fats and fatty acids Flashcards
LIPIDS: CLASSIFICATION
what are htey made of
composed of C, H and O • ratio of O to C's and H's lower than with CHO • relatively insoluble in H2O • soluble in nonpolar solvents – e.g., ether, chloroform, benzene • energy releasing nutrient
A. Simple Lipids
- Fatty acids (FAs)
- Neutral fats - monoglycerides (MG)
- diglycerides (DG)
- triglycerides (TG)
[triacylglycerols] - Waxes - esters of FAs with ↑ alcohols
a. Sterol esters: e.g,, cholesterol esters
b. Non-sterol esters: e.g., Vit A esters, etc
B. Compound Lipids
- Phospholipids
a. Phosphatidic acids
e. g., lecithin, cephalins
b. Plasmalogens
c. Sphingomyelins - Glycolipids - carbohydrate containing
- Lipoproteins - lipids associated with ptn
C. Derived Lipids
derivatives formed from A and B • possess general properties of lipids • soluble in organic solvents – e.g., ether, chloroform, acetone • fat-soluble vitamins • corticosteroid hormones • coenzyme Q (electron transport)
STRUCTURE AND FUNCTION
FATTY ACIDS (FAs)
Basic unit of lipids is FA
- building block of other lipids
defined by # of Cs and presence of double bonds
H3C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C=O
|
OH
nonpolar(omega end), hydrophobic polar, hydrophillic
(lengthening end)
No double bonds (DB): Saturated
With double bonds (DB): Unsaturated - 1, 2, 3 or 4 DBs
- cis or trans (cis common)
even # Cs in FA: naturally occurring (plants/animals)
odd # Cs in FA: occur is small amts in food
Physical Properties:
Melting point of a FA (and TG containing it) will ↓ with:
1. the shorter the chain
2. the higher the degree of unsaturation i.e., # of DBs
Hydrogenation:
- UFA → SFA ( liquid → solid )
- adding H+ to DBs (less rancid, ↓ [O])
- cis UFA → SFA → cis UFA or trans UFA
- used for “margarine” production
- trans FAs are UFAs but act like SFA
i.e., solid, no EFA properties, ↑ blood cholesterol
- consumer beware (food labels)
Fatty Acids: Names & Sources
If chain is short: Short Chain (Volatile) FA
2:0 = acetic (GI fermentation)
3:0 = propionic (GI fermentation)
4:0 = butyric (butter, GI)
If chain is medium length (6-14C): Medium Chain FA
12:0 = lauric
14:0 = myristic
Fatty Acids: Names & Sources
If chain is long (16-20C): Long Chain FA 16:0 = palmitic (common) 18:0 = stearic (common) 20:0 = arachidic There are fatty acids with C>20 Very Long Chain FAs
One double bond = monounsaturated (MUFA)
H3C-C-C-C-C-C-C-C-C=C-C-C-C-C-C-C-C-C=O | OH 16:1 = palmitoleic 18:1 = oleic (olive) [common]
2 or more double bonds = polyunsaturated (PUFA)
H3C-C-C-C-C-C=C-C-C=C-C-C-C-C-C-C-C-C=O | OH "ω" or "n" delta (Δ) 18:2(9,12) 18:2Δ9,12 18:2ω6 18:2n6 = linoleic 18:3(9,12,15) 18:3Δ9,12,15 18:3ω3 18:3n3 = α-linolenic 20:4n6 = arachidonic 20:5n3 = eicosapentaenoic
3 families of unsaturated FAs:
- n-3 = ω3 = delta 9,12,15
18: 3n3 → 20:5n3 (eicosapentaenoic [EPA] fish)
- classified as “essential” (α-linolenic)
- 20:5n3 precursor to “eicosanoids” (PG3)
- hypolipidemic, antithrombotic effects
- 22:6n3 (docosahexenoic acid - fish)
- membrane phospholipid, cerebrum
3 families of unsaturated FAs:
- n-6 = T6 = delta 9,12
18:2n6 → γ-linolenic (18:3n6)→ 20:3n6 → 20:4n6
seeds (18:2n6 linoleic ) → 20:3n6 → 20:4n6 → PG2
└→ PG1
animals (20:4n6 arach) → PG2
- classified as “essential” (linoleic)
3 families of unsaturated FAs:
- n-9 = delta 9
16:0 → 18:0 → 18:1 (oleic) → ≠ 18:2n6
→ ≠ 18:3n3
- animals can convert (18:0 → 18:1→ 20:3)
- no known function of 20:3
Eicosanoids:
arachidonic acid (20:4n6)* eicosatrienoic acid (20:3n6) eicosapentaenoic acid (20:5n3)* ↓ [Ox] prostaglandins (P) thromboxanes (T) leukotrienes (L) * more common in food
Prostaglandins
18:2n6 → PG1 & PG2 20:4n6 → PG2 18:3n3 → PG3
- 20 Cs, 5 C ring, # DBs, small structural difference
e.g., PGD, PGE, PGF, PGI, PGG, PGH
Eicosanoid Function:
- immune fn effects
- gastric secretions
- vasodilators (↓ BP) or vasoconstrictors,
- ↑ smooth muscle contraction
- ↓ or ↑ platelet aggregation
NEUTRAL FATS
Triglycerides (TG) = Triacylglycerols
TG = glycerol + 3 FAs (ester bonds)
- simple TG = same FAs / mixed TG = different FAs
- “high energy” storage form of body fat
- adipose TG → free FA → body tissue → OX
- 95% of dietary fat as TGs
- TG exist as fats (solids) or oils at room temp
- depends on FA composition (oil = SCFAs and ↑ DBs)
Diglycerides (DG) = glycerol + 2 FAs
Monoglycerides (MG) = glycerol + 1 FA
- negligible in tissues
- intermediate in some metabolic reactions
e.g., lipases - digestion, hydrolyse TG
- component of other lipids
- in food, emulsifying agents
STEROLS AND STEROIDS
steroid = 4-ring hydrocarbon structure sterol = monohydroxy alcohol of steroid e.g., - cholesterol synthesized in animals - other sterols found in plants e.g., ergosterol) Cholesterol - NB component of cell membrane - precursor for other steroids cholesterol + FA = cholesterol ester
PHOSPHOLIPIDS
5% of fat intake
– food emulsifiers, plants & animals
1. glycerol + 2 FAs [1,2 Cs] + (Pi + base [3 C])
base = choline (lecithin), inositol etc
2. sphingomyelins (FA + Pi + sphingosine)
- myelin sheath of nerve tissue
- polar structures (hydrophillic properties)
- chylomicrons
- cell and organelle membranes (regulator of passage)
GLYCOLIPIDS (GL)
backbone of GL (Ceramide = FA + sphingosine)
- GL contains no Pi
Cerebrosides - ceramide + monosaccharide (MS)
(GLU,GAL)
Gangliosides - ceramide + oligosaccharide
(MS derivative)
- structure of cell membranes
- “recognition markers” on exterior of membrane
- cell identity (NB for immune system)
LIPOPROTEINS (LP)
transport form of lipids in blood - 5 main classes: chylomicrons very low density lipoptn (VLDL) intermediate density lipoptn (IDL) low density lipoptn (LDL) high density lipoptn (HDL) Plus: FFA bound to albumin
omega-3 vs omega 6
3 makes the 3
6 makes the 1 and 2
giglycerides
glycerol + 2 FAs
Monoglycerides (MG)
glycerol + 1 FA
NEUTRAL FATS
Diglycerides (DG) = glycerol + 2 FAs Monoglycerides (MG) = glycerol + 1 FA - negligible in tissues - intermediate in some metabolic reactions e.g., lipases - digestion, hydrolyse TG - component of other lipids - in food, emulsifying agents-
STEROLS AND STEROIDS
steroid = 4-ring hydrocarbon structure sterol = monohydroxy alcohol of steroid e.g., - cholesterol synthesized in animals - other sterols found in plants e.g., ergosterol) Cholesterol - NB component of cell membrane - precursor for other steroids cholesterol + FA = cholesterol ester
steroid
steroid = 4-ring hydrocarbon structure
sterol =
monohydroxy alcohol of steroid (added OH on the molecules)
e. g., - cholesterol synthesized in animals
- other sterols found in plants
e. g., ergosterol)
cholesterol ester
cholesterol + FA
PHOSPHOLIPIDS
(95% as triglycerides) 5% of fat intake (from cell membranes)
– food emulsifiers, plants & animals
1. glycerol + 2 FAs [1,2 Cs] + (Pi + base [3 C])
base = choline (lecithin(eggs)), inositol etc
2. sphingomyelins (FA + Pi + sphingosine)
- myelin sheath of nerve tissue
- polar structures (hydrophillic properties)
- chylomicrons
- cell and organelle membranes (regulator of passage)
the phosphate group is the hydrophylic part, (2 fa and a phosphate group and a pase
sphingomyelin
ceramide with a choline(base) with a phosphate group
GLYCOLIPIDS (GL)
- backbone of GL (Ceramide = FA + sphingosine)
- GL contains no Pi
Cerebrosides - ceramide + monosaccharide (MS)
(GLU,GAL)
Gangliosides - ceramide + oligosaccharide
(MS derivative) - structure of cell membranes
- “recognition markers” on exterior of membrane
- cell identity (important for immune system)
ceramide
sphingogosine with faty acid
Cerebrosides
- ceramide + monosaccharide (MS)
GLU,GAL
Gangliosides
- ceramide + oligosaccharide
MS derivative
LIPOPROTEINS (LP)
5 main kinds
wont ever ask us to draw but know what theyre made up of,
- transport form of lipids in blood
- 5 main classes: chylomicrons (82% triglyceride, 7% phospholipids, 2% cholesterol9% protein)
very low density lipoptn (VLDL) (54% tryglyceride, 18%phospholipds, 22% cholesterol, 7% protein- made in the liver to transport extra fats from liver from diet to tissue, high in phospholipids because made in liver tot ransport to other tissues to rejevenate cell membranes, high in cholesterol from liver (made there)liver making fats to destribute to rest of body)
intermediate density lipoptn (IDL)( 31% triacylglyceride, 22%…)
low density lipoptn (LDL) (9% triacylglecerides, 23% phospholipid, 47% cholesterol, droped off tri to the adipose tissue - the “bad” cholesterol, 21% protein )
high density lipoptn (HDL)( 3% tri, 28% phospholipids, 19% cholesterol, 50% protein - rejevinate cell membrane and pick up LDL cholesterol
Plus: FFA bound to albumin (very dense lipoprotein, no apoprotein coding)
outer layer of protein,
improve HDL by physical activity, MUFAS,
chylomicron half life is really short just from intestine to the liver- about 1 hour, LDL stick around
MAJOR FUNCTIONS OF LIPIDS
IN THE BODY:
- As a compact storage of NRG (TG)
- As thermal insulator (TG in adipose tissue)
- As a “cushion” to support internal organs
• e.g., kidneys (TG in adipose) - As a constituent of membranes of all cells and cell organelles
• PL, GL, sterols - As a constituent of myelin sheath
• complex/derived fats, e.g., cerebrosides - Precursors to essential compounds (FAs)
e.g., eicosanoids: PG, thromboxane, leucotriene
18:2n6→→→18:3n6 → 20:3n6 (→PG1) → 20:4n6 → PG2
18:3n3 → 20:4n3 → 20:5n3 →PG3
MAJOR FUNCTIONS OF LIPIDS
B. AS A FOOD COMPONENT:
- High energy value (9 kcal or 38 kJ per gram)
- As a source of essential fatty acids (EFAs)
- As a medium for fat-soluble vitamins and a
requisite for their digestion and transport in the
blood from absorption - Provide flavour and aroma to food
- High satiety value (delay gastric emptying)
Dietary Sources & Health Implications
• Foods containing MCFAs (10-14 Cs):
coconut, palm kernel (“tropical oils”), MCT oil
- liquid at room temperature
- SFA but not long chain
- ↓ intake since these ↑ serum cholesterol,
especially LDL
NOT PART OF MICELLE- WHICH GOES TO CHYLOMICRON TO THE LYMPHATIC SYSTEM- PPL WITH BAD LYMPH SYSTEM TAKE THESE FATS FOR ENERGY
Dietary Sources & Health Implications
• Foods containing long chain (LC) SFA:
dairy, lard, tallow (“animal”), cocoa
SFA: suggest ↓ to <10% energy
- solid at room temp
Dietary Sources & Health Implications
• Foods containing MUFA:
olive, canola, peanut
MUFA do not raise serum cholesterol
- use to replace SFA
- extra fat as MUFAs (Mediterranean Diet)
good SUBSTITUTE FOR SATURATES
Dietary Sources & Health Implications
• Foods containing PUFA as n-6:
seed oils: corn, soy, safflower (linoleic 18:2n6,9)
18:2n6,9 → (desaturation) → 18:3n6,9,12 (GLA)
- primrose, borage (supplement)
• Foods containing PUFA as n-3:
18:3n3,6,9 = α-linolenic
canola 10%, linseed, soy 7% (vegetables n-3)
20:5n3 = eicosapentaenoic (EPA)
fish: fatty fish or fish liver oils
PUFAs and MUFAs
Want M&P/S ratio > 1 - so can ↓ S and ↑ M&P without ↑ total fat - too much P not good → eicosanoids problems
more monos and pufas than saturated
prostaglandins- heart health, can be vasoconstrictor if too much because participate in platelets- dont go crazy on the 6s
DIGESTION AND ABSORPTION
pancreatic lipase breaks them down
4 interacting factors are essential for normal fn of the
intestines in fat absorption:
1. secretion of hydrolytic enzymes from pancreas to break
ester linkages of TG
2. release of detergents (bile salts) in the bile to emulsify
fats and breakdown products
3. uptake of digestion products into mucosal cells (villi) of SI
4. conversion of digestion products into particles for
transport from MCs to lymph system & blood
DIGESTION AND ABSORPTION
Failure:
fat in the faeces (i.e., steatorrhoea)
- diarrhoea
- H2O & electrolyte loss
- ↓ absorption of nutrients
- fat soluble vitamins
- starvation
DIGESTION
LIPOLYSIS:
hydrolysis by pancreatic enzymes called lipases
- in duodenum, - lipids mix with secretions
- emulsions form
- lipases act
TG → 2-MG + 2FAs → Na salts (TG/DG ≠ absorbed)
DIGESTION
BILE SALTS AND MICELLES:
bile salts: - detergents (hydrophilic & hydrophobic) - formed by [O] of cholesterol in liver - "mixes" with lipids (↑ surface area) - form emulsions → lipase attack - part of micelles → absorption (enterohepatic circulation)
micelles: - bulky hydrophilic ends outside (aqueous)
- narrow hydrophobic ends inside
- smaller than emulsions
- absorbed by mucosal cell of SI
ABSORPTION
of bile salts
- Micelles (MG and FFAs) absorbed into MC
- glycerol, SCFAs, MCFAs absorbed directly
- do not require to be part of micelle
- absorbed into MC → blood - MG and FFAs reesterified → TG
- requires nrg (FA activated to acyl-CoA deriv) - TG, cholesterol, chol esters, PLs, fat sol Vits
→ stabilized by surface layer of ptn and PLs
- lipid droplet discharged from MC
- chylomicron (CM) - CM enter lymphatics → blood (thoracic duct)
- Circulating CM → lipoptn lipase → FAs
+ glycerol
- after meal, ↑ FA → adipose (↑ insulin)
- also FAs → ↑ other body tissues
- glycerol / CM remnants taken up by liver
- “clearance” of CM = ½ time < 1 h in humans
chylomicron is composed of
phospholipids, cholesterol, protein, triacylglyceride (made from fatty acids, monoacylglycerol)
albumin
direct absorption of short chian free fatty acids
METABOLISM
IN LIVER
IN LIVER
1. SCFAs → portal circulation (via plasma albumin) → liver → FA [O]
2. bile salt (BS)
portal circulatn → liver → BS pool → bile duct → SI →
recycling: enterohepatic circulation
3. other lipids enter liver via the hepatic artery
1. CMR (eg, sterols) → blood → membrane receptors
2. Adipose → FFAs → blood (via albumin) → FA [O]
where do bile salts go
not part of chylomicron- goes to lipid from portal vein
LIPID METABOLISM: LIVER
- hepatic cells play central role in lipid metabolism:
1. FA [O] (exogenous lipids)
2. FA synthesis (endogenous lipids from glu)
3. biosynthesis of cholesterol (and bile salts)
4. formation of phospholipids (of blood plasma)
5. formation of lipoproteins
6. regulatory role in storage of fats in tissues
(fat storage in liver is small < 1% of mass) - regulatory role of liver fails: fatty liver
e.g., toxicity (ie, EOH)
7. production of ketone bodies (alternative nrg)
2 types of fatty liver disease
non-alcoholic liver disease,
cirhosis
- FATTY ACID OXIDATION
• in “fasted state”, FAs important nrg source
– liver priority: glycogen → glu → oblig glu users
• compact fuel (> nrg produced)
• lipids consist mainly of C & H:
– [O] involves consumption of»_space; O2
– Thus, > ATP production
[O] PATHWAY
- mitochondria (linked to TCA cycle and e- TC)
1. activation of FAs to acyl-CoA thio esters
• requires nrg [also step in making fats / PLs]
2. mitochondria entry of FA-CoA requires carnitine
(carrier molecule)
3. β oxidation
• cyclic series of rxns where Hs removed and 2C units split off as
acetyl-CoA (come off in twos- 18c= 8 cycles, 16c=7cycles)
4. TCA [O] of acetyl CoA to yield H and CO2
• nrg yield from complete [O] is great:
• β oxidation alone is 1/3 that of TCA [O]
OXIDATION OF PALMITATE
RECALL: [O] of Reducing Equivalents through eTC
1 mol NADH + H+ → 3 ATP (protons & e- → FMN)
1 mol FADH2 → 2 ATP (protons & e- → QH)
Thus, calculate efficiency of nrg capture in ATP from [O] of 1 mol of palmitate
(16:0) [256g]
1. Physiological fuel value of 256 g 16:0 = 256 x 38 KJ = 9728 KJ
2. Free nrg of hydrolysis of 1 mol ATP → ADP + Pi = 31.0 KJ
Therefore, [O] of 1 mol palmitate:
Activation - 2 ATP equivalents
7 “passes” thru β [O] [(7 x 2) + (7 x 3)] + 35 ATP equivalents
8 mols acetyl-CoA thru TCA (8 x 12) + 96 ATP equivalents
NET: 129 ATP equivalents
3. 3 times > [O] of 1 mol of glu (38 ATP)
4. Efficiency of nrg capture from 16:0 in ATP = 129 x 31.0 / 9728 x 100% = 40%
- FATTY ACID SYNTHESIS (LIPOGENESIS)
-endogenous synthesis (during “fed” state)
-main precursor for FAs syn is glu (CHO)
- also, excess nrg [CHO,AAs] → TG
FED: glu (1st glycogen) → acetyl-CoA + CO2 → FAs
SYNTHETIC PATHWAY
- cytosol (extramitochondrial)
1. starting material (acetyl-CoA) available
2. transport of acetyl-CoA from mitochondria to cytosol
oxaloacetate + acetyl-CoA → Citrate + CoASH
in cytosol: reconverted (citrate-cleavage enzyme)
3. carboxylation of acetyl-CoA →malonyl CoA
enzyme acetyl-CoA carboxylase - req biotin, ATP
- stimulated by ↑ insulin : glucagon
4. a. condensation of 2 C units (acetyl-CoA + malonyl CoA)
b. reduction to LC-SFAs (palmitate 16:0)
- multienzyme complex: FA synthetase
- Acyl Carrier Protein (ACP)
- source of reducing equivalents (NAPH + H+)
- from PPP in CHO metabolism
5. metabolic fate of palmityl CoA
- elongated (18:0), desaturated (18:1)
- form phosphatidic acid (NB in PL syn)
- used as nrg for liver (β [O] in mitochondria)
- esterified to form TG
e.g., in liver: glycerol 3-P [3-C backbone]
- TG exported on VLDL → tissues
- especially adipose
when is biotin used
acetyl caa-> malonyl coa (enzyme; acetyl coa carboxylase)
18:1
omega 9- olive oil
- BIOSYNTHESIS OF CHOLESTEROL
- endogenous synthesis (liver / intestinal mucosa)
- in cytosol of cell
SYNTHETIC PATHWAY (for more see text)
1. acetyl-CoA → acetoacetyl-CoA (thiolase) → 6C
β-OH-β-methylglutaryl CoA (HMG-CoA)
2. HMG-CoA → mevalonate → isoprene (5C) → squalene (30C)
↑
HMG-CoA reductase (NB “control” enzyme)
3. → cholesterol → bile acid (salts)
what is allosterically inhibited when cholesterol is high
HMG CoA reductase
some ppl dont have this
- FORMATION OF PHOSPHOLIPIDS
- endogenous synthesis (liver)
WHY?
1. provide for renewal/adjustment of the structural PLs in
its own membrane
2. to release PLs to other tissues via plasma LPs
3. to provide DG for syn of fats within liver
SYNTHETIC PATHWAY (for more see text)
1. glycerol or glycolysis (glu) → α-glycero-P (glycerol 3-P)
2. αGP + 2FA → phosphatidic acid → PLs & TGs
- FORMATION OF LIPOPROTEINS
for more see text
- LP formation major synthetic fn of liver
- LPs are PL-carrier ptn complexes:
- transport PLs to cell membranes (+ membranes within cell)
- LPs carriers of TG in blood
e.g., Liver Synthesis of Albumin
(albumin + lipid → blood transport → tissues)
what does albumion do
transports fat in the blood
LIPID METABOLISM: ADIPOSE
- adipose tissue can utilize circulating FAs
- cells have lipoptn lipase → free FAs from LPs
etc - FAs activated to CoA form & reesterified → TG
(3C backbone from glucose/glycogen)
adipocytes: - specialized cells for fat retention
- active cells:
1. FA synthesis
2. catabolic systems to release FAs
- hormone-sensitive lipase (HSL)
- lipolysis stimulated by ↓ insulin:glucagon
- FFAs (albumin) → tissue / organ
FAs found in adipose:
1. exogenous (of dietary origin)
- reflect FA composition of diet
2. endogenous (from syn from glu in liver, adipose)
- mainly palmitic acid
LIPID METABOLISM: MUSCLES
- capable of β-oxidation
- capable of ketone body oxidation
- β-OH-butyrate and acetoacetate - no capacity for FA or TG synthesis
“Role of Carnitine”:
- greater dependence on carnitine in
muscle for β-oxidation
LIPID METABOLISM: BRAIN
- neural tissue is rich in lipid (½ total mass)
- little TG
- most complex lipids: PLs, cholesterol, sphingolipids
1. FA and lipid synthesis from glu (or KBs) - FAs → complex lipids
- FAs do not → TG (storage fat)!!
2. cholesterol synthesis from acetyl CoA
3. no β-oxidation (nrg from glu)
glu → acetyl-CoA → TCA, sterol syn
4. neurotransmitter synthesis
glu → acetyl-CoA → acetylcholine
Genetic Diseases (Lipidoses): ↑ fat in nervous system
e.g., Tay-Sachs, Niemann-Pick disease, Gaucher’s disease
LIPID METABOLISM
OXIDATION
Many tissues (except obligate glucose users) can use
FFAs as a source of energy (through β-[O])
e.g., liver, heart (also [O] of KBs), skeletal muscle (also [O] of KBs)
LIPOGENESIS
Many tissues are capable of FA (TG) synthesis:
e.g., liver, adipose, lactating mammary gland, kidney, brain, lung
LIPID METABOLISM: PROLONGED FASTING
i.e.,3 days and onward
- liver glycogen stores depleted
- gluconeogenesis in liver (kidney?) sustains bld glu
- mobilization of adipose TG continues same as in
postabsorptive state (short fast) - liver begins to produce ketone bodies (KBs) as an
alternate fuel for brain, kidneys, heart / skeletal muscle
(replaces some glu used by brain / nerves)
KETOGENESIS (KB production):
production of β-OH-butyrate, acetoacetate, acetone
(true K) by liver from acetyl-CoA from FA [O]
1. depletion of malate (TCA) to support gluconeogenesis
→ ↓ oxaloacetate to support TCA [O]
2. rate of “delivery” of FFAs to liver remains high
- excess liver nrg (ATP) if FAs completely [O] (β and
TCA [O])
3. FAs → acetyl CoA → KB (liver) → blood → body
tissue
- production of an alternate nrg source
- brain + nervous tissue → spares glu
- muscle ptn → spares AAs (↓ proteolysis)
4. utilization of KBs by extrahepatic tissues
e.g., brain, nervous tis, kidneys, skeletal/heart muscle
- acetone expired in lungs (“acid” breath)
- all mitochondrial
β-OH butyrate → acetoacetate → 2 acetyl-CoA (thru TCAcycle)
→ CO2 + H2O + ATP + etc
malate maintains
blood glucose levels
LIPID METABOLISM: PROLONGED FASTING
KETOSIS:
- KB in blood (ketonemia) and urine (ketonuria) > normal
- β-OH-butyrate and acetoacetate are acids → ↓ bld pH
- normally not a problem
e. g., mild starvation, low CHO diets - can be problem in uncontrolled diabetes
- excess KB excretion in urine depletes alkali reserve
e. g., bicarbonate, potassium, ammonium ions
BLOOD LIPIDS
LP classes and composition (1-5 are globulins)
- chylomicra - ↑↑ fat ↓ increasing densities
- VLDL - ↑ fat (TG)
- IDL – short lived
- LDL - ↑ chol
- HDL - ↑ PLs
- VHDL - albumin, ↓ fat, some FAs
LIPID METABOLISM
OXIDATION
Many tissues (except obligate glucose users) can use
FFAs as a source of energy (through β-[O])
e.g., liver, heart (also [O] of KBs), skeletal muscle (also [O] of KBs)
LIPOGENESIS
Many tissues are capable of FA (TG) synthesis:
e.g., liver, adipose, lactating mammary gland, kidney, brain, lung
LIPID METABOLISM: PROLONGED FASTING
i.e.,3 days and onward
- liver glycogen stores depleted
- gluconeogenesis in liver (kidney?) sustains bld glu
- mobilization of adipose TG continues same as in
postabsorptive state (short fast) - liver begins to produce ketone bodies (KBs) as an
alternate fuel for brain, kidneys, heart / skeletal muscle
(replaces some glu used by brain / nerves)
KETOGENESIS (KB production):
production of β-OH-butyrate, acetoacetate, acetone
(true K) by liver from acetyl-CoA from FA [O]
1. depletion of malate (TCA) to support gluconeogenesis
→ ↓ oxaloacetate to support TCA [O]
2. rate of “delivery” of FFAs to liver remains high
- excess liver nrg (ATP) if FAs completely [O] (β and
TCA [O])
3. FAs → acetyl CoA → KB (liver) → blood → body
tissue
- production of an alternate nrg source
- brain + nervous tissue → spares glu
- muscle ptn → spares AAs (↓ proteolysis)
4. utilization of KBs by extrahepatic tissues
e.g., brain, nervous tis, kidneys, skeletal/heart muscle
- acetone expired in lungs (“acid” breath)
- all mitochondrial
β-OH butyrate → acetoacetate → 2 acetyl-CoA (thru TCAcycle)
→ CO2 + H2O + ATP + etc
malate maintains
blood glucose levels
LIPID METABOLISM: PROLONGED FASTING
KETOSIS:
- KB in blood (ketonemia) and urine (ketonuria) > normal
- β-OH-butyrate and acetoacetate are acids → ↓ bld pH
- normally not a problem
e. g., mild starvation, low CHO diets - can be problem in uncontrolled diabetes
- excess KB excretion in urine depletes alkali reserve
e. g., bicarbonate, potassium, ammonium ions
BLOOD LIPIDS
LP classes and composition (1-5 are globulins)
- chylomicra - ↑↑ fat ↓ increasing densities
- VLDL - ↑ fat (TG)
- IDL – short lived
- LDL - ↑ chol
- HDL - ↑ PLs
- VHDL - albumin, ↓ fat, some FAs
BLOOD LIPIDS
Transport Mechanisms:
- Chylomicra : carry diet fats (TG) absorbed from gut → adipose
(+ tissues with lipoptn lipase) - VLDL: carry endogenous TGs (ie, liver) → adipose (+ other tissues)
- LDL: cholesterol → peripheral tissue
- HDL: - aids (as UFA donor) in conversion of
chol → chol ester
- tissue chol → liver → bile excretion - VHDL: - LPs after lipids removed → liver (reutilized)
- FAs from adipose → albumin bound, FAs → tissue
CONCERNS ABOUT LIPIDS
- Lipid deposition in atherosclerosis (CHD)
- multi-factor disease
- risks: genetic
environmental – smoking
- diabetes
- hypertension
- lack of exercise
- gross obesity
- ↑ blood cholesterol
- The hyperlipidemias (hyperlipoproteinemia)
Inherited (inborn errors of metabolism)
a. Type I: absence of lipoptn lipase (breaks tg bonds so that they can be delivered to various tissues- without enzyme would perscribe diet iwht medium and short chain fatty acids so that they dont have to go in a chylomicron)
b. Type II: ↑↑↑ LDL (cholesterol)
c. Type III: ↑ cholesterol & ↑ TG
d. Type IV: ↑ VLDL (TG)
Secondary hyperlipidemias
Environmental Factors: e.g., ↑ calories, ↑ EOH
LIPID METABOLISM
OXIDATION
Many tissues (except obligate glucose users) can use
FFAs as a source of energy (through β-[O])
e.g., liver, heart (also [O] of KBs), skeletal muscle (also [O] of KBs)
LIPOGENESIS
Many tissues are capable of FA (TG) synthesis:
e.g., liver, adipose, lactating mammary gland, kidney, brain, lung
LIPID METABOLISM: PROLONGED FASTING
i.e.,3 days and onward
- liver glycogen stores depleted
- gluconeogenesis in liver (kidney?) sustains bld glu
- mobilization of adipose TG continues same as in
postabsorptive state (short fast) - liver begins to produce ketone bodies (KBs) as an
alternate fuel for brain, kidneys, heart / skeletal muscle
(replaces some glu used by brain / nerves)
KETOGENESIS (KB production):
production of β-OH-butyrate, acetoacetate, acetone
(true K) by liver from acetyl-CoA from FA [O]
1. depletion of malate (TCA) to support gluconeogenesis
→ ↓ oxaloacetate to support TCA [O]
2. rate of “delivery” of FFAs to liver remains high
- excess liver nrg (ATP) if FAs completely [O] (β and
TCA [O])
3. FAs → acetyl CoA → KB (liver) → blood → body
tissue
- production of an alternate nrg source
- brain + nervous tissue → spares glu
- muscle ptn → spares AAs (↓ proteolysis)
4. utilization of KBs by extrahepatic tissues
e.g., brain, nervous tis, kidneys, skeletal/heart muscle
- acetone expired in lungs (“acid” breath)
- all mitochondrial
β-OH butyrate → acetoacetate → 2 acetyl-CoA (thru TCAcycle)
→ CO2 + H2O + ATP + etc
malate maintains
blood glucose levels
LIPID METABOLISM: PROLONGED FASTING
KETOSIS:
- KB in blood (ketonemia) and urine (ketonuria) > normal
- β-OH-butyrate and acetoacetate are acids → ↓ bld pH
- normally not a problem
e. g., mild starvation, low CHO diets - can be problem in uncontrolled diabetes
- excess KB excretion in urine depletes alkali reserve
e. g., bicarbonate, potassium, ammonium ions
BLOOD LIPIDS
LP classes and composition (1-5 are globulins)
- chylomicra - ↑↑ fat ↓ increasing densities
- VLDL - ↑ fat (TG)
- IDL – short lived
- LDL - ↑ chol
- HDL - ↑ PLs
- VHDL - albumin, ↓ fat, some FAs
BLOOD LIPIDS
Transport Mechanisms:
- Chylomicra : carry diet fats (TG) absorbed from gut → adipose
(+ tissues with lipoptn lipase) - VLDL: carry endogenous TGs (ie, liver) → adipose (+ other tissues)
- LDL: cholesterol → peripheral tissue
- HDL: - aids (as UFA donor) in conversion of
chol → chol ester
- tissue chol → liver → bile excretion - VHDL: - LPs after lipids removed → liver (reutilized)
- FAs from adipose → albumin bound, FAs → tissue
CONCERNS ABOUT LIPIDS
- Lipid deposition in atherosclerosis (CHD)
- multi-factor disease
- risks: genetic
environmental – smoking
- diabetes
- hypertension
- lack of exercise
- gross obesity
- ↑ blood cholesterol
- The hyperlipidemias (hyperlipoproteinemia)
Inherited (inborn errors of metabolism)
a. Type I: absence of lipoptn lipase (breaks tg bonds so that they can be delivered to various tissues- without enzyme would perscribe diet iwht medium and short chain fatty acids so that they dont have to go in a chylomicron)
b. Type II: ↑↑↑ LDL (cholesterol)
c. Type III: ↑ cholesterol & ↑ TG
d. Type IV: ↑ VLDL (TG)
Secondary hyperlipidemias
Environmental Factors: e.g., ↑ calories, ↑ EOH
know 1 and 2
Dietary Fats: Total Fat and Fatty Acids
Total Fat
AI and RDA not set because insufficient data to
determine a defined level of fat intake at which risk
of inadequacy or prevention of chronic disease
occurs
UL not set because no defined intake level at which
an adverse event occurs
AMDR =
30 - 40% of nrg for children (1-3 y)
25 - 35% of nrg for children (4-18 y)
20 - 35% of nrg for adults (old RNIs 30%)
Saturated Fat (SFA) & Trans Fat
AI and RDA not set because insufficient data to
determine a defined level of SFA or TFA intake at which
prevention of chronic disease occurs
UL not set, however, positive linear between SFA and
LDL-C and increase risk of CHD could be basis of UL of
zero
Not possible because all fats contain some SFA
Recommendation that SFA and TFA be as low as
possible
transfat has to be removed from all products - except for the trans in dairy, meat
Monounsaturated Fat (oleic acid 18:1n9)
AI not set because MUFA synthesized in the body
UL not set due to insufficient evidence
n-6 PUFA (linoleic acid 18:2n6)
AI set for all age/sex groups (range 11 - 17 g/d in
adult)
UL not set due to insufficient evidence
AMDR = 5 – 10% of nrg
n-3 PUFA (ALA 18:3n3, EPA 20:5n3, DHA 22;6n3)
AI set for all age/sex groups (range 1.1 - 1.6 g/d in adult)
Mostly ALA, EPA & DHA can contribute up to 10% of n-3 intake
UL not set due to insufficient evidence
AMDR = 0.6 – 1.2% of nrg
LIPID METABOLISM
OXIDATION
Many tissues (except obligate glucose users) can use
FFAs as a source of energy (through β-[O])
e.g., liver, heart (also [O] of KBs), skeletal muscle (also [O] of KBs)
LIPOGENESIS
Many tissues are capable of FA (TG) synthesis:
e.g., liver, adipose, lactating mammary gland, kidney, brain, lung
LIPID METABOLISM: PROLONGED FASTING
i.e.,3 days and onward
- liver glycogen stores depleted
- gluconeogenesis in liver (kidney?) sustains bld glu
- mobilization of adipose TG continues same as in
postabsorptive state (short fast) - liver begins to produce ketone bodies (KBs) as an
alternate fuel for brain, kidneys, heart / skeletal muscle
(replaces some glu used by brain / nerves)
KETOGENESIS (KB production):
production of β-OH-butyrate, acetoacetate, acetone
(true K) by liver from acetyl-CoA from FA [O]
1. depletion of malate (TCA) to support gluconeogenesis
→ ↓ oxaloacetate to support TCA [O]
2. rate of “delivery” of FFAs to liver remains high
- excess liver nrg (ATP) if FAs completely [O] (β and
TCA [O])
3. FAs → acetyl CoA → KB (liver) → blood → body
tissue
- production of an alternate nrg source
- brain + nervous tissue → spares glu
- muscle ptn → spares AAs (↓ proteolysis)
4. utilization of KBs by extrahepatic tissues
e.g., brain, nervous tis, kidneys, skeletal/heart muscle
- acetone expired in lungs (“acid” breath)
- all mitochondrial
β-OH butyrate → acetoacetate → 2 acetyl-CoA (thru TCAcycle)
→ CO2 + H2O + ATP + etc
malate maintains
blood glucose levels
LIPID METABOLISM: PROLONGED FASTING
KETOSIS:
- KB in blood (ketonemia) and urine (ketonuria) > normal
- β-OH-butyrate and acetoacetate are acids → ↓ bld pH
- normally not a problem
e. g., mild starvation, low CHO diets - can be problem in uncontrolled diabetes
- excess KB excretion in urine depletes alkali reserve
e. g., bicarbonate, potassium, ammonium ions
BLOOD LIPIDS
LP classes and composition (1-5 are globulins)
- chylomicra - ↑↑ fat ↓ increasing densities
- VLDL - ↑ fat (TG)
- IDL – short lived
- LDL - ↑ chol
- HDL - ↑ PLs
- VHDL - albumin, ↓ fat, some FAs
BLOOD LIPIDS
Transport Mechanisms:
- Chylomicra : carry diet fats (TG) absorbed from gut → adipose
(+ tissues with lipoptn lipase) - VLDL: carry endogenous TGs (ie, liver) → adipose (+ other tissues)
- LDL: cholesterol → peripheral tissue
- HDL: - aids (as UFA donor) in conversion of
chol → chol ester
- tissue chol → liver → bile excretion - VHDL: - LPs after lipids removed → liver (reutilized)
- FAs from adipose → albumin bound, FAs → tissue
CONCERNS ABOUT LIPIDS
- Lipid deposition in atherosclerosis (CHD)
- multi-factor disease
- risks: genetic
environmental – smoking
- diabetes
- hypertension
- lack of exercise
- gross obesity
- ↑ blood cholesterol
- The hyperlipidemias (hyperlipoproteinemia)
Inherited (inborn errors of metabolism)
a. Type I: absence of lipoptn lipase (breaks tg bonds so that they can be delivered to various tissues- without enzyme would perscribe diet iwht medium and short chain fatty acids so that they dont have to go in a chylomicron)
b. Type II: ↑↑↑ LDL (cholesterol)
c. Type III: ↑ cholesterol & ↑ TG
d. Type IV: ↑ VLDL (TG)
Secondary hyperlipidemias
Environmental Factors: e.g., ↑ calories, ↑ EOH
know 1 and 2
Dietary Fats: Total Fat and Fatty Acids
Total Fat
AI and RDA not set because insufficient data to
determine a defined level of fat intake at which risk
of inadequacy or prevention of chronic disease
occurs
UL not set because no defined intake level at which
an adverse event occurs
AMDR =
30 - 40% of nrg for children (1-3 y)
25 - 35% of nrg for children (4-18 y)
20 - 35% of nrg for adults (old RNIs 30%)
Saturated Fat (SFA) & Trans Fat
AI and RDA not set because insufficient data to
determine a defined level of SFA or TFA intake at which
prevention of chronic disease occurs
UL not set, however, positive linear between SFA and
LDL-C and increase risk of CHD could be basis of UL of
zero
Not possible because all fats contain some SFA
Recommendation that SFA and TFA be as low as
possible
transfat has to be removed from all products - except for the trans in dairy, meat
Monounsaturated Fat (oleic acid 18:1n9)
AI not set because MUFA synthesized in the body
UL not set due to insufficient evidence
n-6 PUFA (linoleic acid 18:2n6)
AI set for all age/sex groups (range 11 - 17 g/d in
adult)
UL not set due to insufficient evidence
AMDR = 5 – 10% of nrg
n-3 PUFA (ALA 18:3n3, EPA 20:5n3, DHA 22;6n3)
AI set for all age/sex groups (range 1.1 - 1.6 g/d in adult)
Mostly ALA, EPA & DHA can contribute up to 10% of n-3 intake
UL not set due to insufficient evidence
AMDR = 0.6 – 1.2% of nrg
Dietary Cholesterol
AI and RDA not set since all tissues synthesize sufficient
amounts of cholesterol
UL not set, however, recommended that cholesterol consumption
be as low as possible while consuming a nutritionally adequate
diet
Nutritional Value of Eggs
High Quality Protein Vitamins Minerals & Trace Elements Essential Fatty Acids Low in Saturated Fats Other Bioactive Compounds
harvard said that fat is bad
Current State of Knowledge
Saturated fats and trans-fatty acids increase LDL cholesterol
Dietary cholesterol has much lower impact on total and LDL
serum cholesterol levels than earlier predictions
Need to consider LDL:HDL ratio
Prospective study by Hu et al. (1999) reported no association
with egg consumption and cardiovascular disease in healthy
adults
Exception: Diabetic subjects
Do we need to limit egg intake in general population?
LIPID METABOLISM
OXIDATION
Many tissues (except obligate glucose users) can use
FFAs as a source of energy (through β-[O])
e.g., liver, heart (also [O] of KBs), skeletal muscle (also [O] of KBs)
LIPOGENESIS
Many tissues are capable of FA (TG) synthesis:
e.g., liver, adipose, lactating mammary gland, kidney, brain, lung
LIPID METABOLISM: PROLONGED FASTING
i.e.,3 days and onward
- liver glycogen stores depleted
- gluconeogenesis in liver (kidney?) sustains bld glu
- mobilization of adipose TG continues same as in
postabsorptive state (short fast) - liver begins to produce ketone bodies (KBs) as an
alternate fuel for brain, kidneys, heart / skeletal muscle
(replaces some glu used by brain / nerves)
KETOGENESIS (KB production):
production of β-OH-butyrate, acetoacetate, acetone
(true K) by liver from acetyl-CoA from FA [O]
1. depletion of malate (TCA) to support gluconeogenesis
→ ↓ oxaloacetate to support TCA [O]
2. rate of “delivery” of FFAs to liver remains high
- excess liver nrg (ATP) if FAs completely [O] (β and
TCA [O])
3. FAs → acetyl CoA → KB (liver) → blood → body
tissue
- production of an alternate nrg source
- brain + nervous tissue → spares glu
- muscle ptn → spares AAs (↓ proteolysis)
4. utilization of KBs by extrahepatic tissues
e.g., brain, nervous tis, kidneys, skeletal/heart muscle
- acetone expired in lungs (“acid” breath)
- all mitochondrial
β-OH butyrate → acetoacetate → 2 acetyl-CoA (thru TCAcycle)
→ CO2 + H2O + ATP + etc
malate maintains
blood glucose levels
LIPID METABOLISM: PROLONGED FASTING
KETOSIS:
- KB in blood (ketonemia) and urine (ketonuria) > normal
- β-OH-butyrate and acetoacetate are acids → ↓ bld pH
- normally not a problem
e. g., mild starvation, low CHO diets - can be problem in uncontrolled diabetes
- excess KB excretion in urine depletes alkali reserve
e. g., bicarbonate, potassium, ammonium ions
BLOOD LIPIDS
LP classes and composition (1-5 are globulins)
- chylomicra - ↑↑ fat ↓ increasing densities
- VLDL - ↑ fat (TG)
- IDL – short lived
- LDL - ↑ chol
- HDL - ↑ PLs
- VHDL - albumin, ↓ fat, some FAs
BLOOD LIPIDS
Transport Mechanisms:
- Chylomicra : carry diet fats (TG) absorbed from gut → adipose
(+ tissues with lipoptn lipase) - VLDL: carry endogenous TGs (ie, liver) → adipose (+ other tissues)
- LDL: cholesterol → peripheral tissue
- HDL: - aids (as UFA donor) in conversion of
chol → chol ester
- tissue chol → liver → bile excretion - VHDL: - LPs after lipids removed → liver (reutilized)
- FAs from adipose → albumin bound, FAs → tissue
CONCERNS ABOUT LIPIDS
- Lipid deposition in atherosclerosis (CHD)
- multi-factor disease
- risks: genetic
environmental – smoking
- diabetes
- hypertension
- lack of exercise
- gross obesity
- ↑ blood cholesterol
- The hyperlipidemias (hyperlipoproteinemia)
Inherited (inborn errors of metabolism)
a. Type I: absence of lipoptn lipase (breaks tg bonds so that they can be delivered to various tissues- without enzyme would perscribe diet iwht medium and short chain fatty acids so that they dont have to go in a chylomicron)
b. Type II: ↑↑↑ LDL (cholesterol)
c. Type III: ↑ cholesterol & ↑ TG
d. Type IV: ↑ VLDL (TG)
Secondary hyperlipidemias
Environmental Factors: e.g., ↑ calories, ↑ EOH
know 1 and 2
Dietary Fats: Total Fat and Fatty Acids
Total Fat
AI and RDA not set because insufficient data to
determine a defined level of fat intake at which risk
of inadequacy or prevention of chronic disease
occurs
UL not set because no defined intake level at which
an adverse event occurs
AMDR =
30 - 40% of nrg for children (1-3 y)
25 - 35% of nrg for children (4-18 y)
20 - 35% of nrg for adults (old RNIs 30%)
Saturated Fat (SFA) & Trans Fat
AI and RDA not set because insufficient data to
determine a defined level of SFA or TFA intake at which
prevention of chronic disease occurs
UL not set, however, positive linear between SFA and
LDL-C and increase risk of CHD could be basis of UL of
zero
Not possible because all fats contain some SFA
Recommendation that SFA and TFA be as low as
possible
transfat has to be removed from all products - except for the trans in dairy, meat
Monounsaturated Fat (oleic acid 18:1n9)
AI not set because MUFA synthesized in the body
UL not set due to insufficient evidence
n-6 PUFA (linoleic acid 18:2n6)
AI set for all age/sex groups (range 11 - 17 g/d in
adult)
UL not set due to insufficient evidence
AMDR = 5 – 10% of nrg
n-3 PUFA (ALA 18:3n3, EPA 20:5n3, DHA 22;6n3)
AI set for all age/sex groups (range 1.1 - 1.6 g/d in adult)
Mostly ALA, EPA & DHA can contribute up to 10% of n-3 intake
UL not set due to insufficient evidence
AMDR = 0.6 – 1.2% of nrg
Dietary Cholesterol
AI and RDA not set since all tissues synthesize sufficient
amounts of cholesterol
UL not set, however, recommended that cholesterol consumption
be as low as possible while consuming a nutritionally adequate
diet
Nutritional Value of Eggs
High Quality Protein Vitamins Minerals & Trace Elements Essential Fatty Acids Low in Saturated Fats Other Bioactive Compounds
harvard said that fat is bad
Current State of Knowledge
Saturated fats and trans-fatty acids increase LDL cholesterol
Dietary cholesterol has much lower impact on total and LDL
serum cholesterol levels than earlier predictions
Need to consider LDL:HDL ratio
Prospective study by Hu et al. (1999) reported no association
with egg consumption and cardiovascular disease in healthy
adults
Exception: Diabetic subjects
Do we need to limit egg intake in general population?
never tested to see if eggs increase serum cholesterol
chapter 8 integration of metabolism-
some might have good review slides
t and f with justification, 10 multiple choice, describe question in nutrition context
short answer, more specific in fat
will be some choice
j
