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
? is a major regulation point but is actually not part of the urea cycle
Carbamoyl Phosphate Synthetase I (CPS I)
The formation of carbamoyl phosphate occurs in the ?
mitochondrial matrix
What is the enzyme used in the formation of carbamoyl phosphate?
CPS I
How is CPS I regulated?
allosterically
What is the first key regulatory step in urea cycle?
The formation of carbamoyl phosphate
How many ATP molecules are consumed in the formation of carbamoyl phosphate?
2
The formation of N-acetylglutamate is done via which enzyme?
N-acetylglutamate synthase
What is happening during the formation of N-acetylglutamate?
Amide bond formation between α-amino group of glutamate and activate carbonyl carbon of acetate
The formation of N-acetylglutamate is _______ regulated and only occurs in the presence of _____ amino acids in the liver
allosterically, excess
The product N-Acetylglutamate is a required allosteric activator of ?
CPS I
Citrullene is formed in the ?
Mitochondrion
Ornithine is the first cousin of ____, as it has one ____ CH2 group
lysine, fewer
What is going on in the formation of citrulline?
An amide bond is formed between ornithine and carbamoyl phosphate
What is the important aspect of citrulline?
It can be transported to the cytosol
Citrulline is formed via which enzyme?
Ornithine transcarbamoylase
Argininosuccinate is formed from citrulline and aspartate via which enzyme?
Argininosuccinate synthetase
Argininosuccinate formation occurs in the ?
cytosol
In the formation of argininosuccinate, what intermediate is formed?
L-citrulline adenylate
The role of aspartate in the formation of argininosuccinate is to ?
ultimately donate the 2nd NH3 group to urea
the formation of arginine and fumarate by argininosuccinate is done via which enzyme?
Cytosolic argininosuccinase or argininosuccinate lyase
In the formation of arginine, the other product fumarate can be converted to ?
malate
The malate formed by the fumarate (made via the formation of arginine) then goes back to the mitochondrion to feed into which cycle?
TCA
The malate formed by the fumarate (made via the formation of arginine) can also be converted to ______ and/or ______
oxaloacetate, aspartate
Which cycle supplies most of the arginine requirements for adults?
Urea
The hydrolysis of arginine is via which enzyme?
Cytosolic arginase
In the hydrolysis of arginine, ____ is finally formed and ____ is regenerated
urea, ornithine
What is the overall stoichiometry of the urea cycle:
__CO2 + __NH4+ + __ATP + __Aspartate + __H2O -> __Urea + __ADP + __Pi + __AMP + __PPi + __Fumarate
1, 1, 3, 1, 2, 1, 2, 2, 1, 1, 1
A single urea cycle enzyme deficiency will result in _______, or elevated NH4+ in the blood, and is incredibly toxic to the ____ system
hyperammonemia, nervous
Citrullinema is a result of what deficiency?
Argininosuccinate lyase deficiency
Patients with liver cirrhosis cannot process ?
ammonia to urea
Urea cycle requires an ____ of amino acids in the liver, is typically very active in ___ protein diets, very active during _____, and the leftover carbon skeletons are shunted to the ? or to ?
excess, high, starvation, TCA cycle, gluconeogenesis
Why is the urea cycle active during starvation?
The human body can’t utilize carbohydrates as an energy source, so proteins present in the muscles are broken down and hence use amino acids as energy sources. Since there is an enhancement in the amino acid degradation, more urea is produced
What is argininemia?
Defective arginase in urea synthesis, and causes mental retardation
What is argininosuccinicacidemia?
Defective argininosuccinase in urea synthesis, and causes vomiting and convulsions
What is carbamoyl phosphate synthetase 1 deficiency?
Defective carbamoyl phosphate synthetase 1 in urea synthesis, and causes lethargy, convulsions, and early death
What is maple syrup urine disease (branched chain ketoaciduria)?
Defective branched-chain α-keto acid dehydrogenase complex in isoleucine, leucine, and valine degradation, and it causes vomiting, convulsions, mental retardation, and early death
What is phenylketonuria?
Defective phenylalanine hydroxylase in the conversion of phenylalanine to tyrosine, leads to a phelylalanine buildup in the blood, and causes neonatal vomiting and mental retardation
What are the 2 main treatment options for deficiencies in urea cycle enzymes?
Supplemented diet with benzoate and phenylbutyrate
How do treatments like benzoate and phenylbutyrate work?
Form enzyme-catalyzed amide linkages with glycine or glutamine α-amino groups. The resultant products, benzoylglycine and phenylacetylglutamine are then excreted in urine. This can help deplete the liver nitrogen pool, eventually lowering the ammonia levels in blood
In the liver, free ammonium is produced from
breakdown of Serine and Threonine by ? and ?
serine dehydratase, threonine dehydratase
In the liver, the breakdown of Serine gives ____ and ___ and Threonine gives ______ and ____
pyruvate, NH4+, α-ketobutyrate, NH4+
In the kidney, ammonia is generated by the metabolism of glutamine by enzymes ? and ?, and is secreted in urine as ?
glutamate dehydrogenase, glutaminase, free ammonium
Other sources of ammonia includes amines from the ___, monoamines that serve as ______/__________, and from the catabolism of _____ and _______
diet, hormones, neurotransmitters, purines, pyrimidines
The carbon skeletons of all 20 amino acids are broken
down and fed into only seven central metabolites: ?
Pyruvate, oxaloacetate, α-ketoglutarate, succinyl CoA, fumarate, acetyl CoA, acetoacetyl CoA
Which of the seven central metabolites are glucogenic, which are ketogenic?
Glucogenic: pyruvate, oxaloacetate, α-ketoglutarate, succinyl CoA, fumarate
Ketogenic: acetyl CoA, acetoacetyl CoA
There are only two amino acids that are purely ketogenic: ?
Leucine and lysine
What is the difference between glucogenic and ketogenic?
Glucogenic amino acids can be converted into glucose, which can then be used to produce energy. Ketogenic amino acids can be converted into ketone bodies.
______ breakdown generates products that are ketogenic and glucogenic: ______ is ketogenic, _____ is glucogenic via gluconeogenesis.
Phenylalanine, acetoacetate, fumarate
The liver lacks the branched chain _______, so breakdown occurs in _____, ____, and _____ tissue.
aminotransferase, kidney, brain, adipose
_______, ______, ______, and _____ are all converted to glutamate, and then broken down to α-ketoglutarate
Glutamine, proline, arginine, histidine
α-ketoglutarate and pyruvate are the most common ways of breaking down your ?
carbon skeletons
It is estimated that about __% or 10^11 (100 Billion) kg comes from ?
60, nitrogen-fixing microorganisms
Nitrogenase itself is very sensitive to inactivation by ?
O2
Both the reductase and nitrogenase are ? proteins
iron-sulfur cluster (Fe-S)
The ____ Cofactor is only found in nitrogenase
MoFe
Humans have __ Mo-requiring enzymes and all require the pterin Mo Cofactor
4
? is a primary control point of nitrogen metabolism
Glutamine synthetase
Glutamine Synthetase is present in ____ organisms.
all
Glutamine is _____ source of amino groups in many Biosynthetic Reactions
primary
Glutamine synthetase is an allosteric _____ (12 identical subunits)
dodecamer
Glutamine Synthetase activity is controlled by 8 _____ regulators
allosteric
Combined effect of allosteric effectors in glutamine synthetase is more than ____.
additive
Covalent modification of Glutamine synthetase by _____ makes the enzyme more responsive to allosteric inhibitors.
adenylation
Adenylylation of Glutamine Synthetase occurs on a ____ residue
tyrosine
Adenylation of Glutamine Synthetase leads to its _____, and is the ?.
inactivation, regulatory step
Glutamine is the major source of the donor amino group in the formation of ?
amides
All amino acids are built from intermediates of which 3 pathways?
Glycolysis, TCA cycle, PPP
What are the nonessential amino acids for humans?
Alanine, asparagine, aspartate, glutamate, serine
What are the two conditionally essential amino acids for humans?
Arginine, glutamine, and tyrosine
Why are arginine, glutamine, and tyrosine considered conditionally essential amino acids?
Specific populations who do not synthesize it in adequate amounts, such as new born infants and people with diseased livers who are unable to synthesize cysteine, must obtain one or more of these from their diet
In tetrahydrofolate, the two ____ atoms are the sites where the 1 carbon units get attached
nitrogen
Can we synthesize tetrahydrofolate?
No
What are the terms synonymous with the 1-C unit “methyl”?
N^5, or -CH3
What are the terms synonymous with the 1-C unit “methylene”?
N^5N^10, or -CH2-
What are the terms synonymous with the 1-C unit “formyl”?
N^10, or -CHO
What are the terms synonymous with the 1-C unit “methenyl”?
N^5N^10, or -CH=
N^5-formimino-tetrahydrofolate is involved in ______ metabolism
histidine
The conversion of tetrahydrofolate to N^5,N^10-methylene-tetrahydrofolate requires the conversion of serine to ?
glycine
Methionine synthesis entails the conversion of homocysteine to methionine via what enzyme?
methionine synthase
Methionine synthesis also involves the conversion of N^5 methyltetrahydrofolate to ?
Tetrahydrofolate coenzyme B12
When you convert serine to glycine, you liberate a group that ends up on ?
tetrahydrofolate
S-Adenosylmethionine (SAM) is a ____ donor in many biosynthetic reactions
methyl
When S-Adenosylmethionine is used as a methyl donor, the product is ?
S-Adenosylhomocysteine
Hydrolysis of S-Adenoyslhomocysteine yields ______ and ______. Homocysteine has __ more CH2 group than cysteine
adenosine, homocysteine, 1
? supplies the CH3- group for methionine biosynthesis
N^5-methyltetrahydrofolate
Where the adenosine is linked to methionine?
The sulfur atom
Methyl group usually transfers to a _____ or
_____ atom
nitrogen, oxygen
Valine ____ threonine deaminase, while isoleucine ____ threonine deaminase.
activates, deactivates
What is the amino acid precursor of sphingosine?
Serine
What is the amino acid precursor of histamine?
histidine
What is the amino acid precursor of thyroxine?
Tyrosine
What is the amino acid precursor of epinephrine?
Tyrosine
What is the amino acid precursor of serotonin?
Tryptophan
What is the amino acid precursor of nicotinamide unit of NAD+?
Tryptophan
What is the amino acid precursor of 5,6-Dihydroxyindole?
Tryptophan
What is the amino acid precursor of L-Dopamine?
Tyrosine
What is the amino acid precursor of Gamma-aminobutyric acid (GABA)?
Glutamate
What is the amino acid precursor of heme?
Glycine
While only 5% of nucleosides absorbed are reutilized for nucleic acid synthesis, 25% of these are used by the rapidly regenerating _____ (specialized intestinal cells).
enterocytes
In the intestinal lumen, the conversion of nucleic acids to nucleotides uses which enzyme?
Nuclease enzymes, phosphodiesterases
In the intestinal lumen, the conversion of nucleotides to nucleosides uses which enzyme?
Alkaline phosphatase enzymes
In the intestinal lumen, the conversion of nucleosides to purines and pyrimidines uses which enzyme?
Nucleosidase enzymes
For the base Adenine, what is the corresponding:
1. Ribonucleoside
2. Ribonucleotide
3. Deoxyribonucleoside
4. Deoxyribonucleotide
- Adenosine
- Adenylate (AMP)
- Deoxyadenosine
- Deoxyadenylate (dAMP)
For the base Guanine, what is the corresponding:
1. Ribonucleoside
2. Ribonucleotide
3. Deoxyribonucleoside
4. Deoxyribonucleotide
- Guanosine
- Guanylate (GMP)
- Deoxyguanosine
- Deoxyguanylate
For the base Uracil/Thymine, what is the corresponding:
1. Ribonucleoside
2. Ribonucleotide
3. Deoxyribonucleoside
4. Deoxyribonucleotide
- Uridine
- Uridylate (UMP)
- Thymidine
- Thymidylate (TMP)
For the base Cytosine, what is the corresponding:
1. Ribonucleoside
2. Ribonucleotide
3. Deoxyribonucleoside
4. Deoxyribonucleotide
- Cytidine
- Cytidylate (CMP)
- Deoxycytidine
- Deoxycytidylate (dCMP)
What are the 7 uses of nucleotides?
- Precursors of DNA and RNA
- ATP
- Adenine nucleotides are the components of 3 major coenzymes (NAD, FAD, Coenzyme A)
- Activated intermediates
- Metabolic and physiologic regulators
- GTP is used in signal transduction pathways
- CTP is used in the biosynthesis of glycerophospholipids
What is the De Novo pathway?
Activated ribose (PRPP) + amino acids + ATP + CO2 -> Nucleotide
What is the Salvage pathway?
Activated ribose (PRPP) + base -> Nucleotide
In the De Novo pyrimidine biosynthesis (UTP, CTP), pyrimidines are built from ?
Carbamoyl phosphate, aspartate, and PRPP
In the De Novo pathway of pyrimidine nucleotide (UMP and CMP) biosynthesis, what are the precursors?
Ribose-5-phosphate, CO2, Gln, Asp
What are the steps in the De Novo pathway of pyrimidine nucleotide (UMP and CMP) biosynthesis?
- Synthesize carbamoyl phosphate
- Build the pyrimidine ring (orotate) from aspartate
- Link orotate to ribose-5-phosphate
What is the rate limiting step in pyrimidine synthesis and its corresponding enzyme?
Synthesis of carbamoyl phosphate, the enzyme is Carbamoyl Phosphate Synthetase II (CPS II)
Compare the metabolic process of CPS I to CPS II?
CPS I: urea synthesis
CPS II: pyrimidine synthesis
Compare the location of CPS I to CPS II?
CPS I: mitochondrial matrix
CPS II: cytosol
Compare the N donor of CPS I to CPS II?
CPS I: NH4+
CPS II: glutamine
Compare the regulator effectors of CPS I to CPS II?
CPS I: + = N-acetylGlu, arginine
CPS II: - = CTP, + = ATP, PRPP
Aspartate transcarbamoylase (ATCase) is an _______ regulated control point
allosterically
What is an inhibitor of ATCase? What is an activator of ATCase?
CTP, ATP
What yields orotate?
Ring closure and oxidation
The formation of PRPP from Ribose 5-phosphate uses what enzyme? This enzyme is highly regulated, but by ____ end products (not ______).
PRPP synthetase, purine, pyrimidines
Orotidylate decarboxylase catalyses formation of ? from orotidylate
uridylate
Both Orotate phosphoribosyl transferase and Orotidylate decarboxylase activities are found on a _____ polypeptide chain. The bifunctional enzyme is called ?
single, uridine monophosphate synthetase
Formation of CTP from UTP requires ______, ___ and the enzyme ?
glutamine, ATP, cytidylate synthetase
Pyrimidine Nucleotide Biosynthesis:
The pyrimidine ring is first synthesized to form ______. Then N1 of Orotate is covalently linked to C1 of the _____ using PRPP as the _____. ________ is the leaving group. Orotidylate is then enzymatically decarboxylated to form ____. ___ is then formed from UMP (__ ATP molecules are used up). Then ___ is formed by the addition of NH3 to UTP (from Glutamine).
orotidylate, ribose, precursor, pyrophosphate, UMP, UTP, 2, CTP
Ribonucleotide Reductase (RNR) makes deoxy NDP’s from ____
NDP’s
Note that dUDP and dUTP are dephosphorylated to ____, then converted to ___
dUMP, dTMP
Order these statements for the conversion of dUMP to dTMP:
1. N5,N10 methylene THF is then regenerated by the action of serine hydroxymethyl transferase.
2. THF is regenerated by reduction of dihydrofolate by dihydrofolate reductase using NADPH
3. Methylation of dUMP by 1-C (CH2) transfer (N5,N10 methylene THF)
3, 2, 1
How do chemotherapeutic agents work?
Inhibition of biosynthesis of DNA is the basis for some chemotherapies
Where is the impact caused by fluorouracil in THF synthesis?
Thymidylate synthase, in the conversion of dUMP to TMP
Where is the impact caused by trimethoprim in THF synthesis?
Dihydrofolate reductase, in the conversion of dihydrofolate to tetrahydrofolate
Fluorouracil is what kind of inhibitor?
Suicide
Methotrexate and Aminopterin are effective competitive inhibitors of _______
DHFR - dihydrofolate reductase
_______ has a 1000x fold greater affinity for DHFR than does dihydrofolate and is a competitive inhibitor
methotrexate
Methotrexate, aminopterin, and trimethoprim are also used to treat some _____ disorders such as rheumatoid arthritis and eczema
autoimmune
________ binds and inhibits both bacterial and protozoan DHFR enzymes very effectively (10^5 more so than Human DHFR).
Trimethoprim
_______ is often used in combination with other drugs to combat bacterial or protozoan infections.
Trimethoprim
______ is used to treat herpes simplex infections (various herpes viruses), and herpes zoster infections (chicken pox, shingles).
Acyclovir
Acyclovir is considered what kind of medication?
Antiviral
The following paragraph describes the Mechanism of action of what kind of medication?
Herpes viruses have a thymidine kinase which has a broad substrate specificity. Herpes TK, but not the human enzyme, will phosphorylate acyclovir. Acyclovir phosphate is a dGTP analog for the viral DNA polymerase. No 3’-OH group, hence after incorporation, termination of viral DNA synthesis.
Antiviral acyclovir
? : is a reverse transcriptase inhibitor which is a nucleoside analog. One component of an HIV cocktail.
Zidovudine and/or Azidothymidine
Zidovudine and/or Azidothymidine is considered what kind of medication?
Antiviral
The following paragraph describes the Mechanism of action of what kind of medication?
Cellular enzymes first convert azidothymidine to the 5’ triphosphate. Acts as a thymidine analog; gets incorporated into the DNA. Links to normal nucleotide 3-OH via its 5’ triphophate. The azido group on C3 the prevents further phosphodiester bond formation and DNA elongation.
Zidovudine and/or Azidothymidine
In the interconversion of nucleoside monophosphate kinase, its always the _______ that gets phosphorylated to the diphosphate, and its specific for the _____ not the sugar
monophosphate, base
What are the Three types of pathways in the Biosynthesis of Purine Nucleotides?
(1) De novo pathway (starting from the beginning)
(2) Salvage pathway (recycling bases)
(3) Very little is used from dietary sources
What are the 6 precursors for the de novo pathway is the Biosynthesis of Purine Nucleotides?
- Ribose-5-P
- Aspartate
- CO2
- Glycine
- Glutamine
- Formate
What is the main strategy in the biosynthesis of purine nucleotides?
Build the purine ring onto the ribose-5-P one atom or few atoms at a time
Formation of Inosinate then leads to formation of
______ and ______.
Adenylate, Guanylate
The first step in Purine Synthesis adds ______ to ? It is also highly _____
ammonia, C1 of ribose-5-P, regulated
What is the reaction of the first step in purine synthesis?
5-phosphoribosyl-1-pyrophosphate (PRPP) is converted to 5-phospho-β-D-ribosylamine, via glutamine-PRPP amidotransferase and the conversion of glutamine to glutamate and PPi
The product of the first step in purine synthesis is _____ and soon decomposes, so it has to be quickly utilized in the next step of the pathway. This reaction is regulated by ______ ______. Note, ______ is the origin of the amino group.
unstable, feedback inhibition, glutamine
There is ______ regulation of GMP and AMP synthesis: GTP is required for IMP → AMP, and ATP is required for IMP → GMP
Reciprocal,
Purine degradation results in ?
Uric Acid (Urate)
What is the purine degradation reaction resulting in uric acid?
Xanthine is converted to uric acid, and then urate via the enzyme xanthine oxidase
_____ is only moderately soluble, tends to crystallize if in excess, but it is a very good antioxidant.
Urate
_____ is characterized by high blood levels of uric acid or urate due to overproduction or underexcretion of uric acid
Gout
Uric acid crystals deposit in joints causes ?
pain and inflammation, essentially arthritis
What is the treatment for gout?
Drugs. e.g. allopurinol
Allopurinol reacts with xanthine oxidase to produce ______, which is an inhibitor of xanthine oxidase
Oxypurinol
Most purines from diet are converted to ? which is (hopefully) excreted
uric acid
What are the two main enzymes used in the salvage pathways for purine nucleotide biosynthesis?
Adenine phosphoribosyltransferase (APRT), this is the minor enzyme of the two
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
What is Lesch Nyhan Syndrome?
Deficiency in HGPRT activity due to mutations in the gene
Lesch Nyhan Syndrome is an X-linked disease, thus primarily affects ____
males
? comes with severe intellectual deficits, motor dysfunction, self-mutilation, and very aggressive behavior. The combination of increased synthesis and decreased utilization of purines leads to high levels of uric acid production
Lesch Nyhan Syndrome
What is the most dangerous aspect of Lesch Nyhan Syndrome?
It does not respond to allopurinol treatment
What is a major aspect of the intricate regulation and integration of metabolic pathway?
Allows metabolic pathways to respond rapidly to the needs of the cell/organism
What are the 5 most common mechanisms of regulation in metabolic pathways?
- Allosteric modulators
- Covalent modification
- Proteolysis
- Induction or repression of enzyme synthesis
- Compartmentalization
Hormones are signals from outside the cell that allow communication between ____ and ____ as well as integrate and coordinate the metabolic activities of ______ _____
cells, tissues, different tissues
The human body uses and regenerates approximately its own body weight in ATP per day, which corresponds to about __-__kg of ATP/day
50-75
What are the 3 sources of carbohydrates, fat, and proteins?
- Diet
- Circulating Fluid (blood)
- Stored fuel
There are 6 sources of carbohydrates, fat, and proteins from circulating fluid (blood):
1. Glucose from diet and ______
2. Lactate from _____ metabolism
3. Glycerol and fatty acids from ? in adipose tissue
4. Ketone bodies synthesized in the ____
5. Triacylglycerol transported as ?
- ____ contains triacylglycerol from dietary fatty acids
- ____ contains triacylglycerol produced in the liver
6. Amino Acids from ___ or ______ of body proteins
- gluconeogenesis
- anaerobic
- lipolysis of triacylglycerol
- liver
- plasma lipoprotein, chylomicron, VLDL
- diet, proteolysis
Stored fuel comes in 3 different forms: ?
- Glycogen
- Triacylglycerol
- Proteins
How much liver glycogen in grams compared to muscle glycogen?
Liver: ~100g
Muscle: ~500g
How much triacylglycerol in the body in grams?
~15000
Triacylglycerol is the ____ of stored energy in the body, and can be stored in virtually ______ amounts
bulk, unlimited
How much protein in the body in grams?
~6000
Stored fuel in protein form has no storage form independent of ______
function
_________ are the most highly concentrated form of stored biological energy
Triacyclglycerols
Tissues and organs have specialized functions and, therefore, they have different ____ _______ and ?
fuel requirements, patterns of metabolism
Type of fuel utilized by these tissues vary with the ______ and _______ states of the individual, and level of _____
nutritional, hormonal, activity
Brain and RBC only use ____ as energy source
glucose
The brain, given its small size, utilizes a big proportion and overconsumption of _____
glucose
Some organs function as substrate/energy providers: such as the ___ and ? ensure that consumer organs, especially _____, ____, and ? are always supplied with fuel.
liver, white adipose tissue, brain, muscle, red blood cells
The _____ ____ absorbs nutrients from the diet; moves them into blood or lymphatic system
small intestine
The _____ ___ carries nutrients from intestine to liver
portal vein
The _____ processes fats, carbohydrates, proteins from diet; synthesizes and distributes lipids, ketone bodies, and glucose for other tissues; converts excess nitrogen to urea
liver
The ______ secretes insulin and glucagon in response to changes in blood glucose concentration
pancreas
The _____ transports ions to maintain membrane potential; integrates inputs from body and surroundings; sends signals to other organs
brain
The _____ _____ uses ATP generated aerobically to pump blood
cardiac muscle
The _____ _____ carries lipids from intestine to liver
lymphatic system
The _____ ____ synthesizes, stores, and mobilizes triacylglycerols.
adipose tissue
The ____ _____ uses ATP generated aerobically or anaerobically to do mechanical work
skeletal muscle
Glucokinase in liver is not inhibited by ?
G6P (glucose-6-phosphate)
_____ has high capacity for glucose uptake
Liver
? is at the crossroads of carbohydrate metabolism in the liver
Glucose 6-phosphate
Glucose export is used to maintain blood [glucose] for use by ____
brain
In liver, during the ___ state, glucose is used for conversion to ATP, glycogen, fatty acids, cholesterol, NADPPH, and nucleotides; but in the ____ state, glycogen and gluconeogenesis is used to generate glucose
fed, fasting
Liver acts as a glucose _____
sensor
Liver acts as a glucose sensor and there are three features contribute to this:
1. Liver has a specific glucose transporter, ____, which has a high ___ for glucose which means it can respond to increasing glucose concentrations
2. Liver also has a specific hexokinase called ______; it too has a high Km for glucose and is not inhibited by _______
3. Liver glycogen phosphorylase a is inhibited by ______
GLUT2, Km, glucokinase, glucose-6-P, glucose
In liver, during the ___ state, amino acids are converted to proteins, nucleotides, or are exported; but in the ____ state, amino acids are used to make glucose and ATP
fed, fasting
In liver, during the ___ state, fatty acids are converted to triacylglycerol and phospholipids; but in the ____ state, fatty acids are converted to ATP and ketone body production
fed, fasting
A major role of the liver is to produce fuel from nutrients taken up from blood to be used by ?
other organs
The liver takes up _____ and _____ released from muscle and glycerol released from adipose to synthesize glucose via gluconeogenesis
alanine, lactate
There is no significant ____ in the brain
glycogen
In brain, during the ___ state, glucose is converted to ATP; but in the ____ state, glucose and ketone bodies are used for ATP
fed, fasting
During prolonged fasting, ketone bodies can provide as much as ___% of the energy in the brain
70
In fat cells, during the ___ state, glucose is converted to ATP, NADPH, as well as Acetyl CoA and DHAP, which are converted to Fatty acyl CoA and glycerol 3P, fatty acids are converted to triacylglycerol; but in the ____ state, lipolysis occurs
fed, fasting
In fat cells, most ATP needs are met through ?
β-oxidation
What are myocytes?
Skeletal muscle cells
Since muscle lacks glucose-6-phosphatase, the glucose released from glycogen is metabolized
through ____
glycolysis
Some lactate in blood is used by heart and oxidized to CO2; has specific isozyme of LDH which favors conversion to _____
pyruvate
At _____ activity in skeletal muscle cells, glucose is converted to ATP and lactate, glycogen to glucose, and fatty acids to ATP
maximum
In skeletal muscle cells during the _______ state, fatty acids are converted to ATP
resting
The heart obtains most of its ATP through ______ ______ using fatty acids
oxidative phosphorylation
Insulin, glucagon and epinephrine are the major metabolic hormones: ______ and _____ are synthesized and stored in the pancreas while _____ is synthesized in the adrenal gland
insulin, glucagon, epinephrine
Insulin, glucagon, and epinephrine are termed _____ hormones which means they are secreted into the blood to act on other tissues including the major metabolic organs discussed already
endocrine
Its important to note that insulin, glucagon, and epinephrine do not necessarily have effects on all tissues, only those that have ?
receptors on their cell surface
Insulin, glucagon, and epinephrine ensure that adequate fuels are available for the different
tissues in the body or that dietary nutrients are properly stored and metabolized → ?
maintain metabolic homeostasis
Because insulin, glucagon, and epinephrine can simultaneously act on different tissues, they can
coordinate metabolic processes to more effectively achieve the ?
desire effect
The primary signal for insulin secretion is ____; fatty acids and some specific amino acids can augment this , so insulin levels rise shortly after eating and signal the fed state
glucose,
Since sustained high levels of glucose in blood is damaging to cells, the metabolic effects of insulin are related to _____ blood glucose and to properly manage, store, metabolize this nutrient
lowering
One of the primary, initial effects of insulin is to stimulate glucose ___ into cells
uptake
Insulin: __ glucose uptake, __ glycolysis, __ acetyl-CoA production, __ glycogen synthesis, __ triacylglycerol synthesis, __ gluconeogenesis, __ lipolysis
Signals fed state: __ blood glucose level, __ fuel storage, __ cell growth and differentiation
↑, ↑, ↑, ↑, ↑, ↓, ↓, ↓, ↑, ↑
The primary signal for glucagon release from the pancreas is a ____ in blood glucose levels
drop
A major action of glucagon is to stimulate _____ of glucose from liver by activating glycogenolysis and gluconeogenesis
release
Glucagon also stimulates _____ which provides an additional brain fuel to take some pressure of glucose usage
ketogenesis
Glucagon also stimulates ? in adipose, which release fatty acids which can be used as an alternative fuel by many tissues, again taking the pressure off of glucose usage
TAG breakdown
Glucagon: __ cAMP level, __ glycogenolysis, __ glycogen synthesis, __ triacylglycerol hydrolysis and mobilization, __ gluconeogenesis, __ glycolysis, __ ketogenesis
Signals fasting state: __ blood glucose level, __ glucose release from liver, __ ketone bodies as an alternative fuel for brain
↑, ↑, ↓, ↑, ↑, ↑, ↓, ↑, ↑, ↑, ↑
_______ is released from adrenal glad under stressful situations that require energy
Epinephrine
The main target organs of ______ are liver, muscle and adipose, which provide fuel for the muscle to produce ATP
epinephrine
In ______, epinephrine stimulates glycogen breakdown and glucose release; in ____, epinephrine stimulates TAG breakdown and fatty acid release; in ______, epinephrine stimulates glycogen breakdown and glycolysis
liver, adipose, muscle
Epinephrine: __ cAMP level, __ glycogenolysis, __ glycogen synthesis, __ triacylglycerol mobilization, __ glycolysis
Signals stress: __ blood glucose level, __ glucose release from liver
↑, ↑, ↓, ↑, ↑, ↑, ↑
The normal blood glucose (mg/100mL)
60-90, or ~3mM to ~5mM
What is “hypoglycemic”?
Anything less than 40mg/100mL, causes lethargy, convulsions, and coma
What happens if your blood glucose goes below 10mg/mL or ~0.5mM?
If prolonged, permanent brain damage, and death
What is “hyperglycemic”?
Anything above 140mg/100mL, causes cataract, convulsion, coma, death
What is the “Early Phase” in the 3 phases of starvation?
1 day
In the ____ phase: glucagon levels rise in response to dropping glucose, insulin goes down; glucose uptake decreases to preserve for brain; gluconeogenesis and glycogenolysis in liver stimulated; no problem maintaining blood glucose; TAG hydrolysis in adipose is mildly stimulated, glycerol released is substrate for gluconeogenesis while fatty acids energy source for many tissues; metabolically this is an easy challenge to handle
early
What is the “Mid Phase” in the 3 phases of starvation?
2-3 weeks
In the ____ phase: liver glycogen now completely depleted; body tries to lower its utilization of glucose; TAG hydrolysis in adipose is further elevated; but amount of glycerol released is inadequate to provide sufficient substrate for gluconeogenesis; as a result, muscle degradation begins which releases amino acids; glucagon stimulates ketone body production; excessive fatty acid oxidation in liver provides lots of acetyl CoA substrate; brain derives about a third of its energy from ketone bodies
Mid
Muscle wasting actually begins about Day __ of starvation
3
What is the “Late Phase” in the 3 phases of starvation?
> 3 weeks
In the ____ phase: TAG hydrolysis in adipose continues to provide most of the body’s energy needs; muscle degradation slows dramatically in attempts to spare whatever muscle remains; this reduces glucose production; ketone body production increases even further; brain derives about two-third of its energy from ketone bodies; this phase lasts depends on the size of the fat depot
Late
The degradation of non-muscle cellular protein produces many symptoms, people often die from an _____ _____ rather than directly from ______ although reduction in heart function does occur
infectious disease, starvation
_______ _____ is the collective name for a group of disorders characterized by persistent hyperglycemia
Diabetes Mellitus
_____ _____ is the leading cause of adult blindness, amputation, renal failure, heart attack and stroke
Diabetes Mellitus
What is the fasting glucose blood level in Diabetes Mellitus?
> 7mM
The major effects of ______ include: urinary loss of H2O, glucose, electrolytes, dehydration of cells, cellular malfunction and can cause coma, glycation of plasma proteins (HbA1c), cataracts
hyperglycemia
What are the 2 tests that can help diagnose Diabetes?
- Glucose tolerance test
- Blood HbA1C test
What is the Glucose tolerance test?
Drink glucose solution, measure blood [glucose] over a period of several hours
What is the Blood HbA1C test?
HbA1C test result reflects your average blood sugar level for the past two to three months, and measures the amount of blood sugar attached to your hemoglobin proteins (glycated)
The ____ your A1C level is, the poorer your blood sugar control and the higher your risk of diabetes
higher
What are the 2 main aspects of Type 1 Diabetes Mellitus?
- Insulin-Dependent Diabetes Mellitus (IDDM)
- Juvenile onset
What are the 2 main aspects of Type 2 Diabetes Mellitus?
- Non-insulin-Dependent Diabetes Mellitus (NIDDM)
- Maturity onset
Type __ Diabetes Mellitus accounts for ~10% of diabetics and is characterized by deficiency of insulin
1
Type __ Diabetes Mellitus is caused by an autoimmune attack of the β-cells of pancreas due to: environmental factors or genetic determinants that allow cells to be recognized as “non-self” by the immune system
1
Clinical characteristics of Type __ Diabetes Mellitus:
o frequent urination (polyuria)
o excessive thirst (polydipsia)
o excessive hunger (polyphagia)
* usually accompanied by fatigue and weight loss
1
What is the treatment for type 1 Diabetes Mellitus?
Insulin therapy to regulate blood glucose
In diabetes, there is hyperglycemia due to:
__ glucose uptake, __ glycogen breakdown, __ gluconeogenesis. There is also a __ ketone bodies
↓, ↑, ↑, ↑
Your body thinks it is starving because there is no glucose entering cells, so insulin therapy aims to __ glucose uptake
↑
___ ketone body production in diabetics can be lethal
Excess
Ketone bodies are moderately strong acids, and excess production can lead to _____. In untreated diabetics, there can be overproduction of ketone bodies, leading to ______ ______
acidosis, diabetic ketoacidosis
If insulin is absent or not functioning, glucose cannot enter cells. All energy must be derived from ____, leading to the production of _____ ___
fats, acetyl CoA
In diabetics, _______ is used for glucose production, so there is insufficient amounts to react with acetyl CoA from fatty acid oxidation. Instead, _____ __ builds up because oxaloacetate is not available to replenish the TCA cycle. Result is that acetyl CoA is utilized for ?
oxaloacetate, acetyl CoA, ketone body production
In diabetics, KB _____ > KB ______
Synthesis, Oxidation
Low fat diet still contains lots of ________: dietary _______ are broken down into glucose, _____ blood glucose levels. Insulin is secreted from pancreas and stimulates glucose _____. Promotes fat storage
carbohydrates, carbohydrates, raising, uptake
In the keto/ketogenic diet, most calories come from ___ and very little _______
fats, carbohydrates
Goal in the keto/ketogenic diet is to reduce body weight and get rid of excess triacylglycerol from adipose tissue by stimulating _____ and ? by restricting carbohydrate intake so ____ not secreted. Glucagon/epinephrine is secreted which activates lipolysis so the body’s primary fuel source shifts from _____ to ____
lipolysis, fatty acid oxidation, insulin, glucose, fat
With the keto diet, you want to stimulate _____, but not ______
ketosis, ketoacidosis
What is ketosis?
Production of ketone bodies
What is ketoacidosis?
Very high levels of ketone bodies in the blood, ↓ blood pH leads to coma, death, which can happen if not enough caloric intake is too low
In the keto diet there are beneficial metabolic changes (short-term) which does lead to weight loss, __ hunger, __ energy expenditure, __ fat loss vs protein. But there are some pitfalls: hunger, fatigue, low mood, irritability, constipation, kidney stones, nutrient deficiencies, headaches, brain “fog,” ↑ uric acid in the circulation can cause gout
↓, ↑, ↑
