Badil Dass

Lecturer Lecturer

Karachi King’s College of Nursing

Metabolism

Badil Dass

Lecturer

�By the end of this presentation, you will be able to:

�Define metabolism, catabolism and anabolism.

�Define ATP and its relationship with catabolism and anabolism.

�Discuss gluconeogenesis,glycogenesis, glucogenolysis,transamination, deamination and ketosis.glucogenolysis,transamination, deamination and ketosis.

�Discuss the following metabolic pathways for carbohydrate, proteins and fats in terms of glycolysis, kreb’s

cycle and electron transport chain.

Metabolism

� The sum total of the chemical processes that occur in living organisms, resulting in growth, production of energy, elimination of waste material, etc.

� Anabolism- build up of complex molecules

� Catabolism- break down of complex molecules

Adenosine triphosphate� An important carrier of energy in cells in the body and

a compound that is important in the synthesis (the making) of RNA. Adenosine triphosphate (ATP) is a nucleotide (a building block of a nucleic acid such as RNA). The body produces ATP from food and then RNA). The body produces ATP from food and then ATP produces energy as needed by the body.

�

�Oxidation is the removal of electron from an atom or molecule, the result is decreases in potential energy of

atom or molecule.

�Most of biological oxidation reactions involve the loss of hydrogen atoms, they are called dehydrogenation reaction.hydrogen atoms, they are called dehydrogenation reaction.

�Example conversion of lactic acid into pyruvic acid.

�Reduction is the opposite of oxidation,it is the addition of electrons to a molecule.

�Example: conversion of pyruvic acid into lactic acid.�Example: conversion of pyruvic acid into lactic acid.

�Oxidation and reduction reactions are always coupled ;each time one substance and another is simultaneously

reduced.such paired reactions are called oxidation-reduction or redox reactions.

�Substrate-level phosphorylation

�Substrate transfers a phosphate group directly

�Requires enzymes

�Phosphocreatine + ADP Creatine + ATP�Phosphocreatine + ADP Creatine + ATP

�Oxidative phosphorylation

�Method by which most ATP formed

�Small carbon chains transfer hydrogens to transporter (NAD or FADH) which enters the

electron transport chain

�Primarily glucose

�Fructose and galactose enter the pathways at various points

�All cells can utilize glucose for energy production

�Glucose uptake from blood to cells usually mediated by insulin and transportersinsulin and transporters

�Liver is central site for carbohydrate metabolism

�Glucose uptake independent of insulin

�The only exporter of glucose

�Several cell types prefer glucose as energy source

�80-100 mg/dl is normal range of blood glucose in non-ruminant animals� Uses of glucose:� Uses of glucose:

�Energy source for cells

� Muscle glycogen

� Fat synthesis if in excess of needs

�Fed state

�Storage as glycogen

�Liver

�Skeletal muscle�Skeletal muscle

�Storage as lipids

�Adipose tissue

�Fasted state

�Metabolized for energy

�New glucose synthesized

High Blood Glucose

Insulin

Pancreas

Muscle Glycogen

Glucose absorbed

Adipose Cells

Glucose absorbed

Glucose absorbed

�Four major metabolic pathways:

�Immediate source of energy� Pentophosphate pathway� Pentophosphate pathway� Glycogen synthesis in liver/muscle� Precursor for triacylglycerol synthesis

�Energy status (ATP) of body regulates which pathway gets energy

�Same in ruminants and non-ruminants

�1st Priority: glycogen storage

�Stored in muscle and liver

�2nd Priority: provide energy

�Oxidized to ATP�Oxidized to ATP

�3rd Priority: stored as fat

�Only excess glucose

�Stored as triglycerides in adipose

�The body can store about 500 g(1.1 lb)of glycogen.

Glucose storage: Glycogenesis�If glucose is not needed immediately for ATP

production, it combines with many other molecules of glucose to form glycogen, a polysaccrides that is the only stored form the CHO polysaccrides that is the only stored form the CHO in our bodies.

�The harmone insuline stimulates the hepatocytes and skeletal muscle cells to carry out glycogenesis, the synthesis of glycogen.

�The body can store about 500g(about 1.1 lb) of glycogen, roughly 75% in skeletal muscle fibres and the rest in liver cells.

Contd.�During the glycogenesis, glucose is first

phosphorylated to glucose 6- phosphate by hexokinase.

�Glucose 6-phosphate is converted to glucose 1-�Glucose 6-phosphate is converted to glucose 1-phosphate, then to uridine diphosphate glucose and finally to glycogen.

Glucose release: Glucogenolysis�When body activities require ATP, glycogen stored in

hepatocytes is broken down into glucose and released into the blood to be transported to cells, where it will be catabolized by the processes of cellular respiration.be catabolized by the processes of cellular respiration.

�The process of splitting glycogen to glucose subunits is called glycogenolysis.

Protein MetabolismProtein Metabolism

During digestion, proteins are broken down into During digestion, proteins are broken down into

amino acids.amino acids.

Unlike CHO and TGL, which are stored.Unlike CHO and TGL, which are stored.

Proteins are not warehoused for future use. Proteins are not warehoused for future use. Proteins are not warehoused for future use. Proteins are not warehoused for future use.

Instead, amino acids are either oxidized to Instead, amino acids are either oxidized to

produce ATP or used to synthesized new proteins produce ATP or used to synthesized new proteins

for body repair and growth.for body repair and growth.

Excess dietary amino acids are not excreted in the Excess dietary amino acids are not excreted in the

urine and feces but instead are converted into urine and feces but instead are converted into

glucose (gluconeogenesis) or TGL (lipogenesis).glucose (gluconeogenesis) or TGL (lipogenesis).

The fate of proteins�The active transport of amino acids into body cells

is stimulated by insulinlike growth factors(IGFs) and insulin.

�Almost immediately after digestion, amino acids �Almost immediately after digestion, amino acids are reassembled into proteins.

�Many proteins function as enzymes; others are involved in transportation(hemoglobin) or serve as antibodies, clotting chemicals(fibrinogen), harmones (insulin) or contractile elementsin muscle fibers(actin or myosin).

��No storage facility for amino acidsNo storage facility for amino acids

��Amino acids incorporated into functional proteinsAmino acids incorporated into functional proteins

��Amino acids in blood and extracellular fluid represent Amino acids in blood and extracellular fluid represent

an ‘amino acid pool’an ‘amino acid pool’

��Amino acids move through this poolAmino acids move through this pool

��Average 60 kg womanAverage 60 kg woman

��10 kg protein10 kg protein

��170 g free amino acids in pool170 g free amino acids in pool

��Protein content of adult body remains remarkably Protein content of adult body remains remarkably constant.constant.

Protein constitutes 10Protein constitutes 10--15% of diet.15% of diet.Equivalent amount of amino acids must be lost each day.Equivalent amount of amino acids must be lost each day.Equivalent amount of amino acids must be lost each day.Equivalent amount of amino acids must be lost each day.

Proteins synthesis in all body cells and is stimulated by Proteins synthesis in all body cells and is stimulated by insulin,thyroid harmones and insulinlike growth factorsinsulin,thyroid harmones and insulinlike growth factors

Metabolism of amino acids differs, but 3 common reactions:Metabolism of amino acids differs, but 3 common reactions:

��TransaminationTransamination��TransaminationTransamination

��DeaminationDeamination

��Formation of ureaFormation of urea

��Amino group removed from one amino acid and transferred Amino group removed from one amino acid and transferred to anotherto another

��Catalysed by aminotransferase enzymesCatalysed by aminotransferase enzymes

��Nearly all transaminations transfer amino group to Nearly all transaminations transfer amino group to αα--ketoglutarateketoglutarateketoglutarateketoglutarate

��Forms new ketoacid and glutamate (amino acid)Forms new ketoacid and glutamate (amino acid)

��Amino group (and H) removedAmino group (and H) removed

��Forms ammonia (NHForms ammonia (NH33))

��Carbon skeleton left can beCarbon skeleton left can be

��Oxidised Oxidised

��used for gluconeogenesisused for gluconeogenesis

��converted to fatty acidconverted to fatty acid

��18 amino acids glucogenic/ketogenic18 amino acids glucogenic/ketogenic

��Leucine and lysine purely ketogenicLeucine and lysine purely ketogenic

��Ammonia is toxicAmmonia is toxic

��Readily ionises to ammonium ion NHReadily ionises to ammonium ion NH44++

��NHNH44+ + converted to urea in liver (urea cycle)converted to urea in liver (urea cycle)

Urea contains 2 x NHUrea contains 2 x NH��Urea contains 2 x NHUrea contains 2 x NH22

��One from NHOne from NH44++

��One from aspartate One from aspartate

��Urea excreted in urineUrea excreted in urine

Lipid MetabolismLipid Metabolism

�Fats are not water soluble

�Made into bile salts that are

�Absorbed as micelles in small intestines.

�The lipid and protein combination is lipoproteins

�There are four major classes of lipoproteins:�There are four major classes of lipoproteins:

�Chylomicrons

�Very low density lipoproteins(VLDLs)

�Low density lipoproteinsI(LDL)

�High density lipoproteins(HDL)

Chylomicron Carriers

Proteins that carry fatsProteins that carry fats

stored in adipose tissue

It forms in mucosal epithelial cells of the small

intestine, transport dietry (ingested)

lipids to adipose tissue for storage.

They contain about 1-2% proteins,85%TGL,7%

phospholipids and 6-7% cholesterol.

�Which form in hepatocytes, contain mainly endogenous lipids (made in the body).

�VLDLs contain about 10% proteins, 50% TGL, 20 % �VLDLs contain about 10% proteins, 50% TGL, 20 % phospholipids and 20% cholesterol.

�Contains 25% proteins, 5% TGL, 20% phospholipids and 50% cholesterol.

�They carry about 75% of the total cholesterol in blood and deliver it to cells throughout the body for use in repair of cell deliver it to cells throughout the body for use in repair of cell membranes and synthesis of steroid harmones and bile salts.

�Which contain 40-45% proteins,5-10% triglycerides ,30% phospholipids ,and 20% cholesterol, remove excess

cholesterol from body cells and the blood and transport it to the liver for elimination.Because HDLs prevent accumulation the liver for elimination.Because HDLs prevent accumulation

of cholesterol in the blood,a high HDL level is associated with decreased risk of coronary artery disease.for this reason,HDL-

cholesterol is known as “good cholesterol”

�In order for muscle, liver and adipose tissue to oxidize the fatty acids derived from triglycerides to produce ATP, the

triglycerides must first be split into glycerol and fatty acids, a process called lipolysis.

�Lipolysis is catalyzed by enzyme called lipases.

�Epinephrine and norepinephrine enhance TGL breakdown into fatty acids and glycerol.

�As a part of normal fatty acid catabolism,

hepatocytes can take two acetyl molecules at a

time and condense them to form acetoacetic acid.

This reaction liberates the bulky CoA portion, which

cannot diffuse out of cells

some acetoacetic acid is converted into beta-

hydroxybutyric acid and acetone.

The formation of these three substances collectively

known as ketone bodies, is called ketogenesis.

�Liver cells and adipose cells can synthesize lipids from glucose or amino acids through lipogenesis, which is

stimulated by insulin.

�Lipogenesis occurs when individuals consume more calories than are needed to satisfy their ATP needs.

�The chemical reactions of living systems depend on the effecient transfer of manageable amounts of energy from

one molecule to another.

�The molecule that most often performs this task is ATP.

�A typical cell cell has about a billion molecules of ATP. �A typical cell cell has about a billion molecules of ATP.

�Molecule of ATP consists of an adenine molecule ,a ribose molecule,and three phosphate groups bonded to one

another.

Cont.�when the terminal phosphate group is split off

ATP,adenosine diphosphate [ADP] and a phosphate group[symbolized as (P) are formed .

�some of the energy released is used to drive anabolic �some of the energy released is used to drive anabolic reactions such as the formation of glycogen from glucose.

Energy Transfer�Oxidation is the removal of electrons from a

substance.

�Reduction is the addition of electrons to substance.substance.

�Two coenzymes that carry hydrogen atoms during coupled oxidation-reductions are nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (NAD).

�ATP can generated via substrate-level phosphorylation, oxidative phosphorylation and photophosphorylation.

kreb’s cycle�The Krebs cycle named after the person who

discovered it in 1937, Hans Krebs is known by several other names including:

�The citric acid cycle�The citric acid cycle

�Tricarboxylaic acid cycle(TCA)

Contd. �The purpose of Krebs cycle is to link the aerobic and

anaerobic phases of metabolism in order to maximize ATP resynthesis.

�This is accomplished through the oxidation of high �This is accomplished through the oxidation of high energy organic compounds in the mitochondrial matrix.

�Since free electrons are unable to exist, the electrons released in an oxidation must be transferred to a carrier molecule.

Contd.�In order to apply these concepts to the Krebs cycle, one

must understand redox reactions and the process of ATP resynthesis.

Understanding of redox

reactions �Within a cell oxidation and reduction reactions are

always coupled.

�In other words, when one substance oxidized another is simultaneously reduced.is simultaneously reduced.

�Such coupled reactions are referred to as redox reactions.

The eight reactions of the Krebs

cycle�1)Entry of the acetyl group.the chemical bond that

attaches the acetyl group to coenzyme a(coA)breaks,and the two- carbon acetyl group attaches to a four –carbon molecule of oxaloacetic acid to form a six-carbonmolecule called citric acid.to form a six-carbonmolecule called citric acid.

�CoA is free to combine with another acetyl group from pyruvic acid and repeat the process.

�2)Isomerization.citric acid undergoes isomerization to isocitric acid, which has the same molecular formula as citrate.notice,however, that the hydroxel group (_oh)is attached to a different carbon.(_oh)is attached to a different carbon.

�3)Oxidative decarboxylation.isocitric acid is oxidized and loses a molecule of co2, forming alpha-ketoglutaric acid.the h- from the oxidation is passed on to nad+,which is reduced to Nadh+h+.on to nad+,which is reduced to Nadh+h+.

�4)Oxidative decarboxylation.alpha-ketoglutaric acid is oxidized ,loses a molecule of co2,and picks up coA to form succinyl coa.

�5)Substrate-level phosphorylation.coa is displaced by a phosphate group,which is then transferred to guanosine diphosphate (gdp) to form guanosine triphosphate (gtp).gtp can donate a phosphate group triphosphate (gtp).gtp can donate a phosphate group to adp to form ATP.

�6)Dehydrogenation.succinic acid is oxidized to fumaric acid as two of its hydrogen atoms are transferred to the coenzyme flavin adenine dinucleutide (fad),which is reduced to fadh2.dinucleutide (fad),which is reduced to fadh2.

�7)Hydration.fumaric acid is converted to malic acid by the addition of a molecule of water.

�8)Dehydrogenation.in the final step in the cycle,malic acid is oxidized to re-form oxaloacetic acid.two hydrogen atoms are removed are removed and one is transferred to nad+,which is reduced to nadh+h+.the transferred to nad+,which is reduced to nadh+h+.the regenerated oxaloacetic acid can combine with another molecule of acetyl coa,beginning a new cycle.

References � Tortora 2006.Principles of Anatomy and Physiology.

� Rose and Wilson,Anatimy and Physiology.