cyprus October 2024 Carbohydrates Lipids Proteins Carbohydrates Lipids Proteins Lipids include Neutral fat, also known as triglycerides Phospholipids Cholesterol A few others of less importance Chemically the basic lipid moiety of triglycerides and phospholipids is fatty acids, which are long- chain hydrocarbon organic acids IMPORTANT – WHY? Triglycerides provide energy for the different metabolic processes (like carbohydrates) Cholesterol, phospholipids, and small amounts of triglycerides form the membranes of all cells of the body and perform other cellular functions three long-chain fatty acid molecules bound with one molecule of glycerol The three fatty acids most commonly present in the triglycerides of the human body are stearic acid oleic acid palmitic acid  most triglycerides are split into monoglycerides and fatty acids and are resynthesized into new molecules of triglycerides that enter the lymph as TRANSPORT almost all theOF fats TRIGLYCERIDES in the diet, AND OTHER LIPIDS FROM THE GI minute, dispersed droplets called (except a few short-chain fatty BY LYMPH—THE CHYLOMICRONS acids) are absorbed from the intestines chylomicrons into the intestinal lymph Chylomicron Triglycerides Are Hydrolyzed by Lipoprotein Lipase releasing fatty acids and glycerol Once inside these cells, the fatty acids can be used for fuel or again synthesized into triglycerides, with new glycerol being supplied by the metabolic processes of the storage cells  Free Fatty Acids When fat that has been stored in the adipose tissue is to be used elsewhere in the body to provide energy, it must first be transported from the adipose tissue to the other tissue It is transported mainly in the form of FFA (or non esterified fatty acids) This transport is achieved by hydrolysis of the triglycerides back into fatty acids and glycerol INTERESTINGLY ENOUGH FFA concentration in plasma is SMALL HOWEVER, BECAUSE the minute amount of FFA in the blood, its rate of “turnover” is extremely rapid: half the plasma fatty acid is replaced by new fatty acid every 2 to 3 minutes. THEREFORE, ALL normal energy requirements of the body can be provided by the oxidation of transported free fatty acids, without using any carbohydrates or proteins for energy Lipoproteins In the postabsorptive state, after all the chylomicrons have been removed from the blood > 95% of all lipids in the plasma are in the form of lipoprotein containing Triglycerides Cholesterol Phospholipids Protein TYPES of Lipoproteins Chylomicrons (very large lipoproteins) + very low density lipoproteins (VLDLs) high concentrations of triglycerides and moderate concentrations of both cholesterol and phospholipids intermediate-density lipoproteins (IDLs) VLDLs from which a share of the triglycerides has been removed, so the concentrations of cholesterol and phospholipids are increased Low density lipoproteins (LDLs) derived from IDLs by the removal of almost all the triglycerides, leaving an especially high concentration of cholesterol and a moderately high concentration of phospholipids High density lipoproteins (HDLs) contain a high concentration of protein (about 50 percent) but much smaller concentrations of cholesterol and phospholipids  Formed where? + small quantities of HDLs are synthesized in the intestinal epithelium during the absorption of fatty acids from the intestines Function? Transport their lipid components in the blood VLDLs transport triglycerides synthesized in the liver mainly to the adipose tissue other lipoproteins are especially important in the different stages of phospholipid and cholesterol transport from the liver to the peripheral tissues or from the periphery back to the liver LIVER in LIPID METABOLISM The principal functions of the liver in lipid metabolism degrade fatty acids into small compounds that can be used for energy synthesize triglycerides, mainly from carbohydrates, but to a lesser extent from proteins as well synthesize other lipids from fatty acids, especially cholesterol and phospholipids Use of Triglycerides for Energy: Formation of ATP enters the Triglycerides Hydrolysis Fatty acids + glycerol glycolytic pathway for BLOOD glucose breakdown Enter mitochondria for oxidized to give oxidation energy to tissues REMEMBER THE BRAIN USES GLC!!!!! Fatty acids inside mitochondria KREBS CYCLE COMPARED TO GLC HOW MUCH ENERGY IS PRODUCED???? 38 ATP molecules formed for each glc molecule 146 ATP molecules of ATP for each molecule of stearic acid  Formation of Acetoacetic Acid in the Liver and Its Transport in the Blood A large share of the initial degradation of fatty acids occurs in the liver However, the liver uses only a small proportion of the fatty acids for its own intrinsic metabolic processes Acetyl CoA for Krebs cycle Peripheral tissues  WHEN? BUT BE CAREFUL!!!! WHEN NO IF plasma levels of CARBOHYDRATES ARE METABOLISED acetoacetic acid β-hydroxybutyric acid Starvation, DM, fat diet acetone ARE INCREASED THEN KETOSIS CAN TRIGLYCERIDES BE FORMED BY CARBS? Whenever ⇑ carbohydrates used immediately for energy or stored in the form of glycogen ▼ the excess is rapidly converted into triglycerides and stored in adipose tissue WHERE? The triglycerides formed in the liver are transported mainly in VLDLs to the adipose tissue, where they are stored  HOW? 1. Conversion of Acetyl-CoA Into Fatty Acids 2. Combination of Fatty Acids With α-Glycerophosphate to Form Triglycerides WHY IT IS SO IMPORTANT TO MAKE AND STORE FAT? The ability of the different cells of the body to store carbohydrates in the form of glycogen is generally low Each gram of fat contains almost two and a half times the calories of energy contained by each gram of glycogen CAN TRIGLYCERIDES BE FORMED BY PROTEINS? YES – WE WILL DISCUSS THAT LATER WHAT HAPPENS IF I EAT TO MUCH CARBS TO FAT METABOLISM? Carbohydrates Are Preferred Over Fats for Energy FAT - When Excess Carbohydrates Are Available SPARING WHAT HAPPENS IF I EAT NO CARBS TO FAT METABOLISM? Fat is mobilized from adipose cells and FAT - used for energy in place of SPARING carbohydrates Hormonal Regulation of Fat Utilization  OK WITH TRIGLYCERIDES – BUT WHAT WITH PHOSHOLIPIDS AND CHOLESTEROL? Phospholipids Lecithins Cephalins Sphingomyelin 90% formed in liver lipid soluble transported in lipoproteins used throughout the body for various structural purposes, such as in cell membranes and intracellular membranes Cholesterol fat soluble capable of forming esters with fatty acids EXOGENOUS absorbed from the GI tract into the intestinal lymph ENDOGENOUS formed in the cells of the body Specific Uses of Cholesterol in the Body. forms cholic acid in the liver conjugated with other substances to form bile salts, which promote digestion and absorption of fats Control of Cholesterol Homeostasis  Factors That Affect Plasma Cholesterol Concentration— Feedback Control of Body Cholesterol ▲ of cholesterol ingested ► feedback control system to prevent an excessive ▲ in plasma cholesterol concentration A diet ▲ in saturated fat ▲ blood cholesterol concentration due to increase in increased fat deposition in the liver (▲ quantities of acetyl-CoA in the liver cells for the production of cholesterol) Ingestion of fat containing ▲ unsaturated fatty acids usually depresses the blood cholesterol concentration ` Lack of insulin or thyroid hormone Ingestion of fat containing ▲ the blood cholesterol concentration, whereas excess thyroid hormone ▼ the concentration Genetic disorders of cholesterol metabolism Carbohydrates Lipids Proteins The principal constituents of proteins are amino acids (AAs) Twenty of these AAs are present in the body proteins in significant quantities Each AA has an acidic group (–COOH) and a nitrogen atom attached to the molecule, usually represented by the amino group (–NH2). Peptide Linkages and Peptide Chains The AAs of proteins are aggregated into long chains by means of peptide linkage nitrogen of the amino radical of one amino acid bonds with the carbon of the carboxyl radical of the other amino acid  α-keto HOW ARE NON ESSENTIAL AAs formed FROM ESSENTIAL AAs? acid transamination amino radical is transferred to the α-keto acid, and the keto oxygen is transferred to the donor of the amino radical Transport and Storage of Amino Acids protein digestion and absorption in the GI tract gastrointestinal tract ► almost entirely AAs (only rarely are polypeptides or whole protein molecules absorbed from the digestive tract into the blood) ΑΑs are relatively strong acids ► they exist in the blood principally in the ionized state, as a result of the removal of one H atom from the NH2 radical Active Transport of Amino Acids Into the Cells Molecules of Aas are much too large to diffuse readily through the pores of the cell membranes Therefore, significant quantities of Aas can move either inward or outward through the membranes only by facilitated transport or active transport using carrier mechanisms DO NOT FORGET AAs can be reabsorbed in the kidneys by secondary active transport What happens when AAs enter the cell? Molecules of AAs are much too large to diffuse readily through the pores of the cell membranes ► AΑs can move either inward or outward through the membranes only by facilitated transport or active transport using carrier mechanisms After entry into tissue cells, amino acids combine with one another by peptide linkages, under the direction of the cell’s messenger RNA and ribosomal system, to form cellular proteins intracellular proteins can be rapidly decomposed again into AAs due to intracellular lysosomal digestive enzymes AND TRANSPORTED back out of the cell into the blood. Reversible Equilibrium Between Plasma and Tissue Proteins Albumin Globulin Fibrinogen Proteins and energy Where? DEAMINATION REVERSE OF TRANSAMINATION Deamination Removal of Amino Groups From AAs What happens after deamination? OXIDATION OF KETO-ACIDS Proteins in the body are constantly synthesized and degraded, partially draining and refilling the cellular amino acid pools. In a well fed, healthy human adult, approximately 300 - 600 grams of new protein are synthesized each day. Growth factors, hormones, including insulin, and cytokines stimulate protein synthesis. Hormonal Regulation of Protein Metabolism