Upload
michelle-curva-9857
View
1.985
Download
1
Embed Size (px)
Citation preview
Derived Lipids
• STEROIDS– High molecular tetracyclic (4-ring) compounds– Sterols contain -OH groups but no C=O groups– Cholesterol (most common sterol)- found in animal fats
specifically in animal brain & nervous tissue, in the bloodstream
– Cholesterol aids in the absorption of fatty acids from the small intestine
– Some cholesterol of the body are derived or synthesized from other substances, e.g. CHO & proteins
– Cholesterol does not occur in plants
Derived Lipids
• Cholesterol – Also a plasma membrane component in all animal cells– Synthesized primarily in the liver– Aorta, skin, testes, adrenal cortex & intestines are also able
to synthesize it• Takes place in the microsomal & cytosomol fraction of the
cell– Hypolipidemic drugs may be used to lower serum
cholesterol• E.g. statin drugs which inhibit cholesterol synthesis
– Refer to case study 27-2 p 489
Derived Lipids
• Lipoproteins– Carriers of cholesterol– Contain a core of hydrophobic lipid molecules
surrounded by a shell of hydrophilic molecules such as proteins and phospholipids
– HDL (33% protein & 30% cholesterol) – LDL (25% protein & 50% cholesterol)– VLDL (carries TGL synthesized by the liver)– Chylomicrons (carry dietary lipids synthesized in the
intestines)
Derived Lipids
• Anabolic steroids - 18– Hormones that control the synthesis of larger
molecules from smaller ones– Athletes have used these substance to increase
muscle mass & body strength– E.g. testosterone
• Has many side effects, e.g., impotence, breast growth, increased masculinity, liver Ca
TRIGLYCERIDES
• triesters of glycerol and long-chain carboxylic acids• Also called triacylglycerols
FATS - 19• are esters formed by the combination of a fatty
acid with one particular alcohol, glycerol.• A mixture of TGL containing a high proportion of
long-chain, saturated fatty acids
OIL• A mixture of TGL containing a high proportion of
long-chain, unsaturated fatty acids or short-chain, saturated fatty acids
• Refer to Table 21.1 (average of fatty acids of some common fats and oils– Ex: beef tallow (animal fat)– Coconut oil (vegetable oil)
FATS & OILS
• Types of Fats/CholesterolSaturated fats-tend to raise blood cholesterol levels:
– fat in meat, skin of chicken and ducks,butter, lard, cream,milk and milk products, coconut and coconut products and palm kernel oil
Polyunsaturated fats- tend to lower total cholesterol level and LDL and raise HDL:– corn,soybean and safflower oils
Monounsaturated fats-tend to lower total chol. and LDL levels; HDL chol.levels remain unchanged:– canola oil and olive oil
FATS & OILS
How to Limit Intake of Saturated Fats• Minimize frying of foods• Avoid eating food drippings and gravy • Use vegetable oil in frying• Avoid the use of saturated fats and oils• Limit intake of spread and toppings-butter,margarine
and cream• Limit intake of bakery products, snack foods and other
processed foods• In general, AVOID oil or lard that is solid at room
temperature {tumitigas}
FATS & OILS
• Iodine Number– The # of grams of iodine that will react with double bonds
present in 100g of that fat or oil– The higher the iodine number, the greater the degree of
unsaturation of the fat or oil– Unsaturated fats & oils will readily combine with iodine– Saturated fats & oils will not– NOTE: The more unsaturated the fat or oil, the more
iodine it will react with– Generally, animal fats have a lower iodine # than do
vegetable oils, thus, vegetable oils are more unsaturated – The increasing unsaturation is associated with the change
of state of fats
FATS & OILS
• Iodine Number– Animal fats are solid, vegetable oils are liquid as degree of
unsaturation increases brought about by increased iodine number
• Use of fats in the body– Serve as a fuel – Produce more energy per gram than carbohydrate &
protein– Metabolism of fats produces 9kcal/g vs. CHO or protein
which produces 4kcal/g– Also serve as a reserve supply of food & energy for the
body
FATS & OILS
• Use of fats in the body– Stored in the adipose tissue & serves as a protector for the
vital organs• Surround & protect some vital organs & serve as shock absorber
– Also act as electrical insulators & allow rapid propagation of nerve impulses
– Constituents of lipoproteins & serve as a means of transporting lipids in the bloodstream
• Physical properties of fats & oils– Fats are white solids – Oils are yellow liquids– Both are odorless & tasteless
FATS & OILS
• Physical properties of fats & oils– Fats become rancid & develop an unpleasant odor & taste – Both are insoluble in water but soluble in organic liquids
• Benzene• Acetone• Ether
– Fats do not diffuse through a membrane; lighter than water & have a greasy feeling
– Fats and oils need first to be emulsified by bile in the body before they can be digested
FATS & OILS
• An oil is a substance that is in a viscous liquid state ("oily") at ambient temperatures or slightly warmer, and is both hydrophobic (immiscible with water) and lipophilic (miscible with other oils, literally).
• This general definition includes compound classes with otherwise unrelated chemical structures, properties, and uses, including vegetable oils, petrochemical oils, and volatile essential oils.
• Oil is a nonpolar substance.
FATS & OILS
• Chemical reactions that fat & oil undergo– HYDROLYSIS
• Form fatty acids & glycerol when treated with enzymes, acids, or bases
• When fats are hydrolyzed to fatty acids & glycerol, the glycerol separates from the fatty acids & can be drawn off & purified
• When purified, glycerol is used in medicine & industry– SAPONIFICATION
• Heating of a fat with a strong base, e.g., NaOH to produce glycerol & the salt of a fatty acid
• The Na+ or K+ salt of a fatty acid is called a SOAP
FATS & OILS
• Soaps & Detergents– Saponification of fats = soaps = 20– Soaps are salts of fatty acids; used as cleansing
agents– Detergents are sodium soalts of long-chain alcohol
sufates– Used for washing clothes & also as cleansing agents
FATS & OILS• Chemical reactions that fat & oil undergo
– HYDROGENATION• Changing of double bonds to single bond upon the
addition of hydrogen• Vegetable oils can be converted to fats by the addition of
hydrogen in the presence of a catalyst• Hydrogenation is used to produce vegetable shortenings
used in the home• Example: oleomargarine (made from hydrogenating
certain fats & oils, + some flavoring agents & coloring agents, + vitamins A & D
– ACROLEIN TEST• Test for the presence of glycerol• Used as test for fats & oils (all fats & oils contain glycerol)
FATS & OILS• Chemical reactions that fat & oil undergo
– ACROLEIN TEST• Glycerol is heated to a high temp w/ potassium bisulfate
(KHSO4)• Acrolein is produced which is recognizable by its strong,
pungent odor• Burned fats & oil has acrolein odor
– RANCIDITY - 19• Development of unpleasant odor when fats are allowed
to stand at room temp for a short period of time • They become rancid• Due to 2 types of reaction – HYDROLYSIS & OXIDATION• Can be inhibited by adding antioxidant to the product
FATS & OILS
• Chemical reactions that fat & oil undergo– RANCIDITY
• Antioxidants prevent oxidation, e.g. Vit C & E• Hydrolysis of butter can be prevented by keeping the
butter refrigerated & covered
FATS & OILS
• Waxes – Compound produced by the reaction of a fatty acid
with a high molecular mass monohydric alcohol– Primary esters of long-chain fatty acids with an even
number of carbon atoms– Widely used in cosmetics & ointments– Insoluble in water, non reactive, & flexible– Excellent protective coating, e.g. beeswax,
carnauba, lanolin, spermaceti
Role of Lipids in Cell Membranes
• Form the membranes around body cells and around small structures (organelles) inside the cells
• The cell membranes provide selective transport for nutrients & waste products into and out of cells
• Lipid bilayers– Hydrophobic– Hydrophilic
• Fluid mosaic model of membranes– Viscosity of substance for free movement
ABSORPTION OF CARBOHYDRATES• Monosaccharides are the products of digestion of CHO• Transported through the walls of the small intestine
directly into the bloodstream by– Passive transport/Diffusion– Active transport of galactose & glucose
• The blood carries the monosaccharides to the liver & then to the general circulation to all parts of the body
• The monosaccharides can be oxidized to furnish heat & energy
• Some are converted to glycogen (a polysaccharide)
ABSORPTION OF CARBOHYDRATES
• Glycogen are stored in the liver & muscles• The rest of the monosaccharides are converted to fat
& stored in the adipose tissue• Absorption therefore, can be illustrated as:
1. Monosaccharides → walls of small intestine Glucose → bloodstream
Fructose - active transportGalactose - passive transport
ABSORPTION OF CARBOHYDRATES
• Absorption therefore, can be illustrated as:
2. Blood → liver → general circulation (all parts of body)
-carries the mono-saccharides to
NOTE: REFER TO TABLE 25-1 p445 (Sackheim) SUMMARY OF DIGESTIONS
METABOLISM OF CARBOHYDRATES
OBJECTIVES• To recognize the significance of normal & abnormal
blood sugar levels• To describe the role of ATP in metabolism• To understand glycogenesis & glycogenolysis• To understand glycolysis & the HMP• To describe the role of oxidation in the citric acid cycle• To understand the electron transport system• To understand the role of gluconeogenesis
METABOLISM OF CARBOHYDRATES
OBJECTIVES• To discuss the overall scheme of carbohydrate
metabolism• To become familiar with the hormones involved in the
regulation of blood sugar levelRationale:The food we eat serves 2 main purpose• It fulfills our energy needs• It provides the raw materials to build the compounds our
bodies need
METABOLISM OF CARBOHYDRATES• Metabolism answers 2 major questions:
– How do cells obtain energy from the environment?– How do cells synthesize the building blocks of their
macromolecules?• Many reactions occur in metabolism but the number of kinds of
reactions is quite small --- these are the metabolic pathways• Stages of metabolism
– Biodegradation– Biosynthesis– Energy production thru Krebs cycle & oxidative phospho
METABOLISM OF CARBOHYDRATESBiodegradation • Breaking down of large molecules in food into small
units• Involves digestion & absorption
Biosynthesis • The smaller molecules are converted into a few very
simple units• These simple units play the central role in
metabolism
Role of Metabolism in Nutrition
Metabolism
• Metabolism – process by which living systems acquire and use free energy to carry out vital processes
• Catabolism (degradation)– Nutrients and cell constituents are broken down for
salvage and/or generation of energy– Exergonic oxidation
• Anabolism (biosynthesis)– Endergonic synthesis of biological molecules from
simpler precursors– Coupled to exergonic processes through “high-energy”
compounds
Role of Metabolism in Nutrition
Definition: the sum of all biochemical changes that takeplace in a living organism.
Group these reactions into two types:
anabolic catabolic
Reactions: require energy release energy
Produce: more complex more simple compoundscompounds
ModusOperandi: Occurs in small steps, each of which is controlled by specific enzymes.
Relationship Between Catabolic and Anabolic Pathways
• Catabolic pathways – Complex metabolites are transformed into simpler
products – Energy released is conserved by the synthesis of ATP
or NADPH
• Anabolic pathways – Complex metabolites are made from simple precursors – Energy-rich molecules are used to promote these
reactions
Examples of each type of metabolism:
Anabolic Pathways Catabolic Pathways
Protein Biosynthesis GlycolysisGlycogenesis TCA (Krebs cycle)Gluconeogenesis ß-oxidationFatty Acid Synthesis Respiratory Chain
Other useful generalizations:
Some of the steps in the anabolic path (going “uphill”) may not beidentical to the catabolic path--but some are shared.
ATPGeneratedProvidesEnergy
FOR
METABOLISM OF CARBOHYDRATESEnergy production • Krebs cycle• Oxidative phosphorylation
CONCENTRATION OF SUGAR IN THE BLOOD• Glucose, fructose & galactose (monosaccharides)
are end products of CHO digestion• Fructose & galactose are converted to glucose in
the liver so that the major monosaccharide remaining in the bloodstream is glucose
METABOLISM OF CARBOHYDRATES
• 70 – 100mg ( normal quantity of glucose present in 100ml of blood taken after a period of fasting) = NORMAL FASTING BLOOD SUGAR (FBS)
• Sugar level rises up to 120 – 130mg/100ml of blood or even higher soon after a meal, but drops soon as well after 1 ½ - 2hours and goes back to its normal level
• < 70 mg/ml blood sugar level (hypoglycemia)• > 100mg /ml blood sugar level (hyperglycemia)
METABOLISM OF CARBOHYDRATES
• Hypoglycemia symptoms include dizziness & loss of consciousness (because the brain metabolizes approximately 120 g of glucose daily, thus reducing the brain’s energy supply)
• HOW DOES THE BODY REGULATE THE AMOUNT OF GLUCOSE PRESENT IN THE BLOOD?
• WHAT HAPPENS WHEN THESE CONTROL MECHANISMS DO NOT FUNCTION PROPERLY?
METABOLISM OF CARBOHYDRATES
• When the glucose level in the blood rises, the liver removes the excess glucose & converts it to glycogen (a polysaccharide) = GLYCOGENESIS
• This glycogen is stored in the muscles & the liver• BUT only a certain amount of glycogen can be stored
in these organs• The rest is converted/changed to, and stored as, FAT
• Presence of glucose in urine is not normal (can be detected w/ the use of Benedict’s solution)
METABOLISM OF CARBOHYDRATES• Sugar becomes present in the urine when its blood
level rises above 170 – 180mg/100ml of blood (sugar spills over into the urine)
• In this event, excess glucose in the blood goes to the urine
• The point at which the sugar spills over into the urine is called renal threshold
• The presence of sugar in the urine is called glycosuria
• Spilling over of excess blood sugar to the urine is caused by several factors
METABOLISM OF CARBOHYDRATES
Factors:• Insulin secretion• Glycogenesis and storage as glycogen• Conversion to fat• Normal oxidation reactions in the body• Excretion through the kidneys when the renal
threshold is exceeded
METABOLISM OF CARBOHYDRATES
• 2-3 hours after eating, liver converts glycogen back to glucose (glycogenolysis)
• Stored liver glycogen is exhausted after 10 hours
• When this happens, the body makes the glucose now from amino acids – a non-carbohydrate source (gluconeogenesis)
41
Carbohydrate Storage & Synthesis
• Most of glucose consumed/day (80%) utilized by RBCs and brain.– 200g/day = total intake as a requirement.– Only 10g in plasma and 300g in liver.
• Blood glucose must be replenished constantly.– Consequences = hypoglycemia & coma
(<45mg/dL).– Glucose absorbed from intestine for 2-3 hr post
meals.
METABOLISM OF CARBOHYDRATESTHE METABOLISM OF CHO IN HUMANS IS CATEGORIZED
AS:• Glycogenesis (synthesis of glycogen from glucose)• Glycogenolysis (breakdown of glycogen to glucose)• Glycolysis (oxidation of glucose or glycogen to pyruvic or
lactic acid)• HMP (alternative oxidative path for glucose)• Krebs cycle (citric acid) & electron transport chain (final
oxidative path to CO2 & H2O)• Gluconeogenesis (formation of glucose from non-CHO)
43
Carbohydrate Storage & Synthesis
• Mechanism for maintenance of blood glucose between meals.
– Glycogenesis - liver conversion of glucose to glycogen for storage.
– Glycogenolysis - liver degradation of glycogen stores to glucose.• Hepatic glycogen not sufficient during 12 hr fast.
44
Carbohydrate Storage & Synthesis
• Mechanism for maintenance of blood glucose between meals.– Glyconeogenesis - during sleep shift from
glycogenolysis to de novo synthesis of glucose in liver; essential during fasting or starvation.
• Amino acids form muscle proteins.• Lactate from glycolysis.• Glycerol from fat metabolism.
– Lipids from adipose tissue.
45
Carbohydrate Storage & Synthesis
• Mechanism for maintenance of blood glucose between meals.– Muscle glycogen.
• Not available for blood glucose.• Muscle energy metabolism.
– Primarily from fats.– Glucose for bursts of physical activity.– On a tissue mass basis majority of glycogen is
stored in muscle.
METABOLISM OF CARBOHYDRATES
GLYCOGENESIS• The formation of glycogen from glucose• Occurs primarily in the liver & the muscles• Liver contain up to 5% glycogen after a high CHO
meal• May contain almost zero glycogen after 12 hours
of fasting
C6H12O6 (C6H10O5)n + H2O
glycogenesis
glycogenolysisglycose glycogen
METABOLISM OF CARBOHYDRATES
Steps in glycogenesis:1. Conversion of glucose to glucose-6-phosphate
(glucose 6-P) (a phosphate ester of glucose)– ATP from the liver cells serves as a source of the
phosphate group– After the loss of the phosphate group, ADP is left– Glucokinase is the enzyme necessary to catalyze
this reaction– While insulin is involved in the phosphorylation of
glucose by glucokinase
METABOLISM OF CARBOHYDRATES
Steps in glycogenesis: Conversion of glucose to glucose-6-phosphate (glucose 6-P) (a
phosphate ester of glucose)
Glucose + ATP glucose 6-P + ADP2. rearrangement/repositioning of glucose 6-P to produce glucose
1-phosphate
glucose 6-P glucose 1-P
glucokinase
insulin
phosphoglucomutase
METABOLISM OF CARBOHYDRATES
Steps in glycogenesis:3. Reaction of glucose 1-P w/ uridine triphosphate (UTP) to form uridine diPO4
glucose (UDPG)
glucose 1-P + UTP UDPG + pyrophosphate
4. Glucose molecules in UDPG (activated glucose molecules) are joined together to form glycogen
• Enzymes necessary are glycogen synthetase & a branching enzyme
UDPG pyrophosphorylase
METABOLISM OF CARBOHYDRATES
Steps in glycogenesis:4. Glucose molecules in UDPG (activated glucose molecules) are joined
together to form glycogen• Glycogen synthetase enzyme is regulated by insulin & cyclic adenosine
monophosphate (cAMP)• cAMP aids in the formation of glycosidic linkages
UDPG glycogen + UDP
glycogen synthetase
branching enzyme(transglycosylase)
METABOLISM OF CARBOHYDRATES
Steps in glycogenesis:5. UDP formed from step 4 reacts w/ ATP to regenerate UTP.
UDP + ATP UTP + ADP
NOTE:REFER TO Fig 26-4 p 458 OVER ALL REACTION OF GLYCOGENESIS
52
METABOLISM OF CARBOHYDRATES
GLYCOGENOLYSISSteps:1. Conversion of glycogen to glucose 1-phosphate by the enzyme
phosphorylase A 2. Glucose 1-P to glucose 6-phosphate by the enzyme
phosphogucomutase3. Glucose 6-P is coverted to glucose by the enzyme G-6 phophatase
(found in the liver but not in the muscle, thus muscle glycogen cannot serve as a source of blood glucose)
METABOLISM OF CARBOHYDRATES
• cAMP (cyclic adenosine monopgosphate) – Involved in the conversion of glucose into G 6-P in both the liver & the
muscles– The body produces hormone when it is under stress– The hormone produced are carried by the blood stream to the liver cells– In the liver cells, these hormones activate the enzyme adenyl cyclase– This adenyl cyclase causes the production of cAMP from ATP– cAMP activates a protein kinase
METABOLISM OF CARBOHYDRATES
• cAMP (cyclic adenosine monopHosphate) – This protein kinase activates a phosphorylase b kinase– This phosphorylase b kinase activates phosphorylase a– This phosphorylase a triggers the conversion of glycogen into glucose
• This is how cAMP is involved in glycogenolysis• Glycogen is normally stored in the liver & the muscles• When glycogen is not reconverted to glucose, it begins to accumulate (a
genetic disease)• This genetic disease is called VON GIERKE’S DISEASE
METABOLISM OF CARBOHYDRATES
• In this disease, the liver lacks the enzyme glucose 6-phosphatase
• For this reason glycogen accumulates in the liver• Conditions brought by lack of the enzyme in the liver
– Hypoglycemia– Ketosis– Hyperlipidemia – Enlargement of the liver because of the increased amount of
glycogen stored
METABOLISM OF CARBOHYDRATES• A lack of lysosomal enzyme that acts in breaking down of
glycogen causes accumulation of glycogen in this organ • This disease is POMPE’S DISEASE• Absence of a debranching enzyme in the liver also causes
accumulation of glycogen that brings about the FORBE’S DISEASE or CORI’S LIMIT DEXTRINOSIS
• Other glycogen storage diseases– Andersen’s disease– McArdle’s syndrome– Tarui’s disease
METABOLISM OF CARBOHYDRATES
• Andersen’s disease– Death occurs in the 1st year of life because of liver & cardiac
failure)• Mcardle’s syndrome
– Individuals have great reduction in tolerance to exercise because of lack of a muscle enzyme involved in glycogenolysis
• Tarui’s disease– Caused by phosphorylase deficiency in the liver
METABOLISM OF CARBOHYDRATES
KEY MESSAGES:• Liver (hepatic) cells can consume the glucose-6-
phosphate in glycolysis, or remove the phosphate group using the enzyme glucose-6-phosphatase and release the free glucose into the bloodstream for uptake by other cells.
• Muscle cells in humans do not possess glucose-6-phosphatase and hence will not release glucose, but instead use the glucose-6-phosphate in glycolysis.
METABOLISM OF CARBOHYDRATES
• The most common type of glycolysis is the Embden-Meyerhof pathway– first discovered by Gustav Embden and Otto Meyerhof
• Glycolysis also refers to other pathways, such as the Entner-Doudoroff Pathway
• EMBDEN-MEYERHOF PATHWAY is the breakdown of glycogen to pyruvate (pyruvic acid) & lactate (lactic acid)– 1st phase of muscle contraction– An anaerobic process (can take place even w/o oxygen)
METABOLISM OF CARBOHYDRATES
• EMBDEN-MEYERHOF PATHWAY is the breakdown of glycogen to pyruvate (pyruvic acid) & lactate (lactic acid)– Glycolysis supplies the ATP needed for muscle contraction– More than 90% of the energy in the RBCs is produced by
glycolysis– Overall reaction:
G6P + 2ADP → 2 pyruvic acid (or pyruvate) + 2ATP(from glycogen or glucose)
METABOLISM OF CARBOHYDRATES
Steps in glycolysis:1. G6P is converted to fructose 6-phosphate
G6P → F6P phosphoglucose isomerase
2. F6P is converted to fructose 1, 6-diPO4 ****
F6P → F1, 6-diPO4phosphofructokinase
**** ATP is converted to ADP
METABOLISM OF CARBOHYDRATES
Steps in glycolysis:3. F1, 6-diPO4 is converted to glyceraldehyde 3-PO4 &
dihydroxyacetone PO4
F1, 6-diPO4 → glyceraldehyde 3PO4 + dihydroxyacetone PO4 aldolase
4. glyceraldehyde 3-PO4 is converted to 1,3-diphosphoglycerate ****NAD is reduced to NADH + H
glyceraldehyde 3PO4 → 1,3-diphosphoglycerateglyceraldehyde 3-PO4 dehydrogenase
METABOLISM OF CARBOHYDRATESSteps in glycolysis:5. 1,3-diphosphoglycerate → 3-phosphoglycerate****
phosphoglycerokinase **** 2ADP’s are changed to 2ATPs6. 3-phosphoglycerate → 2-phosphoglycerate
phosphyglyceromutase7. 2-phosphoglycerate → phosphoenolpyruvate
enolase8. Phosphoenolpyruvate → pyruvate****
pyruvic kinase
METABOLISM OF CARBOHYDRATESSteps in glycolysis:
**** 2 ADPs are changed to 2 ATPs9. Pyruvate → lactate****
lactic dehydrogenase
**** NADH & H+ are changed to NAD+**** lactic acid is a metabolic dead end
• LACTACIDOSIS is the condition caused by accumulation of lactic acid due to lack of lactic dehydrogenase– Fatal condition if untreated
METABOLISM OF CARBOHYDRATES• Phosphofructokinase
– Allosteric enzyme controlling the rate of glycolysis– Inhibited by high levels of ATP– Stimulated by low levels of ATP– Provides compounds for biosynthesis
HEXOSE MONOPHOSPHATE SHUNT (HMP)– An important series of reaction because it provides
the 5C- sugars (pentose) – This pentose is needed for the synthesis of nucleic
acids & nucleotides
METABOLISM OF CARBOHYDRATESHEXOSE MONOPHOSPHATE SHUNT (HMP)
– The pentose makes the availability of NADPH– The NADPH is the reduced form of NADP+– The NADP+ is a co-enzyme necessary for the
synthesis of fatty acids and steroids– HMP pathway is more active in adipose tissue than in
muscle– ATP is not generated in this sequence
• Hemolytic anemia– Disease caused by a genetic deficiency of enzyme
G6P dehydrogenase
METABOLISM OF CARBOHYDRATES
• Lack of G6P dehydrogenase also provides resistance to MALARIA
• But lack of this enzyme also reduces the level of NADPH in RBCs
• This NADPH in the RBCs is necessary for the maintenance of proper levels of the antioxidase glutathione
• Inadequate glutathione makes the easy oxidation of RBCs by variety of drugs
METABOLISM OF CARBOHYDRATESKey Messages:• The pentose phosphate pathway (also called
phosphogluconate pathway, or hexose monophosphate shunt [HMP shunt]) is a process that serves to generate NADPH and the synthesis of pentose (5-carbon) sugars.
• There are two distinct phases in the pathway. – The first is the oxidative phase, in which NADPH is
generated, and – the second is the non-oxidative synthesis of 5-carbon
sugars.
METABOLISM OF CARBOHYDRATES
Key Messages:• This pathway is an alternative to glycolysis. • While it does involve oxidation of glucose, its
primary role is anabolic rather than catabolic.
THE CITRIC ACID CYCLE• also known as the tricarboxylic acid cycle (TCA
cycle), the Krebs cycle, or more rarely, the Szent-Györgyi-Krebs cycle
METABOLISM OF CARBOHYDRATES
THE CITRIC ACID CYCLE• a series of enzyme-catalyzed chemical reactions of
central importance in all living cells that use oxygen as part of cellular respiration
• In eukaryotes, the citric acid cycle occurs in the matrix of the mitochondrion
• In aerobic organisms, the citric acid cycle is part of a metabolic pathway involved in the chemical conversion of carbohydrates, fats and proteins into carbon dioxide and water to generate a form of usable energy
METABOLISM OF CARBOHYDRATES
STEPS OF CITRIC ACID CYCLE1. Formation of active acetate from pyruvic acid
– This active acetate is acetyl CoA which is the converting substance in carbohydrates, fats, & proteins metabolism
– Acetyl CoA becomes the fuel for the Krebs cycle
2. Reaction of acetyl CoA with oxaloacetic acid and goes through the cycle
3. Oxaloacetic acid is regenerated & picks up another molecule of acetyl CoA to carry it to the sequence
METABOLISM OF CARBOHYDRATES
STEPS OF CITRIC ACID CYCLE4. Oxidation of acetyl CoA to CO2
– In this reaction, NADH & FADH2 are produced
5. NADH & FADH2 enter into the electron transport chain that functions on the inner membranes of the mitochondria
Note: detailed steps on a separate sheet
METABOLISM OF CARBOHYDRATES
Summary of the TCA cycle:
Acetyl CoA + 3NAD+ + FAD + GDP + P + 2 H2O
↓
2 CO2 + CoA + 3 NADH + 2 H+ + FADH2 + GTP
METABOLISM OF CARBOHYDRATES
Role of B Vitamins in the TCA Cycle• B2 (Riboflavin) in the form of flavin adenine
dinucleotide – Cofactor in the alpha-ketoglutarate dehydrogenase
complex & in succinate dehydrogenase
• B1 (thiamine) – Coenzyme for the decarboxylation in the alpha-
ketoglutarate dehydrogenase reaction
• Niacin in the form of NAD+– Coenzyme for the dehydrogenases in the cycle
METABOLISM OF CARBOHYDRATESRole of B Vitamins in the TCA Cycle• Pantothenic acid
– A part of coenzyme A
ELECTRON TRANSPORT SYSTEM• couples a chemical reaction between an electron
donor (such as NADH) and an electron acceptor (such as O2) to the transfer of H+ ions across a membrane, through a set of mediating biochemical reactions
METABOLISM OF CARBOHYDRATES
ELECTRON TRANSPORT SYSTEM• These H+ ions are used to produce adenosine
triphosphate (ATP), the main energy intermediate in living organisms, as they move back across the membrane
• Electron transport chains are used for extracting energy from sunlight (photosynthesis) and from redox reactions such as the oxidation of sugars (respiration).
• The overal reaction is also called OXIDATIVE PHOSPHORYLATION
METABOLISM OF CARBOHYDRATES
GLUCONEOGENESIS• Formation of glucose from non CHO substances,
e.g. amino acids, glycerol• Takes place primarily in the liver• Also occurs in the kidneys to some extent• It meets the body’s needs for glucose when
sufficent CHO is unavailable• Increased by high protein diets; decreased by
high CHO diets
METABOLISM OF CARBOHYDRATES
GLUCONEOGENESIS• a metabolic pathway that results in the generation
of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids.
• An ubiquitous process, present in plants, animals, fungi, and other microorganisms
• In animals, gluconeogenesis takes place mainly in the liver and, to a smaller extent, in the cortex of kidneys
METABOLISM OF CARBOHYDRATESGLUCONEOGENESIS• This process occurs during periods of fasting,
starvation, or intense exercise and is highly endergonic
• often associated with ketosis
• also a target of therapy for type II diabetes, such as metformin, which inhibit glucose formation and stimulate glucose uptake by cells
METABOLISM OF CARBOHYDRATESInterconversion of hexoses• Meals contaning starch, sucrose & lactose loads
the liver with galactose & fructose, which must be converted into glucose
• GALACTOSEMIA is the disease associated with the inability to convert galactose into glucose
• High levels of galactose produce mental retardation & cataracts
• The condition is reversed once all galactose-containing foods are removed, except for mental retardation
METABOLISM OF CARBOHYDRATESHormones involved in regulating blood sugar ----• The liver plays a vital function in controlling the
normal blood sugar level by removing sugar from & adding sugar to the blood
• This function is controlled by some hormones– Insulin– Epinephrine– Glucagon– Hormones of the anterior pituitary, adrenal cortex,
and the thyroid
METABOLISM OF CARBOHYDRATES
INSULIN• Produced by beta cells of the islets of Langerhans
in the pancreas• Principal function
– Removal of glucose from the bloodstream and a consequent lowering of blood sugar level
• Diabetes mellitus– Decreased secretion of insulin because of decreased
activity of alpha islets of langerhans will cause rising of blood sugar
METABOLISM OF CARBOHYDRATESINSULIN• Diabetes mellitus
– Increased blood sugar level(hyperglycemia) leads to glycosuria (glucose in the urine) because the renal threshold is exceeded
EPINEPHRINE• Secreted by the medulla of the adrenal glands• Stimulates formation of glucose from glycogen in
the liver
METABOLISM OF CARBOHYDRATES
GLUCAGON• Produced by alpha cells of the pancreas• Raises blood sugar levels by stimulating the
activity of the enzyme phosphorylase in the liver, which changes liver glycogen to glucose
• Also increases gluconeogenesis from amino acids & from lactic acid
METABOLISM OF FATS
• DIGESTION OF FATS & PHOSPHOLIPIDS– Fats & phospholipids are emulsified then hydrolyzed
into fatty acids & glycerol
Fats & phospholipids fatty acid & glycerol emulsification
Fatty acid & glycerol triglycerides (resynthesized fats)
synthesis (in the intestinal mucosa)
thoracic duct
bloodstream
METABOLISM OF FATS
• DIGESTION OF FATS & PHOSPHOLIPIDS– Because fats & phospholipids are insoluble in the
blood (& water), they form complex with plasma protein (water soluble)
– The complexes formed are called LIPOPROTEINS– Then they will be transported by the blood
• Absorption of fat– Takes place primarily in the small intestine– Occurs by hydrolysis yielding fatty acids & glycerol– Before digestion happens, fat emulsification by the
bile salts should take place
METABOLISM OF FATS
(Small intestine) (lacteals of the villi to the lymphatics)hydrolysis→ fatty acid & glycerol→ resynthesized fats ↓
thoracic duct ↓bloodstream ↓
cells ← phospholipids ← liver(fats are oxidized (sphingomyelin & lecithin)
to furnish heat & energy) -necessary for formation of ↓ nerve & brain tissue
excess fats are stored as adipose - cephalin (for blood clotting) tissue
89
Digestion of Dietary Triacylglycerols
• Occurs in duodenum• Facilitated by
• Bile salts (emulsification)• Alkaline medium (pancreatic juice)
Pancreaticlipases
OH
OH
TAG MAG
Intestinallipases Glycerol
+Fatty Acids
Blocked by Orlistat (“Fat Blocker”) - Xenical/Alli