Final Exam Flashcards
What are the 4 lipid classes?
- Fatty Acids
- Triacyclglycerols
- Phospholipids
- Cholesterol
Fatty acids have no _____ present, meaning they are fully reduced
oxygens
What are lipids?
Fats, they are a group of organic compounds that are insoluble in water but are soluble in organic solvents
Fatty acids are _______ molecules
amphipathic
What are saturated fatty acids?
Solid hydrocarbon chains with no double bonds or kinks
What are unsaturated fatty acids?
Have one or more double bonds that cause kinks in the acid
There are 2 different kinds of fatty acid nomenclature: ?
- Fatty acid carbon atoms are usually numbered beginning with the carboxyl terminal carbon atom.
Carbon atoms 2 and 3 are also referred to as α and β, respectively. - Fatty acids can also be numbered from the methyl carbon atom, which is called the omega (ω) carbon.
How is the normal nomenclature structured?
E.g. 18:1Δ^9
18 = number of carbons
1 = number of double bonds
9 = double bond location
Fatty acids, a major source of energy, are stored as triacyclglycerols in what kind of tissue?
Adipose
Fatty acids are connected to glycerol by an _____ bond
ester
“Free” fatty acids are highly ____, attaching them to glycerol makes them less so
toxic
What are the 2 sources of triacylglycerol?
- From the diet
- Synthesized in the liver from carbohydrates and proteins if absolutely necessary
____ are the most highly concentrated form of stored biological energy
Triacylglycerol
Triacylglycerol is stored in an _____ form
anhydrous
Triacylglycerol is too _______ to cross biological membranes
hydrophobic
Triacylglycerol is degraded in the small intestine and resynthesized in ?
intestinal cells (enterocytes)
____ break down lipids and usually release a fatty acid
Lipases
Triacylglycerol broken down by lipases and turned into ?
Monoacylglycerol and 2 fatty acids
What is the importance of Chylomicrons?
Fat shuttles, they transport triacylglycerol in the circulation to tissues
Fatty acids are stored as triacyclglycerols in _____ ____ in adipose tissue
lipid droplets
Adipose tissue has a very ___ capacity for triacylglycerol storage
high
In the ____, glycerol from lipolysis in adipose tissue can be used for gluconeogenesis
liver
Fatty Acid Oxidation Occurs in the ?
Mitochondrial Matrix
To be oxidized, fatty acids need to be:
1. ?
2. ?
- Activated (bound to CoA)
- Transported (carnitine shuttle)
What is the rate-limiting step of fatty acid oxidation?
Fatty acid transport into the mitochondria
In an energy surplus the carnitine shuttle is going to have __ activity; but in an energy deficiency the carnitine shuttle is going to have ___ activity
low, high
The ____ step of the carnitine shuttle is regulated, and the enzyme of the step is ?
1st, Carnitine acyltransferase I
What are the 4 basic steps in the β-Oxidation of saturated fatty acids?
- Oxidation
- Hydration
- Oxidation
- Cleavage
What is the 1st step in the β-Oxidation of saturated fatty acids?
Oxidation via Acyl CoA dehydrogenase. Introduces trans double bond (α-β or C2-C3)
What is an Enoyl CoA?
A generic term describing an unsaturated fatty acid bound to CoA
What is the 2nd step in the β-Oxidation of saturated fatty acids?
Hydration via Enoyl CoA hydratase
What is the 3rd step in the β-Oxidation of saturated fatty acids?
Oxidation via Hydroxyacyl CoA dehydrogenase
What is the 4th step in the β-Oxidation of saturated fatty acids?
Thiolysis/cleavage via thiolase. Carbons 1 and 2 of a fatty acid generate each acetyl CoA
In the β-Oxidation of saturated fatty acids, two carbon units are sequentially removed from the ____ end of the fatty acid (carbons bound to CoA)
carboxyl
Fatty acid oxidation continues until ?
the fatty acid is completely oxidized to acetyl CoA
What is the overall NET production of ATP from the oxidation of palmitate (7 cycles)?
106 ATP
What is the importance of Enoyl CoA isomerase?
- Moves double bond from C3-4 to C2-3
- Changes double bond from cis to trans and now becomes an intermediate of the pathway
? is a unique product of the beta oxidation of odd chain fatty acids
Propionyl Co-A
Propionyl Co-A is metabolized by carboxylase to a 4-carbon intermediate that is eventually converted to ?
succinyl Co-A
? are an alternative to glucose as a fuel or energy source
Ketone bodies
Ketone bodies are formed by ketogenesis in the _____ only
liver
Ketone bodies are utilized by extrahepatic tissues (brain) when [?] is low
glucose
Determine which of these ketone bodies are used/not used for fuel:
Acetoacetate: ?
β-hydroxybutyrate: ?
Acetone: ?
Acetoacetate: for fuel
β-hydroxybutyrate: for fuel
Acetone: not for fuel
Ketone body formation occurs in the mitochondria of the ___ where acetyl CoA is produced
liver
Which ketone body does not contribute to acetyl CoA production?
Acetone
Fatty acid biosynthesis occurs in the ____, in the ___ primarily and in adipose
cytosol, liver
Fatty acids are synthesized by a multienzyme complex: ?
Fatty Acid Synthase (FAS)
In fatty acid biosynthesis, the chain length is increased by sequential addition of ___ -carbon units (derived from acetyl CoA)
2
Elongation of fatty acids stops with formation of ______ (C-16)
palmitate
Further elongation/desaturation of fatty acids past palmitate is catalyzed by ?
other enzymes
What is the primary substrate for fatty acid biosynthesis?
Acetyl CoA
_____ is also needed for fatty acid biosynthesis
NADPH
? catalyzes the 1st and rate limiting step of FA biosynthesis
Acetyl CoA Carboxylase
Palmitate is an ____ of acetyl CoA carboxylase, while Citrate is an _____
inhibitor, activator
Glucagon and epinephrine ______ acetyl CoA carboxylase, while insulin ______ it
inactivates, activates
What is the 2nd step in Fatty Acid Biosynthesis?
Loading FAS with substrates. Acetyl-CoA to β-ketoacyl synthase via Acetyl transacylase (AT)
What is the 3rd step in Fatty Acid Biosynthesis?
Formation of acetyl ACP and malonyl ACP charges/primes. Malonyl CoA to Malonyl ACP via Malonyl transacylase (MT)
What is the 4th step in Fatty Acid Biosynthesis?
1st reaction in formation of FA chain, and is a condensation. Activated acetyl and malonyl groups condense forming acetoacetyl ACP. Catalyzed by β-ketoacyl-ACP Synthase
What is the 5th step in Fatty Acid Biosynthesis?
Acetoacetyl-ACP (B-ketobutyryl-ACP) is reduced. Reaction a reduction reaction, and is catalyzed by B-ketoacyl-ACP reductase (KR). Electron donor is NADPH.
What is the 6th step in Fatty Acid Biosynthesis?
Dehydration. Water is removed from C2 and C3 of β-hydroxybutyryl-ACP to introduce a double bond. Product is trans-Δ2-butenoyl-ACP.
What is the 7th step in Fatty Acid Biosynthesis?
Reduction. Double bond of trans-Δ2-butenoyl ACP is reduced to form butyryl-ACP by Enoyl-ACP Reductase. NADPH is the electron donor. One pass through fatty acid synthase is complete.
What is the 8th step in Fatty Acid Biosynthesis?
Translocase. Transfer of butyryl group from ACP to KS. Catalyzed by Acetyl transacylase (AT). The next cycle can then start
What is the 2nd round in Fatty Acid Biosynthesis?
- Malonyl CoA -> Malonyl-ACP is catalyzed by malonyl transacylase (MT)
- Butyryl group is condensed to malonyl ACP
Repeat:
Reduction
Dehydration
Reduction
Translocation
Product = 6 carbon fatty acid
In total, __ cycles of condensation and reduction are required to produce palmitate.
7
What is the overall reaction for the synthesis or palmitate:
__Acetyl CoA + __ATP + __NADPH -> __Palmitate + __CoA + __ADP + __Pi + __NADP+ + __H2O
8, 7, 14, 1, 8, 7, 7, 14, 6
Most fatty acids are ____ than palmitate (18-26C), mono- and ________fatty acids
longer, polyunsaturated
Elongation occurs in _______ ______, and 2 carbons are added at a time from malonyl CoA
endoplasmic reticulum
Humans cannot introduce double bonds past carbon __
9
Desaturation is the introduction of ? and is catalyzed by _______ enzymes
cis double bonds, desaturase
Location of double bond is ____ for each desaturase
specific
Humans lack Δ__ and Δ__ desaturases, and so must obtain _____and _______ through the diet
12, 15, linoleate, α-linolenate
We use linoleate and α-linolenate to make other ?
long polyunsaturated fatty acids
Low energy (↓ AMP): is where AMPK is _____ and AMPK phosphorylates ____ (inactive)
active, ACC
High energy (🠕 ATP): is where is AMPK _____ and ACC is de-phosphorylated (_____)
inactive, active
Acetyl CoA carboxylase activity is ____ by citrate and insulin
increased
Acetyl CoA carboxylase activity is _____ by epinephrine, and glucagon
decreased
Acetyl CoA carboxylase activity is ______ by palmitate?
decreased
Malonyl CoA inhibits ? (carnitine shuttle), and so blocks ?
carnitine acyltransferase I, beta oxidation
Cholesterol is synthesized mainly by the ___, the remainder is from the ____
liver, diet
What are the 2 functions of cholesterol?
- Structural component of membranes
- Precursor of bile salts, steroid hormones, & vitamin D
Where are the 27 carbons in cholesterol from?
Acetyl CoA
Cholesterol is the precursor of 5 steroid hormones: ?
- Cortisol
- Estradiol
- Progesterone
- Testosterone
- Vitamin D
How many reactions are there is the cholesterol biosynthetic pathway?
25
What is the rate limiting step in the cholesterol biosynthetic pathway?
HMG-CoA reductase
Where does the cholesterol biosynthetic pathway occur?
the cytosol
Cholesterol is synthesized in __ stages
4
In cholesterol biosynthesis, there is ___ of NADPH required for these reactions and everything in between and most comes from the ___
LOTS, PPP
What is stage 1 in cholesterol biosynthesis?
Formation of mevalonate. 3 acetyl CoA are used to form it. Here HMG CoA reductase is found, and is the target of statins.
A total of ___ acetyl CoA are used for each molecule of cholesterol formed.
18
Excess cholesterol is converted to bile acids which are stored in _____
gallbladder
What are the 3 fates of cholesterol?
- Hepatocyte plasma membrane
- Bile Acids
- Exported in LDLs
What is an HDL?
High-density lipoprotein. Picks up cholesterol from blood and tissues
What is an LDL?
Low-density lipoprotein. Transport cholesterol from liver to tissues
Regulation of cholesterol synthesis occurs in __ ways:
1. When cholesterol levels in the cell drop, the transcription of the gene for HMG-CoA reductase is ____; transcription slows when cholesterol levels are ___
2. The rate of translation of HMG-CoA reductase mRNA is inhibited by ____ _____
3. The degradation of HMG-CoA reductase enzyme is _____ by elevated levels of ____ cholesterol
3, stimulated, high, mevalonate metabolites, stimulated, cellular
Together the three regulatory processes of cholesterol synthesis can alter the amount of enzyme by over ___-fold!
200
↓ [cholesterol]: leads to __ HMG-CoA reductase, LDL receptor and __ synthesis and __ uptake of cholesterol
🠕, 🠕, 🠕
🠕 [cholesterol]: leads to __ HMG-CoA reductase, LDL receptor, and __ synthesis and __ uptake
↓, ↓, ↓
What is Familial Hypercholesterolemia?
High circulating cholesterol levels, caused by a defective LDL receptor, the cholesterol is not cleared from the blood, causing atherosclerotic plaques
In familial hypercholesterolemia, cholesterol levels get so high they form ?
xanthomas (deposits) in the skin
Cholesterol provides _____ to membranes
fluidity
Fatty acids have 2 fates: 1. and 2.
- Triacylglycerol as metabolic energy
- Phospholipid for membranes
What are the 3 most common phospholipids?
- Phosphatidylcholine
- Phosphatidylethanolamine
- Phosphatidylserine
Triacylglycerol and phospholipids are synthesized from a _____ pathway, what is it called?
common, Kennedy Pathway
? is the starting substrate of TG and PL synthesis
Glycerol 3-phosphate
In the Kennedy pathway, _______ catalyzes the sequential attachment of fatty acids to glycerol backbone (____bond)
acyltransferase, ester
What is the most abundant phospholipid?
Phosphatidylcholine, at 50%
Why is there a second pathway for the synthesis of phosphatidylcholine?
To ensure there is an adequate supply
Where does the methylation pathway of the synthesis of phosphatidylcholine occur?
The liver
What kind of charge do all of the relevant phospholipids have?
positive charge
The synthesis of phosphatidylethanolamine occurs by _________ of phosphatidylserine
decarboxylation
Eicosanoids are derived from ______, which is part of a phospholipid present in a ?
arachidonate, cell membrane
Arachidonate releases by ?
Phospholipase A2
Eicosanoids are termed ?
paracrine hormones
Eicosanoids are not stored and so are ?
rapidly degraded
______ send messages to nearby cells/tissues including the cell in
which it was made
Eicosanoids
The signal for PLA2 activation _____ calcium in the cell; this leads to
______ of PLA2 to the plasma membrane, and phosphorylation of PLA2
which ____ it.
elevates, translocation, activates
Biological actions of eicosanoids are _____ in ____ organs
diverse, various
What are some examples of the biological actions of eicosanoids?
vasodilation, vasoconstriction, platelet aggregation, inhibition of platelet aggregation, contraction of smooth muscle, chemotaxis of leukocytes, release of lysosomal enzymes
What are some of the excess production symptoms of eicosanoids?
pain, inflammation, fever, nausea, vomiting
Where does Aspirin target in the realm of arachidonates?
Prostaglandin synthase
What is the Ubiquitin-proteasome pathway?
For cellular protein turnover. Ubiquitin molecules are linked to a specific lysine. The protein becomes polyubiquitinated, processed into peptides, and the ubiquitin is eventually cleaved and re-utilized
What is proteolysis?
The hydrolytic cleavage if proteins by digestive proteinases; these enzymes are secreted into the stomach and small intestine
Gastric acidic environment _____ proteins
and thus enhances proteolysis
denatures
The K+/H+ Pump in the membrane of specialized
stomach cells pumps ____ into the stomach in
exchange for K+ at the expense of _____ ______;
generates acidic environment and releases ____.
protons, ATP hydrolysis, heat
In some individuals, the K+/H+ pump is overactive, or the esophageal sphincter is weak, which results in
?
gastroesophageal reflux disease (GERD)
What are some medications used to treat GERD?
Antacids, histamine H2 receptor blockers, and proton pump inhibitors
All digestive proteolytic enzymes are secreted from either specialized gastric cells (pepsinogen) or from the
pancreas (others) as ?
inactive zymogens
All zymogens are themselves activated by ?
proteolysis
Why are proteinases are synthesized and stored as
zymogens?
So that they don’t break down proteins in the cells
where they are made/stored and don’t digest themselves prior to secretion
_____ preferentially cleaves peptide bonds between hydrophobic amino acids or aromatic amino acids.
Pepsin
______ cleaves peptide bonds following an Arg or Lys
residue
Trypsin
______ preferentially cleaves peptide bonds after an aromatic amino acid.
Chymotrypsin
______ broader specificity; cuts after amino acids with smaller, hydrophobic side chains such as Gly, Ala,Val
Elastase
What are endopeptidases?
When proteolytic enzymes cleave internal peptide bonds in a substrate
Proteases eventually self-_____
inactivate
The Amino Acids on either side of a peptide bond form a
____ substrate and generally require _____ enzymes
unique, different
Bond between arginine and glycine is cleaved by
_____
trypsin
Bond between tyrosine and serine is cleaved by
________
chymotrypsin
In regards to the specificities of digestive proteolytic enzymes, two groups target either the amino or
carboxy terminal residue of a peptide, these are called _________ or _______ respectively
aminopeptidases, carboxypeptidases
What are the 3 fates of the amino group of amino acids?
Transamination (cytosol)
Oxidative deamination (mitochondria)
Urea Cycle (split between the cytosol and mitochondria)
In the Transamination Reaction, there is a transfer of amino group to an α-ketoglutarate. What are the donors/acceptor?
Donors: L-amino acids
Acceptor: α-ketoglutarate
In the Transamination Reaction, the amino groups get funneled to ?
Glutamate
The Transamination reaction is an obligatory step in the degradation of ?
amino acids (except for Lys and Thr)
True or False: the transamination reaction is reversible?
True, Keq is ~1
What are the enzymes in the transamination reaction?
Enzymes: aminotransferases
Coenzyme: PLP
What are the 2 most important aminotransferases?
Aspartate aminotransferase
Alanine aminotransferase
Where is aspartate aminotransferase found?
In the liver mitochondrion
Where is alanine aminotransferase found?
Muscle cytosol
_____ phosphate (an aldehyde) is an a-amino group acceptor; _______ phosphate is an a-keto (ketone) group acceptor
Pyridoxal, pyridoxamine
In ______ phosphate, the amino group of incoming α-amino acid forms covalent linkage with aldehyde group, and the α-keto acid leaves
pyridoxal
In _______ phosphate, the ketone group of incoming α-keto acid (typically α-ketoglutarate) forms covalent linkage with amino group. Amino group then
displaced again by active site lysine amino group. Glutamate leaves.
pyridoxamine
The incoming amino acid amino group displaces the
lysine amino group, in a fully _____ reaction, and
forms an identical _____ of PLP
reversible, aldimine
What is aldimine?
A chemical term that defines an imine (C=N group) derived from an aldehyde
An aldimine is also called a ?
Schiff base
What is the ping-pong nature of the aminotransferase reaction?
In which when the first substrate (amino acid) is bound to the enzyme (via PLP) and reacts (pyridoxamine phosphate), the second substrate (α-ketoglutarate) cannot bind to form second product (L-glutamate) till the first product (α-keto acid) leaves
What is the α-keto acid pair to alanine?
pyruvate
What is the α-keto acid pair to aspartate?
Oxaloacetate
What is the α-keto acid pair to glutamate?
α-ketoglutarate
What is an α-keto acid?
Means there is a ketone group adjacent to a carboxylate group
Aminotransferases are important markers for ?
liver or heart damage
High serum levels of _____ aminotransferase (also called Glutamate Pyruvate Transaminase or GPT) indicative of damage. Same goes for _____ aminotransferase (also called Glutamate Oxaloacetate Transaminase or GOT).
alanine, aspartate
Fate of Glutamate in Liver is to be transported to the mitochondria and undergoes oxidative deamination to release ?
ammonia
Oxidative deamination of glutamate is done via which enzyme?
Glutamate dehydrogenase
Oxidative deamination removes the amino group from glu as ? and is a reversible reaction
NH4
What is the coenzyme in oxidative deanimation?
NAD+ or NADP+
High concentrations of NH4+ are ?
toxic
NH4+ is converted to urea in the ?
liver mitochondria
Excess ammonia in non-liver tissues is transported as _____ to the liver
glutamine
What is the nontoxic transport form of NH4+?
Glutamine
In the liver, NH4+ is released from glutamine by cleavage by which enzyme?
Mitochondrial glutaminase
Alanine transports excess ammonia from muscle tissue to ?
liver
In muscle, glutamate is formed from ?.
transaminations
The glutamate amino group is ultimately transaminated to pyruvate, forming _____. Once in liver, alanine is transaminated to form ______.
alanine, glutamate
Alanine carries ______ from muscle to liver
Nitrogen
NH4+ is converted to urea in the ?
liver
Where does the urea cycle occur?
The liver
What are the 3 precursors of urea?
NH4+, CO2, and Aspartate
Historically, urine was a valuable diagnostic tool for defects in ?
nitrogen metabolism
In the urea cycle, there are __ cytosolic enzymes that exist as a multiprotein complex
3
______ and _____ must be transported in and out of the mitochondria respectively during the cycle
Ornithine, citrulline
