Virginia Tech Dr. Anderson HNFE 4025 Exam 2

fatty acids, glycerides, non-glyceride lipids, lipid carriers

what are the 4 categories of lipids?

carrier

Fatty Acids

- saturated = no double bonds

- unsaturated = one or more double bonds

- monounsaturated (MUFA) = one double bond

- polyunsaturated (PUFA) = two more double bonds

- free FAs don't have a glycerol backbone

- can't travel in blood as free FAs, must have a _______________

cis

Fatty Acid Structure

- carboxylic (-COOH) end (hydrophilic) and methyl (-CH3) end (hydrophobic)

- unsaturated FAs are typically in ______ configuration → kinking of chain

delta (Δ), omega (ω)

Fatty Acid Nomenclature

what are the two shorthand notation systems?

Delta

Fatty Acid Nomenclature

__________ system

- denotes chain length and number of double bonds

- lists position of all double bonds

methyl

Fatty Acid Nomenclature

Omega system

- denotes chain length and number of double bonds

- gives position of first double bond from the ___________ end

linoleic acid

Common Polyunsaturated Fatty Acids (PUFAs)

____________________ is an essential FA that is a ω6

linolenic acid

Common Polyunsaturated Fatty Acids (PUFAs)

____________________ is an essential FA that is a ω3

EPA and DHA

Essential vs. Nonessential FAs

non-essential ω3 fatty acids made from linolenic and linoleic acid

plant

Essential FAs

- unsaturated FAs that cannot be synthesized in animals cells because we lack the enzymes to insert double bonds beyond carbon 9

- acquired from __________ sources

α-linolenic acid

Omega 3 FAs

- found in cold water fish (salmon, tuna, halibut), other marine life such as algae and krill, certain plants (purslane, hemp, flax), and nut oils

- the body converts _____________________ to EPA and DHA, the two types of omega-3 fatty acids more readily used by the body

anti-inflammatory, pro-inflammatory

Essential FAs

omega-3s are considered (anti-inflammatory/pro-inflammatory) while omega-6s are considered (anti-inflammatory/pro-inflammatory)

😊

ω-6 to ω-3 ratio is important

- ω-3 FAs help reduce inflammation, and most ω-6 FAs tend to promote inflammation

- a healthy diet should have a ratio (ω-6:ω-3) somewhere between 2:1 and 5:1

- the typical American diet is between 10:1 and 30:1

triglycerides

Glycerolipids (Acylglycerols)

- mono-, di-, and tri-esters of glycerol and FAs

- most FAs in nature are found as glycerolipids (mainly TAG)

- triacylglycerols is a synonym for _________________

solid

Physical Properties of TAGs

- more saturated fatty acids act to increase the melting point, making them __________ at room temperature

- more unsaturated or short chain length fatty acids lowers the melting point

sterol

type of lipid characterized by a 4-ring core structure; cholesterol is the only one made by humans

cholesteryl ester

Sterols

When we add a FA to the OH group of cholesterol, we get ____________________

glycerol + 2 FAs + phosphate group

Phospholipids

what is the structure of a phospholipid?

choline

Phospholipids

typically on phosphate group is a head group, usually _____________

glycerophosphatides, sphingophosphatides

Phospholipids

- many are derivatives of phosphatidic acid (phosphatidate)

- classified into what two categories?

glycerol

Phospholipids

glycerophosphatides have a ____________ core structure

amino alcohol

Phospholipids

sphingophosphatides have a ________ ____________ core structure

phosphatidylcholine

Phospholipids

_______________________ is a phospholipid with a choline head group

protein

Lipoproteins

- made up of a phospholipid shell with some cholesterol and proteins (apolipoproteins) inserted throughout

- on the inside, lipoproteins transport TAGs, cholesterol, FAs, & fat-soluble vitamins

- the more __________, the more dense it is: HDL has the most __________ and is the smallest

same answer

small intestine

Lipoproteins

Chylomicrons

- biggest lipoprotein

- formed where?

- primarily carries TAGs to be stored in adipose tissue

liver

Lipoproteins

VLDLs

- second biggest

- has the same job as chylomicrons: to drop off triglycerides

- formed in the __________

- primarily carries TAGs to be stored in adipose tissue

cholesterol

Lipoproteins

LDLs

- formed in the liver

- formed after VLDLs have dropped off all their TAGs

- primarily carries ________________ to the tissues

disposal (degradation)

Lipoproteins

HDLs

- smallest lipoprotein

- formed in the liver

- primary carries cholesterol away from tissues for ____________

triglycerides

Lipoproteins

what makes up the majority of chylomicrons?

triglycerides

Lipoproteins

what makes up the majority of VLDLs?

cholesterol

Lipoproteins

what makes up the majority LDLs?

proteins

Lipoproteins

what makes up the majority of HDLs?

fed, fasted

Lipoproteins

chylomicrons are the major lipoprotein found in a ___________ state, while VLDLs and LDLs are the majority lipoprotein found in a _________ state

fasted

Fatty Acid Metabolism

working more when in __________ state

ectopic

Synthesis and Storage of Lipids

if we have high circulating TAGs in the blood, we might start storing TAGs in places we shouldn't, which is called __________ storage, causing fatty liver, a fatty heart, and TAGs in skeletal muscle

lipolysis

Fatty Acid Oxidation

the process of liberating FFA from TAGs

CoA

Fatty Acid Oxidation

fatty acids come into skeletal muscle and we have to activate them by adding a ______ to be able to get the FA into the mitochondria

inside the mitochondria, we have beta-oxidation

acetyl CoA synthetase

Fatty Acid Activation

- long-chain fatty acids are transported into the cell via FA transporters

- once in the cell, the FA must be "activated" to be able to enter the mitochondria, where FA oxidation takes place

- what enzyme? adds a CoA at the expense of 2 ATP (ATP → AMP)

CoA

Carnitine Shuttle

- made up of 2 enzymes and 1 transport protein

- CoA molecules are not permeable to the inner mitochondrial membrane

(1) CPT1 enzyme in the intermembrane space takes off the CoA from the FA and adds a carnitine

(2) now the FA-carnitine can enter via Carnitine Acylcarnitine Translocase (SLC25A20) in exchange for carnitine (an antiport)

(3) once in the matrix, CPT II enzyme swaps the carnitine for a _________ to remake the FA-CoA

(4) the FA-CoA can now enter beta oxidation and be catabolized

1 acetyl CoA, 1 NADH, 1 FADH2

Beta-Oxidation

- occurs in the mitochondrial matrix

- a cycle of 4 enzymatic steps that cleaves a FA 2 carbons at a time

- what are the products from 1 turn of beta-oxidation?

106 (2 ATP invested to produce the FA-CoA via Acetyl CoA Synthetase in the cytoplasm)

ATP Production from B-oxidation of Palmitate (16C)

(1) 16C = 8 acetyl-CoA → each acetyl-CoA enters TCA cycle and produces 1 FADH2 (1.5), 3 NADH (7.5), 1 GTP (1) = 10 ATP → 10x8 = 80 ATP

(2) 16 carbons = 7 cycles of beta-oxidation → each cycle produces 1 FADH2 (1.5) & 1 NADH (2.5) = 4 ATP → 7x4 = 28 ATP

80 ATP + 28 ATP = 108 ATP per 1 palmitate FA

net = _____ ATP

1.5

ATP Production from an Unsaturated FA

for every double bond in an unsaturated FA, you need to subtract _____ ATP from the total ATP yield (due to a loss of a FADH2 produced)

succinyl CoA

ATP Production from an Odd-Chained FA

- beta oxidation proceeds as normal until the last 5 carbons are left

- these are split into an acetyl CoA and a 3-C propionyl CoA

- propionyl CoA can be converted to _________________ through several steps

- but the first step requires 1 ATP and succinyl CoA enters into the TCA cycle skipping the first 3 enzymatic steps, thereby missing out on 2 NADH being produced (5 ATP), but still generates 5 ATP (1 NADH, 1 FADH2, 1 GTP

100

ATP Production from an Odd-Chained FA

Example from 17 carbon Margaric Acid

- 17C → 7 acetyl-CoA produced x 10 ATP = 70 ATP

- 7 cycles of beta-oxidation x 4 ATP = 28 ATP

- 1 succinyl-CoA → 5 ATP

- minus 1 ATP for conversion from propionyl CoA

- minus 2 ATP for activation of FA (adding CoA)

- net total = _______ ATP

20

Amino Acids

____ AAs are used to make protein in our body

codon

Amino Acids

- each 3 nucleotides in mRNA code for an amino acid, this is called a __________

- tRNA brings the correct amino acid during translation by complementarily matching its anticodon to the correct codon

methionine

Codons

the start codon AUG also codes for ___________

L,D

Amino Acids

only ___-amino acids are used to make proteins in our bodies; ___-amino acids are rare in nature

electrical

Amino Acid Classification

(1) net __________ charge: at physiologic pH, is it 0, +, or -

the side chain (R group)

Amino Acid Classification

(2) Structure: what? makes each amino acid unique

hydrophobic or hydrophilic

Amino Acid Classification

(3) Polarity: the polarity of the R group determines the degree of interaction with water, ________________ or _______________

gluconeogenic or ketogenic

Amino Acid Classification

(4) Carbon skeleton fate: __________________ or ______________

Essentiality

Amino Acid Classification

(5) _______________: Dietary requirement

•A central (α) carbon

•At least 1 amino group (-NH2)

•At least 1 carboxyl group (-COOH)

•A side chain (R group)

what is the structure of a AA?

donate

Effect of pH on Amino Acids

amino acids in proteins (donate/accept) hydrogens when the pH is too high (basic)

amphoteric

amino acids are ______________ = they act as either acids or bases

-COOH, -NH3+

AAs are amphoteric

Acids are _________ and __________

- each of these have protons to donate

Bases are -COO- and -NH2

- each of these can accept a proton to become the acid form

zwitterions

Amino Acid Net Electrical Charge

At physiologic pH, AAs are predominately dipolar ions or _______________ where the amino group is protonated with a positive charge and the carboxyl group is dissociated with a negative charge

polypeptides

AA Classification by Structure

- the side chain (R group) has a distinctive characteristic

- gives structure and function to ________________

- determines whether a given amino acid can be synthesized or must be ingested

- determines specific pathways for metabolism

- 7 structural groups: aliphatic, containing a hydroxyl group, containing an aromatic ring, containing sulfur, acidic (and their amides), basic, imino acid

just has carbons and hydrogens, has no net charge at physiological pH

AA Classification by Structure

what does aliphatic mean?

phosphorylation

AA Classification by Structure

AAs with a hydroxyl group

- polar, dissociable side group

- hydroxyl group = point of _________________ for proteins

aromatic

AA Classification by Structure

AAs with a ____________ ring: aid in selective recognition at binding sites

imino

AA Classification by Structure

proline is the example of a ___________ AA: rigid structure allows it to help with protein (collagen) structure

polarity

AA Classification

the tendency of an AA to interact with H2O

outside

AA Classifications

Polarity of AA

- neutral: hydrogen bonds with H20

- charged: forms salt bridges and interacts with electrolytes

- found on ___________ of proteins, since they interact with water

phobic

AA Classifications

Polarity of AA: nonpolar AAs are hydro________

ketogenic

Classification By Fate of their Carbons

(1) ___________ AAs: cannot be converted to glucose, only via acetyl-CoA or acetoacetate (2 acetyl-CoA together) = building block of ketones

leucine and lysine

Classification By Fate of their Carbons

what are the only 2 ketogenic AAs?

glucogenic

Classification By Fate of their Carbons

the other 18 AAs are _______________ = all of their carbon skeletons can be converted to glucose

acetyl-CoA

Classification By Fate of their Carbons

some AAs are both glucogenic and ketogenic = part of carbon skeleton converted to glucose and the remainder to __________________

alanine

Classification By Fate of their Carbons

what is the most common AA that gets used to make glucose via being converted to pyruvate?

Phenylalanine

Valine

Tryptophan

Threonine

Isoleucine

Methionine

Histidine

Arginine (conditionally essential)

Leucine

Lysine

Essential AAs

what are the 9 essential AAs?

arginine

what AA is conditionally essential (essential for infants)?

conditionally essential

_____________ AA necessity depends on the developmental stage, health status or disease state of an individual; these can generally be synthesized, provided there are adequate amounts of their precursors

valine, leucine, isoleucine

AA Classification by Structure

what are the 3 branched chain AAs?

protein

Branched Chain AAs (BCAAs)

- valine, leucine, isoleucine

- the most common essential AAs in body __________

- mostly catabolized in skeletal muscle (compared to liver)

urea

Metabolism of AAs

proteins → AAs → amino group and carbon skeleton

amino group → _________ ammonia → excretion by kidney (mostly) and by intestinal tract

energy

Metabolism of AAs

proteins → AAs → amino group and carbon skeleton

carbon skeleton → glucose (via gluconeogenesis) and/or ketone bodies, _________ + CO2, or fatty acids (has to be a lot of AA metabolism to start making FAs)

fed

protein synthesis will dominate in a ________ state

fasted

In what state is protein/amino acid degradation

going to predominate?

creatinine

AA Components Have Different Fats

amino acid nitrogen will ultimately appear in the urine as:

(1) nitrogen atoms in urea (mostly)

(2) ____________ (from creatine)

(3) uric acid (from nucleic acid bases)

(4) NH4+

transamination, deamination

to remove the amino group from an AA, what are the 2 ways?

transamination

transfer of the amino group from an AA to an a-keto acid, making a new AA and a keto-acid

deamination

removal of the amino group - producing ammonium (NH4+)

liver

Urea Cycle

- ammonium is very toxic

- the urea cycle, in the _________, converts ammonium to urea, which is then transported to the kidneys where it is secreted

not on exam 2

glutamine

Urea Cycle

______________ synthesis is a backup system: glutamate + NH4+ → glutamine, which can then enter the blood

found in perivenous hepatocytes

not on exam 2

liver, partially in cytoplasm and partially in mitochondria of periportal hepatocytes

Urea Cycle

where does urea cycle occur?

not on exam 2

postprandial

Metabolism Under Fed Conditions

________________ metabolism refers to the period of time after meal when food is being digestion, distributed and transported, and metabolized; ranges from 4-6 hours following consumption of a meal

small intestine

Macronutrient Digestion

- to break down proteins → AAs, carbs → simple monosaccharides, lipids (TAGs, cholesterol esters, phospholipids) → smaller absorbable lipids

- most digestion occurs in ________ _________________ in the lumen and at the brush border

salivary α-amylase

CHO Digestion In Mouth

- polysaccharide digestion begins in the mouth

- this enzyme hydrolyses alpha-1,4-glycosidic bonds

isomaltase

CHO Digestion In Mouth

this enzyme breaks down α-1,6-glycosidic bonds

submandibular, parotid, sublingual

what are the 3 pairs of salivary glands that make saliva?

submandibular, parotid

Salivary Glands

what salivary glands produce salivary amylase?

no (low pH of gastric juice in the stomach inhibits salivary α-amylase activity)

is there CHO digestion in the stomach?

maltose (can), sucrose (cannot), lactose (cannot)

what are the 3 disaccharides and which of them can α-amylase digest?

lingual lipase

Lipid Digestion in the Mouth

this enzyme is secreted from the serous gland beneath the tongue and cleaves the ester bond at the carbon 3 position of TAGs → 1,2-diacylglycerol and free FAs; overall has a minor contribution to digestion

protein

Digestion in the Mouth

Other than chewing, no digestion of ____________ occurs in the mouth

gastric lipase

Lipid Digestion in the Stomach

this enzyme is released from gastric mucosa and attacks TAGs → 1,3-DAGs and free FAs; important for infants

emulsification

Lipid Digestion in the Stomach

lipids are hydrophobic → ____________________ via stomach churning to get lipid droplets to increase SA for digestive enzymes to get to the lipids

satiety

Lipid Digestion in the Stomach

undigested lipids delay the rate of stomach emptying → high _______ value (feeling full)