Biochemistry Flashcards
what is the effect of histone ubiquitylation?
affects chromatin structure and gene transcription . effects chromosome alignment and segregation. DNA repair, transcriptional response to inflammation
how does telomerase function to solve the end replication dilemma?
contains telomeric RNA which allows it to extend the 3’ end of DNA
NADPH is an important reductant in the ….pathway
pentose phosphate pathway
DNA structure is referred to as what?
double helix
what does each enzyme in DNA replication do. Helicase, topoisomerase, primase, ligase, DNA polymerase 3 and DNA polymerase 1?
helicase - unwinds DNA
topoisomerase - nicks backbone and releases tension that results from strand separation.
Primase- lays down RNA primer. leading strand needs just one but for the lagging strand each Okazaki fragment needs one
DNA polymerase 3- elongates nucleotide chain from the RNA primers. 3-5’ exonuclease activity
DNA polymerase 1 - this has the job of removing RNA primers and replacing with DNA. enzyme has 5’-3’ exonuclease activity.
Ligase seals Nick in the backbone to join two Okazaki fragments
peptide bonds of alpha helices are aligned … to the helical axis
parallel
signals for cells to activate anabolic pathways
high NADH, high NADPH, high ATP
what repair pathway is used when there is an insertion or deletion in the DNA?
Mismatch repair pathway
what three amino acids can undergo phosphorylation.
those that contain -OH. Serine, threonine, and tyrosine
double bonds in naturally occurring double bonds are in the … configuration
cis
what role can protein phosphorylation have ?
change the affinity of a protein to a ligand or substrate. also can be a docking site for proteins
tRNA is an … molecule between mRNA and amino acids
adaptor
where is sphingomyelin abundant ?
nerve cells for transmission of impulse (action potential)
CAAT, GC and TATA are common elements of the…. of a gene? they are consensus sequences often found in the … ?
core promoter. these are regulatory sequences
GPLs are a major component of the …?
cell memrbrane
what is the property of DNA polymerase that makes it self correcting ?
3-5’ exonuclease activity. Can cleave off mis matched base pair
how many Hydrogen bonds does A T form vs C
2 and 3, respectively
strands in DNA are arranged in a … fashion?
antiparallel
what are the 3 non polar amino acids that contain an aromatic ring? what are their one letter codes
phenylalanine (F), tyrosine (Y), tryptophan (W)
mRNA binding site of the ribosome located in the …?
small subunit
what family of proteins is ubiquitinated and degraded as a result of the stage of the cell cycle
cyclins. different cyclins expressed at various stages of the cell cycle. certain cyclin is present at G1 and then is degraded as the cell moves into S phase. ensures correct progression through the cell cycle
what are the 7 roles of proteins?
transport - hemoglobin, contraction - actin, structural - collagen, hormones - TSH, enzymes, control of transcription and translation - polymerase, ribosomes, transcription factors, protection - immunoglobulins
how is pre-insulin modified to become mature insulin ?
disulphide bonds form between A and B chains. C or connecting peptide chain between A and B chains is removed
omega carbon is??
carbon furthest away from the carboxyl group
main role of triacylglycerols?
energy storage in adipose tissue
300 nm fibres are compressed and fold to form a ?
250 nm wide fibre
alpha helices have … residues per turn? are turn which way
3.6. right handed
why is a peptide bond planar ?
resonance of the amide bond. Partial bond between C of 1 residue with the N of the other residue
with the lagging strand we get … synthesis, while with eh leading strand we get … synthesis. short segments made during lagging strand synthesis are referred to as..
discontinuous. continuous. Okazaki fragments. we get discontinuous synthesis of the lagging strand because the replication fork is moving in the opposition direction of synthesis. DNA is only synthesized 5-3’
ATP can be formed via which 2 processes?
substrate level phosphorylation
oxidative phosphorylation
3’ poly a tail has the role of …?
controlling the stability of mRNA
coiling of 250nm wide fibres produces ??
chromatin
during replication a new nucleotide is attached to the … of the previous nucleotide?
3’ OH group
collagen is rich in what two amino acids ?
glycine and proline
what are the 3 stop codons
UAA, UAG,UGA - these do not have an associated amino acid
what are the three components of a nucleotide?
deoxyribose sugar, 5’ phosphate group, and 1 of 4 nitrogenous bases
RNA - protein complex that has the role of removing introns from RNA transcript?
spliceosome
this disorder is within the family of nucleotide excision repair disorders. However there is a specific defect in transcription coupled removal of thymine dimers caused by UV light.
cockayne syndrome
name the 5 most common GPLs
phosphatidyl serine, inositol, choline, ethanol amine, glycerol
RNA pol2 does what?
synthesizes all mRNA and some non-coding mRNAs
what is the main difference between deoxyribose and ribose sugars?
deoxyribose sugar has no 2’ OH group while ribose does
… is a protein that is involved in muscle contraction. It is alternatively spliced depending what tissue it is expressed in.
tropomyosin
lipids having non polar and polar properties are termed ?
amphipathic
single stranded region of the tRNA at the 3’ end has what functional role?
attaches to amino acid
Inactive/ condensed chromatin. Not exposed so hard for transcription factors to bind
heterochromatin
3’ end of DNA contains what?
hydroxyl group (-OH)
…. is required for the complete oxidation of fuel molecules and thus maximum energy extraction
oxygen
during translation the … moves 1 codon towards the 3’ end of the mRNA before the…
large subunit. small subunit
describe structure of DAG
glycerol esterified to two FAs
mode of action of imatinib?
ATP competitive inhibitor. Inhibits Bar-abl kinase capacity
which two aminos acids act as strong helix breakers.
proline - rigidity glycine - small R group supports other conformations
template strand is also called what?
antisense strand, non-coding
region spliced out during processing of primary mRNA?
intron
3 ways to control gene expression
chromatin remodelling, availability of transcription factors, stability of mRNA
what is quaternary protein?
two or more polypeptide chains binding together. can be covalent or non covalent
when ribosome encounters a stop codon in the A site, a … factor will bind this site and lead to disassociation of both ribosomal subunits from the mRNA and release of polypeptide chain
release factor
what are the two classes of protein?
fibrous (eg collagen) - these typically have one secondary structure. globular - mixter of secondary structures.
most naturally occurring Fatty acids have a .. number of carbons
even
clusters of ribosomes may sit on a mRNA transcript each actively transcribing a polypeptide. This is termed what?
polyribosome
genes beside housekeeping genes have regulated expression. expression can be 1,2,3 specific
tissue, temporal and developmental specific
biotin is linked to some enzymes via linkage to what amino acid?
lysine
miRNA binding to 3’ UTR of target mRNA can lead to …?
mRNA degradation and/or reduce translation
tRNA binds … to the mRNA codon?
antiparallel
these two disorder are characterized by defects in DNA damage response?
ataxiatelangiectasic and Li Fraumeni syndrome
DNA is always read ….?
5-3’
for the poly A tail to be added, the mRNA must first be … in the 3’ UTR
cleaved
What is the bond that holds adjacent nucleotides together?
3-5’ phosphodiester bond
the … ring of NAD+ accepts … electrons and 1 … in going to the reduced state ….
nicotinamide
2 electrons
1 proton
NADH
R groups in beta sheets protrude from the sheet in .. and .. direction
up and down
True or False. all protein products within the mitochondria are encoded by the nuclear genome?
False. The mitochondria has its own circular genome with 37 genes
growing peptide chain grows from the .. to the.. terminus ?
N to C
cyclooxygenase pathway generates ..?
prostaglandins and thromboxane - role in coagulation and inflammation
the mRNA transcript is translated in the … direction ??
5-3’ direction
how do cis bonds affect structure of lipid aggregates?
bend and pack in a less ordered way
histone proteins are … charged and DNA is … charged?
positive and negative, respectively
tRNA can have unusual bases, including … this base cannot base pair with …
inosine. G but can base pair with A, U, C
general structure of cholesterol?
3 6 membered rings. 1 5 membered ring. OH group given making it somewhat amphipathic. 8 carbon side chain
.. Box is found in many genes lacking TATA box (e.g housekeeping genes)
GC
linoleic and linolenic acid are the precurors for what? these two molecules are broadly classified as ?
arachidonic acid (ARA) and eicosapentaenoic acid (ERA) eicosanoids
chromosomes that have the Bcr-abl gene are called what?? what cancers can this lead to
philadelphia chromsome. PC+ acute lymphoblastic leukaemia and chronic myelogenous leukaemia
insoluble protein secreted in misfolded state deposits as …?
amyloid
transcription occurs in the …?
nucleus
AUG is the … codon? and it codes for what amino acid
start. methionine
oxidation means what?
loss of electrons. in practice take away electrons from C-H and replace with electrons from O
if a …. residue is at the N terminus of a peptide chain it often cyclizes
glutamate
what role does cholesterol have on membrane fluidity?
decreases membrane fluidity near the surface but acts as a spacer allowing greater fluidity deeper inside the lipid bilayer
… collagen chains come together to form a .. handed superhelical triple helix
- right handed
these channels allow for the movement of water across membranes. what organs are they most commonly expressed in
aquaporins
kidneys
besides a component of the cell membrane what roles does cholesterol have?
precursor for steroid hormones (estrogen, testosterone, cortisol, calciferol, aldosterone)
also precursor for bile acids and salts (cholic acid and deoxycholic acid)
…. with associated translation initiation factors and initiator tRNA moves along the transcript …. to find the first proper start codon (AUG)
small ribosomal subunit. 5’-3’
living systems must comply with the ….
laws of thermodynamics
structural proteins often have a high proportion of … amino acids?? and repeated … structure ?
hydrophobic. often insoluble . secondary
miRNA associates with the complex?
RISC
miRNA often binds to the … of mature mRNA and affects?
3’ UTR. mRNA translation and stability
these two amino acids are strong alpha helix formers
alanine and leucine
what is the isoelectric point?
PH when the overall net surface charge of a polyprotic macromolecule is 0
how to enzymes affect reaction kinetics?
they lower the activation energy. usually the bodies thermal energy is sufficient to overcome this.
30 nm fibers create loop structures of ??
300 nm
name two hemoglobinopathies?
sickle cell anemia and thallasemia
… is a general transcription factor that can bind to the Tata box which is 30 nucleotides upstream from transcription start site?
tata binding protein (TBP)
what causes van der waal forces?
transient dipole moments within bonds
what is a reading frame mutation?
this is an insertion or deletion of nucleotides that is not a multiple of 3. this changes all the codons downstream of the mutation. can have very serious outcome
Bcr-abl is a … kinase that is … active. what is the result?
tyrosine kinase that is constitutively active. increased cellular proliferation
what are protein domains?
modular units, often with discrete function from which larger proteins are built
roles of glycosphingolipids
nerve impulse transmission, cell-cell recognition, molecular recognition
what is the structure of sphingomyelin ? is it a glycerophospholipid or a phospholipid
ceramide by phosphorylcholine or ethanolamine esterified to C1 of sphingosine. phospholipid
organic solvents disrupt which force that stabilizes protein structure?
hydrophobic interactions
general structure of triacylglycerols.
glycerol esterified to 3 fatty acids
group disorders characterized by mutations favouring misfolded proteins
amyloidoses
what is the structure of hemoglobin? type and number of subunits and associated cofactors
4 subunits. 2 alpha and 2 beta chains. each subunit has a porphyrin molecule which conjuagates iron and is therefore able to bind oxygen
TBP after binding to the TATA box recruits … and other accessory TF2 proteins to the promoter. This complex then recruits and phosphorylates … thereby activating it.
TF2D
RNA polymerase
heat or cold disrupts what bonds that contribute to protein structure?
hydrophobic interactions and hydrogen bonds
a peptide bond is what kind of bond?
amide bond
Name 5 types of non-coding RNA and discuss role
rRNA, tRNA, SiRNA, miRNA, snRNA
when is base excision repair utilized by the cell?
oxidation of base, introduction of uracil, abasic site, single stranded break
RNA pol3 does what?
synthesizes mtRNA
what is often found in beta turns
proline in position 2 or glycine in position 3
what are 2 essential unsaturated fatty acids ?
linoleic acid (C18:2, omega 6) , linolenic acid (C18:3, omega 3)
patients with xeroderma pigmentosum have the inability to resolve …. caused by UV light
thymine dimers
the gamma carbon of glutamate can undergo what modification?
gamma carboxyglutamate - now has 2 carboxyl groups. this is important for clotting factors to be able to bind Ca2+
endergonic processes can be driven by …. to …. processes
coupling
exergonic
define positive cooperativity in regard to oxygen bindin hemoglobin?
once one O2 binds hemoglobin it becomes easier for the 2nd O2 to bind. And this relationship continues
non-template strand is also called what?
sense strand or coding
what are the 3 amino acids with positively charged R groups and what is their 1 letter code..
lysine (K), arginine (R), Histidine (H)
many … reactions are coupled to the exergonic hydrolysis of ATP. The overall free energy change is now
endergonic
negaticve
sequence recognized as initiator sequence of translation containing AUG and other consensus sequence is termed ??
Kozaks sequence
only … amino acids are found in nature ?
L
what is the most common role of ubiquitination ? what amino acid is commonly ubiquitnated ?
target protein for proteosomal degradation. lysine
three key energy generation pathways occur in the mitochondria?
beta oxidation, TCA cycle and oxidative phosphorylation
the genetic code is termed .. ? multiple codons code for the same amino acid
degenerate
virtually all peptide exist in a … configuration?
trans. alpha carbons of adjacent residues are on different sides of the peptide bond
what are 2 common secondary protein structures?
alpha helix and beta sheets
this element comprises 30-40% of the cell membrane? and what role does it have?
cholesterol
regulates membrane fluidity
describe the structure of a typical chromosome?
p arm - this is the short arm (think petite). Q arm - long arm. centromere. telomeres - ends of the chromosome
what is the name of the glycosphingolipid that has ceramic conjugated to one of galactose or glucose
cerebroside
another word for biosynthesis
anabolism
the majority of people with HNPCC have a mutation in what protein?
MLH1
what enzyme allows replication of the ends of chromosomes. Is it present in all cells ?
telomerase. no it is not present in every cell. mostly expressed undifferentiated stem cells and cancer cells.
why are GC rich regions in DNA harder to separate than AT rich regions?
G base pairing with C contains 1 more hydrogen bond than AT
DNA and associated proteins fold and pack the DNA into a more compact structure called ?
chromatin
during translation. the … end of the polypeptide chain is uncoupled from the tRNA at the … site and joined by a peptide bond to the free … group of the amino acid linked the tRNA in the A site
carboxyl, P site, amino group
what are key proteins in the MMR pathway?
MLH1, MLH2, MSH6 and PMS2
if a mismatch in DNA is not correct by DNA polymerase what repair system does the cell utilize to correct it ?
mismatch repair system
what is the delta G of exergonic reactions? are they spontaneous
less than 0. Yes
what is the fatty acid C18:0
stearic acid
antagonistic metabolic pathways are … regulated
co-ordinately regulated. when one is on, the other Is off
- beta oxidation and fatty acid synthesis
3 events that take place to form mature mRNA from the primary transcript?
Splicing of introns, add 5’ methylguanosine cap, and 3’ polyadenylation tail (polA tail)
what is unique about proline? what consequences does this have when incorporated into a polypeptide
R group forms a cyclic structure with the amino group. this adds rigidity to the structure
what are two common motifs in the amino acid sequence of collagen ?
glycine-proline-X.
glycine-X-hydroxyproline
why does a small electric dipole exist within the peptide bond?
because of resonance the O has a partial negative charge and the N has a partial positive charge
lipooxygenase pathway produces what? and these are important for what?
leukotrienes. inflammatory response
glycerophospolipids are derived from which basic compound
phosphatidate. glycerol esterified to 2 fatty acids. 3 carbon is linked to a phosphate group
when is base excision repair used? and how can these DNA modification be made
intrastrand crosslink and bulky adducts. UV light and polycyclic aromatic compounds
this family of enzymes breaks down GPL
phospholipase
this is disorder is characterized by defects in repair of interstrand crosslink. patients have increased pigmentation, abnormalities in the skeleton, heart, kidneys and predisposition to leukaemia ?
Fanconi anemia
what are the two properties of DNA polymerase that allow it to replicate DNA with high fidelity ?
highly accurate 5-3’ polymerizing activity
3-5’ exonuclease activity - gives enzyme intrinsic proofreading
RNA pol1 does what?
synthesizes rRNA
resonance in peptide bond means what?
is less reactive than a ester, quite rigid and planar, exhibit dipole moment in trans configuration
estrogen bound to its receptor function as a … and must bind to its …. within the distal promoter
transcription factor. response element
because anabolism is endergonic it must be coupled to… for it to be favourable?
ATP hydrolysis
are oxidation reactions exergonic or endergonic?
exergonic
components of a nucleoside?
sugar + nitrogenous base
catabolism is the … of fuel molecules
oxidation
what family of proteins is responsible for addition of phosphate group to a protein ? what family removes phosphate groups
kinases
phosphates
which class of immunoglobulins is able to cross the placenta ?
IgG
hydrolysis of the …. bonds of ATP releases a large amount of energy.
phosphoanhydride
transcriptional activators can recruit … which modify residues of the histone N terminal tails which alters chromatin structure
chromatin remodelling complex (histone acetylases)
industrial production of unsaturated fatty acids yields C_C double bonds in the … configuration
trans
what histone proteins make up the histone core?
H2A, H2B, H3, H4
what is the role of splicing ?
to increase the number of proteins from a limited number of genes
metabolic pathways must be … favourable??
energetically favourable
catabolic and anabolic pathways are distinct allowing both to be … favourable, and … independently
energetically favourable
controlled
essential fatty acids have a C-C double bond that is beyond …?
carbon 9
what is molecule are most glycosphingolipds derived from ?
ceramide
modification of histones and DNA that do not alter the DNA sequence but may alter its ability to be expressed.(alters chromatin structure)
Epigenetic modifications
what are 4 important coenzymes that are often required for redox reactions?
NADH, NADPH, FADH2, FMNH2
what is the minimum contact distance (van der Waals contact distance )?
distance less than this repulsion is favoured. distance greater attraction is favoured.
consensus sequence for introns. They start with … and end with ..
GU and AG
In a karyotype, what stage of mitosis are the cells usually viewed in?
metaphase - 2n 4C
DNA polymerase has .. activity which allows it to remove the RNA primers.
5-3’ exonuclease activity
what is a nucleosome? and what are the components
most fundamental unit of DNA packaging. consists of a central core of 8 histone proteins
what bond do lipase cleave?
ester bonds between fatty acids and glycerol
do exergonic reactions favour the reactants or products at equilibrium ? is the Keqilibrium less than or greater than 1
products. Greater
what is the distinct property that cysteine has?
has the ability to form disulphide bonds with other cysteine residues
what are the genetic predisposition to HNPCC
mutation to any one of the genes that codes for a protein involved in the mismatch repair pathway.
when are double strand break repair pathways used? HR and NHEJ
double strand breaks and interstrand crosslink. Intrastrand uses numerous pathways but homologous recombination is one of them
what is pharmacogenomics?
this is the study of the genetic composition of an individual to health identify there response for a given therapeutic
why is the pKA of the histidine R group? why is this relevant to human biochemistry
- This has the ability to be protonated and deprotonated under physiological conditions. often in the active site of enzymes as a proton donor and acceptor
result of transcription is an .. molecule with sequence identical to the … DNA strand but with..
mRNA. coding/nontemplate/sense strand. U instead of T
transcriptional activators can bind to … sequences (distal to the promoter) and interact with DNA of the promoter through DNA looping.
enhancer, DNA looping
what is the molecular force that holds two strands of complementary DNA together?
hydrogen bond
this inherited disorder is characterized by sun sensitivity. individuals may get freckling and subsequent neoplastic changes. patients have a defect in nucleotide excision repair.
xeroderma pigmentosum
anabolism is typically … and … in nature?
endergonic and reductive.
describe what a ganglioside is ?
glycosphingolipid (GSL) - 3 or more sugars , one of which is NANA ( N acetylneuraminic acid)
DNA sequence that contains the coding information for that protein?
exon
neurodegenerative disease that are characterized by amyloidosis
huntingtons, Parkinson’s, and Alzheimers
what enzyme allows replication of the ends of chromosomes
telomerase
regulation of the activity of the … enzyme in a metabolic pathway controls the metabolic flux through the pathway
rate limiting enzyme. irreversible committed step
forces involved in tertiary structure of proteins?
van der waal forces, ionic, disulphide bonds, hydrogen bonds
lysine is know to undergo which modifications?
hydroxylation, acetylation (histones), and methylation, ubiquitnylation
3 forces that drive protein folding ?
hydrogen bonds, van der waal forces, and ionic bonds
fatty acid aggregation with one layer is called a ??
micelle
name 2 common chaperon proteins and 2 other proteins that aid in protein foldin?
HSPs and chaperoning. peptidyl propel cis trans isomerase and disulphide isomerase
how does a lack of vitamin C (ascorbate) contribute to impaired collagen formation. what is this condition known as
can’t form hydroxyproline. scurvy
what are CDRs of immunoglobulins. what is there role?
complementary determining regions. gives specificity for what antigen the AB will bind to
DNA with 42% GC Composition - what are the individual base composition?
21% for G and also C.
29% for A and T individually
origins of replication are typically … rich? why?
AT rich. these have only 2 hydrogen bonds while GC base pairs have 3 hydrogen bonds
What is the exome?
part of the genome composed of exons. These are sequences that remain with the mature mRNA and can be translated in a polypeptide chain
5’ cap functions to ? 1) protect from… 2) facilitates .. from the nucleus to the cytoplasm 3) .. for translation
5’ exonuclease, transport, start signal
replication occurs in a … manner from the origin of replication?
bidirectional
differences between RNA and DNA
RNA contains uracil instead of thymine. this base pairs also with adenine. RNA is typically single stranded (see exceptions with structure such as tRNA and primary miRNA)
during transcription, the DNA is read … and the mRNA is transcribed…?
3 -5’. 5-3’
epigenetic modifications of histones include. (4 of them)
acetylation, methylation and phosphorylation and ubiquitination
these two disease are often a result of splice site mutations?
neurofibromatosis 1 and Menkes disease (increased copper in the body)
chaotropic agents such as urea and guanidium hydrochloride disrupt which force that stabilizes protein structure?
hydrogen bonds
what protein domain binds to phosphotyrosines?
SH2
what is the fatty acid C16:0
palmitic acid
this is a disorder caused by defects in nucleotide excision repair. patients have brittle hair, short stature, immature sexual development and skin abnormalities.
trichothiodystrophy
protein sequencing done by cleaving amino acids one by one from the end and sequencing each amino acid ?
Sanger sequencing
nucleosomes fold up to produce a ??
30 nm fiber
this enzyme separates the two strands of DNA during transcription ?
helices
Because DNA replication uses both strands of the parent DNA to ultimately 2 identical copies of DNA, it is termed ?
semi conservative
many collagen triple helices assemble into a collagen…?
fibril
humans chromosomes are usually studied in what type of cells ?
Dividing cells - e.g cultured T lymphocytes, skin fibroblast, fetal cells of amniotic fluid or chorionic villi
trans fatty acids can lead to an increase in … cholesterol
LDL
signals for cells to activate catabolic pathways
low NADH, low NADPH, low ATP to ADP ratio
what is the role of the centromere?
attachment site of sister chromatids. During mitosis, the mitotic spindle attaches here and allows each chromatid to be pulled towards opposing poles
describe why the wobble hypothesis exists?
61 codons exist that code for a specific amino acid. There is not 61 different tRNA. The 3rd bae is less discriminatory than the other 2 bases therefore all codons can be accommodated with a tRNA
if something is reduced, it is the … agent
oxidizing agent
Bcr-abl is a … gene?
fusion
main roles of lipids?
structural aspect of the cell membrane, energy reserves (TGs), vitamins and hormones, bile acids for lipid solubilization, biological signalling molecules (DAG)
what are the main roles of post translational modification?
can direct protein to a specific location (RAS protein gets a lipid tail added on for localization to the plasma membrane), influence protein activity, influence interaction with other proteins, control protein stability
human metabolic storage disorders characterize]d by the accumulation of harmful quantities of glycosphingolipids and phosphosphingolipids. what organelle and associated enzymes is not working in patients with one of these disorders
sphinolipidoses. lysosomal storage disease - eg tay Sachs disease
true or false. tertiary protein structure is determined by the primary sequence but may require additional chaperone proteins and accessory enzymes
true
what does hydroxyproline in collagen chain contribute to the formation of triple helical collagen ?
offers more hydrogen bonds
during DNA replication the enzyme… adds a new nucleotide to the free … of the DNA strand
DNA polymerase. 3’ OH
name of the bond formed between sugar and base of a nucleotide ?
N-glycosidic bond
what is the main take home message from the ribonuclease experiment in regard to protein folding?
protein denatured by addition of 2-mercaptoethanol (reduces disulphide bonds) and urea. when these agents were removed, the protein spontaneously refolded to native conformation. sequence alone determines the shape of a protein
true or false. MMR pathway uses non-template strand for reference to correct mismatch?
false. non-template is the newly synthesized strand. It will
if the PH is less than the PKA, what does that mean for the protonation state of that group?
it is protonated. if PH is greater than PKA then that group is deprotonated
aspirin is an inhibitor of … enzyme
cyclooxyrgenase enzyme
immunoglobulins consist of 2 … and 2..?
light chains
heavy chains
why is formation of triacylglycerols an efficient way to store energy? more so than glycogen
because fatty acids have been esterified to glycerol they are no longer hydrophilic. no salvation shell is required. glycogen needs a salvation shell (polar)
describe how DNA has polarity?
the ends of DNA are not identical - 3’ OH and 5’ phosphate of each end are not symmetrical to the other end of the DNA strand
what is the beta turn stabilized by?
hydrogen from carbonyl to amide three residues down
GPLs are a major component of the …?
cell membrane
what do chromosomes include?
DNA and associated proteins
what are the components of ceramide?
sphingosine + fatty acid attached to the amino group of C2 of sphingosine (amide bond)
pH extremes disrupt which stabilizing force of protein structure?
ionic bonds
many collagen fibrils come together to form a collagen…?
fiber
name the 5 most common GPLs
phosphatidyl serine, inositol, choline, ethanolamine, glycerol
active/ open chromatin that can be transcribed easily
euchromatin
what principal describes the fact that equilibrium can change if products or reactants are altered
le chataliers principle
region of tRNA that can complementary base pair (with exception) to the codon of the mRNA
anticodon
what is required for the formation of hydroxyproline?
prolly hydroxylase, alpha-ketoglutarate, and ascorbate (vitamin C)
True or false. Approximately 1% of the human genome is protein encoding
True
what cell type has no nuclear DNA?
Red blood cell
what are the two roles of DNA?
Transmit and store information – transmit to identical daughter cells in the case of mitosis or to haploid gametes in meiosis
what is HNPCC?
hereditary non polyposis colon cancer. inherited tendency to develop colon and other associated cancers (80% chance)
H1 histone interacts with DNA located in the … region. DNA between the DNA that interacts with the core histone proteins.
linker region
some proteins once translated have there N terminal methionine and maybe some additional amino acids cleaved off. This is achieved via the action of ?
N terminal methionine aminopeptidases
2 groups of nitrogenous bases and what is there difference ?
Purines (A,G) - double ringed structure and pyrimidines (C,T) - single ringed structure
what are the 5 main classes of lipids ?
fatty acids
triglycerides
glycerol phospholipids
sphingolipids
cholesterol
proteins fold into a conformation of … ? this is determined from the … sequence
lowest energy. primary
dwarfism, sensitivity to sunlight, premature aging, deafness and mental retardation or symtoms of what disorder?
cockayne syndrome
in sickle cell anemia a point mutation causes a glutamic acid to become a …? what is the effect of this mutation
valine. this causes beta chains to stick together. repellent force of glutamic acid with other glutamic acids is gone.
which two histone core proteins are ubiquitinated ?
H2A and H2B
beta turns are accomplished over … residues ?
4
globoside is ceramide + ….
2 or more sugars, not including NANA
what has been the 3 results of genetic advances in healthcare?
Cancer diagnosis and treatment, Non invasive prenatal screening, personalized medicine which includes pharmacogenomics
this protein is found in muscle cells and binds oxygen. it has 1 subunit unlike another protein that binds oxygen .
myoglobin
… tails of core histones protrude from the nucleosome ? what specific amino acid is modified here ?
N terminal. Lysine. This effects how the chromatin is packed
partial proteolysis is an example of a protein modification. what protein undergoes this?
Insulin. C chain is cleaved out
A and B chains now only connected via disulphide bonds
name 4 pathways that can be utilized to repair DNA
mismatch repair pathway, base excision repair, nucleotide excision repair, double stranded break repair (non homologous end joining or homologous recombination)
in humans … energy released by chemical reactions is transducer into … energy and this is used to drive the energy requiring process of the cell
free energy
chemical energy
allosteric regulation refers to…
binding of an effector molecule to an enzyme not at the active site
what force/s are secondary protein structures stabilized by? what atoms are involved
hydrogen bonds only. only main chain atoms are involved. R groups are not involved
triglycerides are … % of dietary lipid consumption
90%
… are amphipathic lipids which act as biological detergents and emulsify lipids
what are the names of the 3 lipases that the bodies utilizes in digestion of triglycerides?
lipase cleave …. bonds between glycerol and fatty acids
ester
bile acids are synthesized in the …. and stored in the …?
bile salts are more … and less … compared to bile acids
the vast majority of bile salts are not excreted but rather … in the … of the GI tract
rebaorbed
ileum
bile salts are derived from which class of lipids
process by which large lipids droplets disperse into smaller ones. This increases the surface area
this protein anchors pancreatic lipase to the water-lipid interface and prevents lipase from being washed away by bile salts
Orlistat /xenical is an inhibitor of what enzyme
side effects of increased lipid retention in the gut
break down of lipids in the small intestine leads to the formation of mixed ….?
contents of mixed micelles ?
during lipid absorption. … and … can enter enterocytes via passive diffusion. … and … can enter enterocytes via facilitated diffusion
free fatty acids, cholesterol, DAG, MAG are utilized within the enterocytes to resynthsize what?? This occurs where within the cell
triacylglycerols, cholesterol esters, phospholipids
smooth endoplasmic reticuluum
… consist of lipids packaged with apolipoproteins, derived from enterocytes
true or false. chylomicrons first enter blood circulation?
free glycerol absorbed in enterocytes and not reconstituted with fatty acids to make TAGs can directly enter?
blood circulation
plant sterols can be used to block … absorpotion? they compete with … for incorporation into mixed…? plant sterols are however not… into enterocytes
cholesterol
cholesterol
micelles
TAG are too … to be digested and absorbed. they must be … by bile salts and broke down to … , …. and …
hydrophobic
solubilized
MAGs, DAGs and freet fatty acids
the core of lipoproteins consists primarily of … and …. . why are they found here
triglycerides
‘skin’ of lipoproteins primarily constains … , … , and …. 2 of these are lipid deriviatievs, why can they be found here ?
phospholipids
cholesterol esters
apolipoproteins
LDL are not made in the liver but evolve from ….
VLDL
order the lipoproteins from largest to smallest. from going from largest to smallest there is an increase in ….?
chylomicrons, VLDL, IDL, LDL, HDL
these two lipoproteins are the main carriers of triglycerides ?
chylomicrons and VLDL
ApoB-100 has what function?
binds to LDL receptor on cells and allows uptake of lipoprotein
what is the main function of ApoC-2
binds to and activates lipoprotein lipase, which is required for the breakdown of TAGs
nascent chylomicrons contain Apo.. but acquire additional Apos… from HDL
B48
A,C,E
major function of chylomicron is to transport dietary … from the intestine to tissues. what tissues specifically?
TAGs
skeletal and cardiac muscle, lactating mammary glands, liver and adipose tissue
… breaks down TAGs contained in lipoproteins so they can be taken up by cells
LPLs
LPLs are found on the … surface of … cells. They are linked to these cells via …
luminal
endothelial cells
proteoglycans
Insulin activates lipoprotein lipase isoforms on endothelial cells of … tissue.
adipose tissue
… activates lipoprotein lipase isoforms located on the endothelial surface of … tissue
muscle (skeletal and cardiac)
TAG hydrolysis of chylomicrons reduces … and increases … of lipoprotein. now we have a …
size
density
chylomicron remnant
chylomicrons remnants are taken up by the liver via …. . this requires Apo… which binds to which receptor on hepatocytes ?
receptor mediated endocytosis
ApoE
LDLR family
… transports endogenous products, whereas..transport exogenous (dietary) products.
VLDL
chylomicrons
VLDL mainly transport … from liver to adipose tissue for … or peripheral tissue (cardiac and skeletal muscle) for …
TAGs
storage
utilization
VLDL TAGs hydrolyzed by … forming VLDL … (also called …)
LPLs
remnants
IDL
50% of VLDL remnants (IDL) recycle in the … (requires Apo..). Remainder converted to …
liver
apoE
LDL
LDL formed from … after … content of IDL enriched (and … content depleted). this occurs via exchange with …
IDL
cholsterol/cholsterol ester
triglyceride
HDL
Apo… is critical to function of LDL
B-100
LDL is a major … carrier to peripheral tissue
cholesterol
which peripheral tissues require cholsterol?
adrenal gland for the production of steroid hormones - cortisol, aldosteron
gonads - testosterone and estradiol ( steroid hormones)
what are the major function of HDLs?
transport cholesterol from tissues to the liver
source of numerous apoliproteins
also associarted with other proteins (LCAT, PTLP)
… is an autosomal dominant disorder that leads to grossly elevated LDL. … receptor absent or impaired or can also be caused by Apo… deficits.
familial hypercholesterolemia
LDL
ApoB-100
these are cholesterol deposits in the skin or joints. what inherited disorder is know to cause these?
cutaneous or articual xanthomas
familial hypercholesterolemia
… are used to lower levels of LDL cholsterol. They work by inhibiting endogenous sysnthesis of cholesterol in the liver
statins
what are 4 intervents to treat elevated LDL cholesterol. what is their mode of action
statins
bile acid sequestrants - prevent reabsorption of bile acids in the ileum
LDL apheresis -
excess plasma LDL can accumulate in the … of blood vessels. LDL can then be oxidized which is a pro… signal.
intima
inflammatory
macrophages take up oxLDL by a … mechanism. This leads to macrophages to become … cells and generate … streak
scavenger receptor
foam
fatty
TAGs are a more efficeient way to store as they do not require a … shell.
a gram of triglycerides has … times more energy than 1 g of glycogen
solvation
2
what pathways does the cell need products from the synthesize fatty acids?
NADPH from PPP
NADPH from the citrate shuttle
acetyl coa- from the citrate shuttle also
reference to citrate shuttle. pyruvate in the mitochondria can be used to make … and …. these two products combine to form…. this is then secreted into the cytosol. … is broken down to … and ……
… is a building block of fatty acid synthesis and the other is mdae into malate. male is then oxidized to produce pyruvate and …
acetyl coa and oxaloacetate
citrate
acetyl coa and oxaloacetate
acetyl coa
NADPH
Fatty acid synthesis is utilized for .. storage in time of
energy
excess
… and .. are major sites of fatty acid synthesis
… tissue is main site of energy storage
liver and mammary gland
adipose
in fatty acid synthesis acetyl coa (2C) is converted to … (3C)
malonyl
fatty acid chains are elongated by the sequential addition of … carbon units from … in a series of 4 reactions (what are these 4 reactions??)
2
malnoyl coa
condensation, reduction, dehydration, reduction
elongation of fatty acid chains continues until the Fatty acid chain is … carbons in length. further elongation and desaturation requires an alternative set of …
16 (palmitic acid)
enzymes
humans cannot introduce double bonds after Carbon …. this is why we need to consume essential fatty acids (what are the two metioned essential fatty acids ?)
9
linoleic and linolenic acid
acetyl coA cannot be directly transported into the cytosol from the mitochondria. what is the solution ?
citrate shuttle
most acetyl coa is generated in the mitochondria via … enzyme (prelude to TCA cycle) and … of fatty acids
pyruvate dehydrogenase
beta oxidation
the citrate shuttle generates 1 … but costs 1 …
NADPH
ATP
citrate is the first intermediate in the …
if there is high levels of citrate in the cell what does this signify?
TCA cycle
increased energy in the cell and high flux through the TCA cycle
this enzyme is responsible for the formation of malonyl coa from acetyl coA.
what cofactor does this enzyme require
acetyl coa carboxylase (ACC)
biotin
formation of malonyl coa during fatty acid synthesis represents the … … step in fatty acid synthesis. This is because this reaction is highly … because it is coupled to … hydrolysis
rate limiting
exergonic
ATP
Acyl carrier protein is attached to reaction intermediates of fatty acid synthesis via the … group of phosphopantetheine
thiol (-SH)
in terms of function ACP is like a large ….
fatty acid synthase is a … complex
multienzyme
FAS has … distinct enzyme activities
5
the first step of fatty acid synthesis involves the transfer of the acetyl group of acetyl coa to …. which is catalyzed by …
also malnoyl coa is attached to ACP by
Beta-ketoacyl-ACP synthase (KS)
MAT
MAT
the first reaction of fatty acid synthesis involves the condensation of 2C … unit and 3C … unit with loss of …
this reaction is catalyzed by
acetyl
malonyl
b-ketoacyl-ACP synthase
elongation of fatty acid chain after generation of 4 carbon butyrl ACP.
Butryl is transfered to … and …. is transferred onto ACP
this is achieved by the enzyme …
b-ketoacyl-ACP- synthase (KS)
malonyl unit of malnoyl coa
MAT
palmitate the major end product of fatty acid synthesis is cleaved from ACP by …
thioesterase
fill in the coefficnets for the synthesis of palmitate
Acetyl coA + malonyl coA + NADPH + H+ —– palmitate + CO2 + NADP+ + coA + H20
1, 7, 14, 20, 1, 7,14, 8,6
synthesis of malonyl coa (7 of them)
write out the reaction
7 acetyl coa + 7CO2 + 7ATP —– 7 malonyl coA + 7ADP + 7Pi + 14H+
of the 14 NADPH required for the synthesis of palmitate, 8 are from the …. and 6 are from ….
how many ATP are required in total to synthesis citrate
citrate shuttle (costs 1 ATP per NADPH)
Pentose Phsophate pathway (costs 3 ATP)
18 (7 to make malonyl coA)
elongation of palmitate does not occur in the cytosol unlike sysnthesis of palmitate itself. where else does it occur ?
endoplasmic reticuulum and mitochondria
where does fatty acid desaturation take place? what are the enzymes referred to as ?
endoplasmic reticuluum
desaturases
what is the key control point in fatty acid synthesis ?
transformation of acetyl coa to malonyl coa via action of ACC (acetyla coA carboxylase)
how does malonyl coA inhibit beta-oxidation ?
inhibits the enzyme carnitine transferase. carnitine added to fatty acids allows them to move into the mitochondria where beta oxidation occurs
- this is inhibited when there is high levels of malonyl coA
acetyl coa carboxylase (ACC) is subject to …. regulation and reversible … modification
allosteric
covalent (phosphorylation)
monomeric ACC is … while polyermic filamentous ACC is …
inactive
active
palmitoyl-coA is a … allosteric regulator of…
negative
Acetyl coa carboxylase
…. is a positive allosteric regulator of ACC activity. it signals energy abundance within the cell
citrate
regulatory effects of … and … on ACC activity or dependent on the …. state of the enzyme
palmitoyl - coA
citrate
phosphorylation
phosphorylation of ACC by …. causes the enzyme to be…
which hormone activates the enzyme that phosphorylates ACC
AMP - activated protein kinase
inactive
glucagon
…. under the control of which hormone … dephosphorylates ACC and leads it to be active
protein phosphatase 2 A
insulin - signals energy abundance
PPARS (peroxisome proliferator activated reecptors) play essential roles in ….
cell differentiation, inflammation and metabolism
endogenous PPAR ligands are mostly …
polyunsaturated fatty acids
eicosanoids
PPARS once bound by ligand form heterodimers with … and bind promoter elements of target genes
LXR receptor
once are the main consequences of PPAR activation ? what effect does this have for diabetes (type 2)
increase insulin sensitivity, lower fatty acid, triglyceride and cholesterol levels
tries to switch energy utiization from primarily lipid based to carbohydrate
what are thiazolidines? in which disease is this drug most commonly used in
PPAR gamma agonist
type 2 diabetes
what are the beneficial insulin sensitizing actions of thiazolidines?
increase glut 4 expression
dcrease TNF alpha, resistin, and IL-6
-last 3 decrease increase insulin resistance typically
what is the overall beneficial metabolic action of thiazolidines?
net transfer of TAGs to adipose tissue
what effects does PPAR gamma agonist have on the liver?
decrease gluconeogensis
decrease beta oxidation
increase glucose utilization
PPAR gamma agonist have what effect on muscle tissue?
decrease transport of fatty acid transport into them
decrease fatty acid oxidation
increase glucose utilization
C75 has dual function. it is an inhibitor of … and an acvtivator of…
Fatty acid synthase (FAS)
carnitine palmitoyltransferase
tricostan is a … which inhibits … one of the enzymes of the Fatty acid synthase multienzyme complex
broad spectrum antibiotic
enoyl ACP reductase (ER)
C75 has shown to not only decrease fatty acid synthesis but also elicits effects in the … where it promotes anorexigenic pathways and decreases orexigenic pathways
hypothalamus
inhibitors of Acetyl coa carboxylase are used as a therapeutic to treat…
in adipose tissue these inhibitors have what effect
in muscle cells these inhibitors have what effect
obesity
inhibit fatty acid synthesis
decrease malonyl coa and there promote beta oxidation
also have insulin sensitive effects
main sites of triglyceride synthesis
where in the cell does this occur
intestine, adipose and liver
mitochondria, ER and peroxisome
in triacylglycerol synthesis where is glycerol-3-phosphate derived from?
G-3-P is an intermediate of glycolysis
in the liver glycerol can be phosphorylated by glycerol kinase
what are the 4 steps of Triacylglycerol synthesis?
1) generation of G-3P
2) sequential addition of 2 fatty acid chain
3) dephosphorylation
4) addition of third fatty acid chain
what is the purpose of triglyceride synthesis in the liver? what is the purpose of TAG synthesis in adipose ?
for distribution purposes
for storage
true or false? muscle cells can do fatty acid synthase because they express the enzyme fatty acid synthase
false - do not express enzyme
Lipases cleave … bonds of …. ??
ester
triglycerides
60-80% of energy needs of mammalian … and …. muscle … …. are met by beta oxidation
cardiac muscle
skeletal muscle
liver
kidneys
Liver is an important site of fatty acid metabolism. this includes … … and … synthesis for distribution to other tissues (incorporated into VLDL) ?
oxidation of FAs for energy
synthesis of FAs for energy storage
Triglycerides
Insulin …. lipolysis in the adipose tissue
inhibits
glucagon … lipolysis in the adipose tissue which generates … and … which can be taken up by the …
stimulates
non-esterified free fatty acids
triglycerides
liver
…. and … stimulate lipolysis in the adipose tissue.
glucagon
norepinephrine
… is released in response to low glucose in the plasma. This will stimulate lipolysis in the adipose tissue. fatty acid will be used in the liver to generate ATP which can fuel …. to increase blood glucose levels
glucagon
gluconeogenesis
glucagon and norepinephrine active this enzyme in adipose tissue which acts to release free fatty acids and glycerol from triglyceride stores.
hormone sensitive lipase
… inhibits the action of hormone sensitive lipase within adipocytes.
insulin
glucagon and norepinephrine bind to this transmembrane receptor on target cells ? this leads to the activation of … which enzyme that catalyzes the cyclicization of … to … which goes on to activate which kinase??
G-coupled protein receptor (GPCR)
adenyl cyclase
ATP
cAMP
protein kinase A.
protein kinase A (PKA) phosphorylates … in adipose cells thereby activating it leading to the breakdown of triglycerides .
hormone sensitive lipase
Protein kinase A phosphorylates hormone sensitive lipase and … in adipocytes.
… is a lipid droplet protein and phgosphprylation of it is essential for mobilization of triacylglcerol
peripilin
Free fatty acids once released from adipocytes bind … in blood plasma which allows them to be soluble in circulation.
serum albumin
glycerol that has been released from adipocytes can be taken up by hepatocytes.
within hepatocytes glycerol can be used for … through conversion to pyrvate and/or … through conversion to glucose
glycolsysis
gluconeogenesis
glycerol and/or fatty acids can also be used for complex lipid synthesis including … and …
glycerophospholipids
sphingolipds
beta oxidation occurs in the … of the cell
mitochondrial matrix
during beta oxidation fatty acids are activated by linkage to …
Coenzyme A
each cycle of beta oxidation removes … carbons and generates 1 … and 1 …
2 carbons
NADH
FADH2
synthesis of Fatty acids occurs in the … while oxidation of fatty acids occurs in the … this serves to … the 2 pathways
cytosol
mitochondria
compartmentalize
Inorder to activate fatty acids for beta oxidation they must be joined to …. which is catalyzed by … and requires 1 … to drive this naturally endergonic rxn
CoA
acyl-CoA synthestase
ATP
acyl-CoA synthetase is located …
on the outer mitochondrial membrane facing the cytosol
during beta oxidation how are short chain acyl-coa molecules transported into the mitochondrial matrix? what constitues a short chain fatty acyl chain
they can freely diffuse across the 2 membranes of the mitochondria
less than 12 carbons
fatty acl coa molecules greater than 12 carbons transport into the mitochondrial matrix for beta oxidation.
step 1- remove .. and attach … to fatty acid
step 2 - transporter can move … into the mitochondrial matrix
step 3 - when in the mitochondrial matrix … is removed and … is added to the fatty acid
CoA
carnitine
acyl carnitine
carnitine
CoA
4 rxns involved in each cycle of beta oxidation ?
oxidation,
hydration,
oxidation,
cleavage
each cycle of beta oxidation generates 1 … and 1 … both of which are high energy electron carriers
NADH
FADH2
… deficiency or deficiency its associated enzyme …. can impair movement of acyl coa (longer than 12 carbons) into the mitochondrial matrix
carnitine
carnitine acyl transferase
what are the causes of carnitine deficiency (3 of them) This molecule is attached to fatty acids greater than … carbons to allow transport into the mitcochondrial matrix
dietary deficiency
impaired liver synthesis
impaired renal reabsorption
what are the clinical metabolic manifestations of carnitine or carnitine acyl transferase deficiency (2) ?
hypoketotic - ketone bodies derived from acetyl coa which is the product of beta oxidation.
hypoglycemia - need ATP from beta oxidation to fuel gluconeogenesis. also cells like muscle, kidney and liver cannot use fatty acids for energy so they must consume glucose from circulation
what ar the multisystem complications of carnitine or carnitine acyl transferase deficiency ?
affects CNS, liver, skeleta and cardiac muscle
organomegaly - increased fat deposition
myopathies
treatments for carnitine defiency or carnitine acyl transferase deficiency?
what should patients avoid (2)?
oral carnitine
dietary supplementation with short chain fatty acids - these do not need to have carnitine attached to move into the matrix of the mitochondria
high carbohydrate and low fat diet - carbohydrates are the main source of energy
avoid fasting
strenous exercise
reaction 1 of the beta oxidation is a … reaction ?
this is catalyzed by which enzyme
oxidation
acyl-CoA dehydrogenase
there are … isoforms of acyl-CoA dehydrogenase and each acts on different …. length fatty acl-CoA
3 - long, medium and short
lengths
reaction product of acyl CoA dehydrogenase generates a double bond in the … configuration
trans
what disorder is reffered to in short as MCAD?
what is the inheritance pattern
medium chain acyl CoA dehyrodgenase deficiency
autosomal recessive
what is the biochemical profile of medium chain acyl-CoA dehydrogenase deficiency? (3)
intermittent hyoglycemia
intolerance to prolonged fasting - fatqiue/lethargy
medium chain dicrboxylic aciduria - by product of an alternative oxidative pathway of medium chain fatty acids
is there alternative pathway for oxidation of medium chain fatty acids to beta oxidation ? if so what can the byproduct of this pathway lead to
yes
medium chain dicarboxylic aciduria
why are the physiological effects of MCAD severe?
medium chain fatty acids are the bulk of what we consume
how many cycles of beta oxidation are involved in the complete oxidation of palmitic acid ? what are the products of the complete oxidation?
does complete oxidation of palmitic acid require energy require energy input if so how much?
7 cycles
8 acetyl coa
7 NADH
7 FADH2
yes, activation of palmitic acid to palmitoyl CoA
FADH2 and NADH generated from fatty acid oxidation can…
donate electrons to the electron transport chain and therefore be used to generate ATP by oxidative phosphorylation
complete oxidation of palmitic acid can ultimtaley generate how many ATP? whereas 1 molecule of glucose can generate … ATP
108
32
Beta oxidation of uneven numbered carbon fatty acids.
undergo beta oxidation until … carbons remain, this fatty acyl linked to CoA is called ???
…. is then carboxylated to become a 4 carbon fatty acyl CoA molecule called? this molecule is an intermediate of the … cycle
3
propionlyl CoA
Propionyl CoA
Succinyl CoA
TCA
Oxidation of MUFAs and PUFAs requires additionals… that are not required for oxidation of saturated fatty acid
… double bonds are a substrate for beta oxidation not … double bonds
this enzyme converts cis double bonds of MUFAs and PUFAs to trans configuration
this enzyme reduces a trans + cis configuration to just a single trans isomer
after the action of these enzymes occur beta oxidation can resume as normal
enzymes
trans, Cis
enoyl CoA isomerase
2,4- dienoyl CoA reductase
where does the inital oxidation of very long or branched Fatty acids occur
peroxisome
oxidation of very long or branched fatty acids generates … and … which are high energy electron carriers, however these are …. in the peroxisome using molecule oygen forming h202 which is inactivated by catalse
NADH
FADH2
reoxidized
peroxisomal oxidation of branched or very long fatty acids occurs until the linear chain is … carbons long. After this the acyl-Coa molecule is transferred to the … very it is further oxidized to completion
18
mitchondrial matrix
disorder relating to impaired peroxisomal fatty acid oxidation can occur due to ? (3)
peroxisomal biosynthesis
deficiency of peroxisomal fatty acid oxidative enzymes
peroxisomal FA transport
disorders of peroxisomal fatty acid oxidation lead to accumulation of … and … fatty acids ?
this can lead to CNS manifestation including … which is degeneration of the white matter of the brain
long chain
branched chain
leukodystrophy
what are the 3 peroxisomal fatty acid oxidation disorders related to impairment of peroxisomal biosynthesis ?
what gene is commonly mutated in all 3 ?
Zellwegers syndrome
infantile refsum disorder
neonatal adrenoleukodystrophy
Peroxin (PEX)
what is the one disorder of peroxisomal fatty oxidation that is due to a mutation in an fatty acid oxidative enzyme ?
what enzyme is mutated
adult refsum disease
phtenic acid oxidase
what is the one disoder of peroxisomal fatty acid oxidation that is due to mutation in gene that codes for a fatty acid transporter that brings them into the peroxisome ?
what functional FA transport is absent ?
X linked adrenoleukodystrophy
ABCD1
lorenzos oil was used to treat …
it can prevent … synthesis of long chain fatty acids
X linked adrenoleukodystrophy
endogenous
Regulation of fatty acid oxidation occurs at the level of which enzyme ?
which product of fatty acid synthesis regulates this enzyme and how?
how do insulin an glucagon reguate the production of malonyl CoA
carnitine acyl transferase 1
malonyl CoA- commited step of fatty acid synthesis
inhibits the activity of carnityl acyl transferase
insulin leads to dephosphorylation of ACC which leads to increased productin of malonyl - insulin signals that we do not need to use fatty acids for oxidation
glucagon leads to phosphorylation of ACC and reduces its activity - less malonyl CoA then more beta oxidation
some acetyl CoA produced by beta oxidation may be converted to … bodies.
Name 2 of these molecules
ketone
acetoacetate
beta hydroxy buytrate
ketone bodies are made by the … and can be used as an alternative energy source by the …? In these tissues it can be converted to … and oxidized by the TCA cycle
liver
brain, heart and muscle
acetyl CoA
In prolonged fasting … will be oxidized to … and some of the … will be converted to … and released into circulation which can be used as an energy substrate numerous other tissus
fatty acids
acetyl CoA
ketone bodies
ketone bodies are a major source of energy for the … during starvation ?
brain
one of the key characteristics of ketone bodies is that they are water … therefore do not require … in the blood during transport
soluble
serum binding protein
ketone bodies are a salvage system to utilize excess … generated in the liver
acetyl CoA
In type 1 diabetes … defiency causes liver to switch metabolism to … and .. ./… catabolism
gluconeogenesis
fat and protein
prolonged gluconeogenesis in T1DM depletes … which is an intermediate of the TCA cycle and excess fatty acid oxidation leads to a surplus of …
Excess … is shunted towards …. formation
oxaloacetate
acetyl CoA
acetyl CoA
ketone body
excessive concentratin of ketone bodies in the blood will … the pH and increase the … of blood. The consequences of this are (2)?
lower
increase
acidosis (ketoacidosis)
dehydration - movement of fluid from the interstitium to circulation
cholesterol synthesis mainly occurs in the ?? (3)
liver
intestine
steroidogenic tissues (adrenal gland, gonads)
Carbon atoms of cholesterol are derived from the … group of ….
… must be transported out of the mitochindrial matrix, which achieved by the … which is also used for fatty acid synthesis
acetyl
acetyl CoA
acetly CoA
citrate shuttle
cholesterol synthesis starts in the … and is finished in the … of the cell
cytosol
endoplasmic reticuulum
cholesterol synthesis requires … as a cofactor, which offers … power for the pathway
NADPH- involved in numerous biosynthetic pathways
reducing
step 1 of cholesterol synthesis involves the conversion of … acetyl CoA molecules to form …
… is then reduced to from … and this reaction is catalyzed by …
3
HMG CoA
HMG CoA
mevalonate
HMG CoA reductase
conversion of … to … by … is the rate limiting step in cholesterol synthesis
HGM CoA
mevalonate
HMG CoA reductase
3 mechanisms to regulate HMG CoA reductase
- Phosphoryaltion by …. which … the enzyme
- enzyme … is regulated by cholesterol levels. High cholsterol than decreased….
- increased cholesterol can also regulate the levels of HMG CoA reductase at the level of …. mediated by
AMP-activated protein kinase
half life
transcription
sterol regulatory element binding protein (SREBP)
how does cholesterol regulate the transcription of HMG CoA reductase gene?
cholsterol will complex with sterol regulatory element binding protein (SREBP) and translocate to the nucleus and act as a transcription factor - decreasing the transcription of HMG CoA reductase
what enzyme do statins target. mechanism of action and what is the outcome?
target HMG CoA
compeitive inhibition of enzyme - transition state analoug (tetrahedral intermediate)
impair endogenous cholesterol synthesis
step 2 of cholesterol synthesis involves the conversion of (6C) … to 5(C)….
mevalonate
isopentenyl pyrophospahte
cholesterol is built up by the condensation of …. which are … carbon units in a head to tail arrangement
isopentenyl pyrophosphate (IPP)
5
condensation of IPP with another IPP forms …. and this is … carbons
geranyl pyrophosphate
10
condensation of geranyl pyrophosphate which is … carbons with …. forms …. which is … carbons
10
IPP
farnesyl pyrophosphate
15
during step 3 of cholesterol synthesis, ultimately we get the condensation of two 15 carbon … resulting in
farnesyl pyrophosphate
squalene
is an important biologic molecule as it is a precursor to many different biological molecules (e.g fat soluble vitamins, quinone electron carriers)
isopententyl pyrophosphate (IPP)
in the last step (4) of cholesterol synthesis we get the conversion of …. to …. through a number of … reactions. … is then further modified resulting in cholesterol
squalene
lanasterol
cyclization
lanosterol
what are the 3 main roles of cholesterol ?
used for steroid hormone synthesis
integral part of cell membrane - regulates its fluidity
can be transformed into bile acid/salts which aid in the digestion of lipids
in regards to cholesterol homeostasis of hepatocytes what are mechanisms that cholesterol enters ? (4)
- chylomicron remnants (exogenous dietary cholesterol)
- VLDL remnants
- LDL uptake
- HDL uptake
in regards to cholesterol homeostasis how does cholesterol exit hepatocytes ?
- distribition to extrahepatic tissue by VLDL
- bile acid/salt synthesis
what effect does oversupply of cholesterol in hepatocytes have on LDL receptor expression ?
decreases expression resulting in decreased uptake of LDL from circulaiton
what are 3 mechanisms by which hepatocytes can decrease intracellular cholesterol levels?
- decrease HMG CoA reductase - rate limiting step of cholesterol synthesis
- decrease LDL uptake by modifying the expression of LDL receptor at the plasma membrane
- bile salt synthesis - however this is controlled by external stimulus
liver stores cholesterol often in the form of ??
what is the only mechanism for cholesterol elimintation from the body?
why is this mechanism not efficient in cholesterol elimination?
bile acid/salt synthesis
most of the bile salts are reabsorbed in the ileum of the small intestine
deoxycholic acid is a common?
glycocholic acid and taurocholic acid are common?
bile acid
bile salts
prostaglandins, thromboxanes, and leukotrienes are derived from …
these molecules are generally classified as …
arachadonic acid
pro-inflammatory
derivatives of …. acid are classified as … but unlike derivatives of arachadonic are cardio protective, anti-inflammatory, and anti-carcinogenic
eicosanoids
eicosapentaenoic acid
arachadonic acid is incorporated into…. at C2 of glycerol.
glycerophospholipids
arachadonic acid is released from glycerophospholipds by the action of …
phospholipase A2
prostaglandins are formed by the … and … of arachadonic acid by the action of … in the endoplasmic reticuulum resulting in
oxidation
cyclization
cyclooxygenase 1 and 2
PGH2
thrombaxane is synthesized from … by ….
PGH2
thromboxane synthase
leukotrienes are synthesized from … by a family of …. enzymes
arachadonic acid
lipooxygenase (LOX)
Apirin (NSAID) is a … inhibitor
mechanisms of inhibition
COX-1 and 2
irreversibly acetylates serine in the active site of the enzyme
aspirin blocks the formation of prostaglandins but also … which decreases the risk of blood clotting
thromboxane - thromboxane formed from PGH2 which is generated through the action of cyclooxygenases
Vioxx was a selective …. inhibitor but was withdrawn from the market due it leading to a increases incidence of … events
COX-2
cardiovascular
If glycerophospholipids contains an unsaturated fatty acid (arachadonic acid) it will be attached to carbon … of glycerol
2
synthesis of phosphatidate involves the attachment of 2 activated …. to ….
fatty acids
glycerol-3-phosphate can be derived from … of glycerol. this only occurs in the …
glyercol-3-phosphate can also be derived from the reduction of … which is an intermediate of …
phosphorylation
DHAP (dihydroxyacetone-3-Phosphate)
glycolysis
1,2 diacylglycerolphoshate is also referred to as… and is the basic unit for glycerophospholipids
phsophatidate can also we used for the synthesis of … by removing the phosphate and esterifying a third…
phosphitidate
triacylglycerols
fatty acid
… are key enzymes in the degradation of glycerophospholipids. Reaction products include … (3). These may have some novel function or be metabolized or recycled
mono/diacylglycerols
glycerol
free fatty acid
… is key membrane glycerophospholipid involved in cell signalling ?
phosphatidyl inositol
activated phospholipase cleaves … into … and …
… binds to receptor on the endoplasmic reticuulum leading to increased cytosolic levels.
… activates ….
PIP2 (phosphatidyl inositol-4,5-bisphosphate)
DAG (diacylglycerol)
Inositol-1,4,5-trisphosphate (IP3)
IP3
DAG
protein kinase C
what is the parent compound of sphingolipids ?
ceramide
… is a sphingolipid metabolite that is a mediator in many cellular events including apoptosis, proliferation, necrosis, inflammation, senescence, differentiation
ceramide
sphingosine-1-phosphate is a sphingolipid …..
metabolite
ceramide synthesis
step 1 add … and …
step 2 attach fatty acyl coA
palmitoyl CoA
glycosphingolipid breakdown occurs in the … . this is an organelle in the cell
lysosome
glycosphingolipid breakdown is most active in … tissue where they are abundant
neural
…. are hydrolyzed to ceramide in … by the action of glucosidase, galactosidases, neuraminidases, hexosaminidases, sulfatases
glycosphingolipids
lysosome
…. lead to growth of lysosome and eventually cellular apoptosis
(sphingo) lipid storage disease
sphingolipidoses
lysosomal storgage disease
… is a disease due to defiency of beta hexosaminidase A.
Tay Sachs disease
…. enzyme usually cleaves N-acetyl-galactosamine (GalNac) from glycosphingolipids and dysfunction is present in … disease
beta hexosaminidase A
Tay Sachs
what are the 3 clinical subtypes of Tay Sachs disease? list from most severe to lease
infantile
juvenile
Adult
Tay Sachs disease leads to an accumulation of …
GM2 gangliosides
what is the main symptom of Tay Sachs disease?
progresive neurological impairment
… is a disease due to deficiency of beta glucosidase leading to the accumulation of glucosylceramide
Gauchers disease
Gauchers disease is caused by the defiency of … which leads to glucocerebroside accumulation
Beta glucosidase
cells that have accumulation of glucosylcerebrosides are referred to …. cells
Gaucher
Gauchers disease effects the …. system - cells descending from monocytes.
reticuloendothelial cells
Gauchers disease can present with infiltration of…. , …megaly and skeletal and CNS complications
bone marrow
heaptosplenomegaly
…. subtype of gauchers disease account for the vast majority of cases
type 1 - adult, non neuropathic
type 2 and 3 gauchers disease are referred to as … and …, respectively.
infantile - acute neuropathic
juvenile
Gauchers disease can be successfuly treated using ….
enzyme replacement therapy
what are the two 3 carbon sugars
glyceraldehyde-3-phosphate
dihydroxyacetone
function of monosaccharides?
fuel
cell-cell communication
structural
sugars can be classified as … or … depending on the location of the carbonyl group
aldoses
ketoses
nearly all monosaccharides found in the body are in the …. configuration
the -OH group on the penultimate carbon (last chiral carbon) is pointing to … on a fischer projection
D
right
D and L glucose are … of eachother
enantiomers - mirror images
steroisomers are molecules with the same structure and chemical formula but have different … at one or more … carbons
chirality
chiral
what are the three most common aldohexoses found in the humman body?
these are all … of eachother
D glucose
D mannose
D galactose
diastereomers
formation of the cyclic structure of carbohydrates involves -OH of the … carbon and carbon 1
penultimate
monosaccharide that has a 5 member ring in cyclic form is a ….
6 member ring …
furanose
pyranose
… is the carbon containing the carbonyl group of a monosaccharide
anomeric carbon
cyclic forms of D glucose can exist in … and … confirmations
alpha (-OH of anomeric carbon below the page) and beta (-OH of anomeric carbon above the plane of the page)
… bonds form between the anomeric carbon of a monosaccharide and an hydroxyl/amine group of another
glycosidic bond - can exist in alpha and beta conformation
glycosidic bonds can be … linked or … linked
O
N
what are three common dissacharides ?
maltose
lactose
sucrose
maltose is made of ??
glucose-alpha (1,4) - glucose
sucrose is made of ?
glucose - alpha (1,2) - fructose
lactose is made of ?
galactose - beta (1,4) - glucose
why do humans store glucose as a polysaccharide ?
reduce the osmotic pressure of stored glucose - if glucose was just free in the cytoplasm in high concentration this would cause the cell to swell and burst
…. is the form that carbohydrates are stored in humans while plants use …. and …
glycogen
amylose
amylopectin
amylose only contains …. bonds between glucose molecules therefore it is not ….
alpha 1-4 bonds
branched
amylopectin contains both … and … bonds. … bonds allow amylopectin to be branched
alpha 1-4
alpha 1-6
alpha 1-6
amylopectin and glycognen both contain … and … bonds, however glycogen is more highly …
alpha 1-4
alpha 1-6
branched
cellulose is a homopolymer of ….
bonds between …. molecules are… which inhibits it from being broken down in the GI tract of humans. why?
glucose
beta 1-4 glycosidic linkages
we do posses the enzyme to break beta 1-4 glucose bonds
beta 1-4 linkage between glucose molecules in cellulose allows it adopt a …. conformation which allows it to be a good structural molecule
linear
starch, unlike cellulose is … in water and is a source of ….
soluble
energy
…. is formed by the addition of an amino group to glucose. it is the precursor for the formation of glycoproteins and glycolipids. it also is found in the … fluid around joints
glucosamine
synonvial
galactosamine is a constituent of …. hormones such as … and …
glycoprotein
FSH
LH
glucose can be oxidized at carbon 6 resulting in a ….. functional group. this molecule is now referred to as glucuronic acid
carboxylic functional group
gluronic acid is involved in the … of bile acids
solubilizatioin
glucose measurment by devices has … enzyme present on the strip and therefore measures…
glucose oxidase
oxidated glucose
… is a sugar found in ATP
glucose to … is catalyzed by aldose reductase. This enzyme reduces the … group of glucose to an -OH
sorbitol
aldehyde
galactose can be reduced at the anomeric carbon to form …..
…. catalyzes this reaction
galactilol
aldose reductase
…. converts glucose to sorbitol
… converts sorbitol to fructose
aldose reductase
sorbitol dehydrogenase
in cases of …. we get increased flux thorugh …. pathway resulting in increased … which may lead to cataracts.
hyperglycemia
polyol pathway
sorbitol
increased levels of … can be toxic to a cell and lead to cataracts of the lens
sorbitol
… pathway is used to convert glucose to fructose in seminal vesicles.
… is an intermediate of the pathway
polyol
sorbitol
polyol pathway is implicated in … complications due to diabetes. this is due to excess …
microvascular
sorbitol
aldehyde groups of sugars non-enzymatically form … with amino groups of proteins
schiff bases
what is measured to determine glycemic control in diabetic patients. This is more effective than individual glucose readings
glycosylated hemoglobin (HbA1c)
… are made up of repeating dissacharide units. each disaccharide unit made of a … sugar and a … sugar
glycosaminoglycans
uronic sugar
amino sugar
… are long linear chains of glycosaminoglycans attached to a core protein
proteoglycans
proteoglycans are a key component of …. due to its abilitty to absorb …
they can be found in .. fluid of joints, vitrous humor of eye, and cartilage
connective tissue (ECM)
water
proteoglycans are synthesized in the …. and then secreted into the ….
degradation of proteoglycans involves … (intracellular organelle)
endoplasmic reticuulum
ECM
lysosome
Glycoproteins
O linked - branches grow by sequential addition of monosaccharide units to …/… amino acids in associated protein
N-linked - branches grow by sequential addition of monosaccharide units to …. residue found in protein
serine
threonine
Asparagine
…. are the activated form of monosaccharides which are involved in the synthesis of GAGs and glycoproteins
UDP-sugars
… is a disease that is caused by impaired localization of lysosomal enzymes to the lysosome from the ER
I cell disease
in I cell disease a mutation is found in …. enzyme which impairs addition of …. to enzymes which is used to target proteins to the lysosome.
phosphotransferase
mannose-6-phosphate
pathophysiology of I cell disease
typical prognosis
lysosomes become engorged in non-digested material (seen under microscope as inclusion bodies)- this can lead to cellular apoptosis
death within first 10 years of life
digestion of carbohydrates starts in the …. through the action of …
this enzyme break … bonds forming …
oral cavity
salivary amylase
glucose-alpha (1,4) - glucose
dextrins
… is secreted from the liver and acts on starches to cleave …. bonds and like salivary amylase form ….
pancreatic amylase
glucose- alpha (1,4) - glucose
dextrins
how do maltose and isomaltose differ
maltose: glucose -alpha (1,4) - glucose
isomaltose - alpha (1,6) - glucose
…. is a brush border enzyme that cleaves non-reducing ends of oligosaccharides and alpha1,4 bonds of maltose to produce … monomers
maltase
glucose
… is a brush border enzyme that cleaves alpha 1,6 bonds of branched oligosaccharides
isomaltose
sucrase is a …. enzyme that converts … to …. and ….
brush border
sucrose
glucose
fructose
…. is a brush border enzyme that converts …. to galactose and glucose
lactase
lactose
what is euglycemia ?
normal level of blood glucose (fasting <5.6 mMol)
what are the 3 key hormones involved in increasing blood glucose levels?
glucagon
cortisol
epinephrine
what is the one hormone that decreases blood glucose levels?
insulin
failure to maintain blood glucose levels above 3-3.5 mmol/L results in ….
neuroglycopaenia
Insulin leads translocation of the …. glucose transporter to the cell membrane in … and … tissues
Glut 4
muscle
adipose
True or False? Insulin acts on the hepatocytes of the liver and lead to increased translocatino of the Glut4 glucose transporter to the cell membrane ?
False - hepatocytes do not express Glut 4. they instead constitutvely express GLUt 2 transporter
Insulin acts on the liver to stimulate …. and inhibit ….
glycogenesis
gluconeogenesis
Insulin is produced in the … cells of the endocrine pancreas in response to …
beta
increased blood glucose after intake of a meal
Insulin acts on adipocytes to increase …. translocation to the cell membrane and it also inhibits …. resulting in less breakdown of triglycerides
Glut 4
lipolysis
…. acts on muscle cells to increase … tranlocation to the cell membrane for uptake of glucose and … also stimulares storage of glucose by promoting …
insulin
GLUT24
Insulin
glycogenesis
glucagon is produced and secreted from … cells of the endocrine panceras.
glucagon stimulates breakdown of …. and release of … from adipocytes
glucagon stimulates …. and … in the liver and inhibits …
alpha
triacyl glycerols
fatty acids
glycogenolysis
gluconeogenesis
the brain uses … as its primary fuel, however during starvation it can use …
the brain cannot utilize … for fuel as they are too … to cross the blood brain barrier
glucose
ketone bodies
fatty acids
hydrophobic
RBCs soleyl rely on ..,. for fuel
RBCs have no … so they cannot do beta oxidation and or TCA cycle
glucose
mitcochondria
liver generates but does not utilize … for energy
ketone bodies
…. can only utilize glucose/anerobic glycolsys becasue they do not posses a …
Red blood cells
mitcochondria
…. cells can store glucose as glycogen but cannot release glucose into circulation when blood glucose levels are low
muscle
adipose tissue can take up … and … where they are converted to … and stored
glucose
fatty acids
triacylglycerols
during fasting the … primarily generates energy via fatty acid oxidation
liver
during fasting glycerol from fatty acid breakdown in the adipose tisue can be sent to the … and be phosphorylated and utilized in …
liver
gluconeogenesis
… can switch from using glucose to … during prolonged fasting in order to spare … from occuring
brain
ketone bodies
muscle wasting
…. is the only fuel that can be used by all cells of the body
glucose
glucose is taken up by the brain and …. via …. trasporter. this transporter is …. independent
red blood cells
insulin
… transpoter is present on hepatocytes and … cells of the pnacreas
Glut2
beta cells
glucose taken up by glut2 transporter of pancreatic beta cells lead to the secretion of … into circulation
insulin
during aerobic respiration/glycolysis … is reduced completely to … and …
this occurs in cells that posses a … and have sufficient … available
pyruvate
mitochondria
O2
during anaerobic respiration … is reduced to … which allows for the regeneration of ….
pyruvate
lactate
NAD+
glycolysis takes place in the …. of the cell
cytoplasm
in the first step of glycolysis glucose is…. by the …. enzyme in the liver and …. enzyme in extrahepatic tissue. the product of this step is …
phosphorylated
glucokinase
hexokinase
glucose-6-phosphate
… is the enzyme in the liver and … is the enzyme in the rest of the tissues that phoshorylates glucose to form glucose-6-phosphate
glucokinase
hexokinase
…. enzyme experiences auto-feedback inhibition by its own product glucose-6-phosphate, while …. DOES NOT experience auto-feedback inhibition by its own product glucose-6-phosphate
hexokinase
glucokinase
glucokinase is found not only in the liver but also in the … cells of the …
beta
pancreas
the step of glycolysis catalyzed by …. represents the first committed step of glycolysis
phosphofructokinase (PFK)
Phosphofructokinase catalyzes the rxn ….
this reaction requires…
fructose-6-phosphate to fructose-1,6-phosphate
ATP
in non-hepatic tissue PFK is inhibited by ….
PFK is … regulated in the liver, namely by … and …
high ATP/ADP ration
hormonally
insulin
glucagon
in hepatocytes insulin activates …. leads to the … of PFK2 which … it. this leads to increased production of … which … regulates PFK1 activity
phosphatases
dephosphorylation
activates
fructose-2,6-bisphosphate
positively
in hepatocytes … will lead to the activation of PKA. this will … PFK2. phosphorylated PFK2 functions as a …. and will …. frutose-2,6-bisphosphate therefore reducing the activity of … in order to promote ….
glucagon
phosphorylate
phosphatase
dephosphorylate
PFK1
gluconeogenesis
during the last step of glycolysis … and … are generated. the substrates for this reaction are … and …
this reaction is catalyzed by …
phosphoenol-pyruvate
ADP
pyruvate
ATP
pyruvate kinase
… is an autosomal recessive disorder that is the most common cause of hemolytic anemia. the gene that is affected is …..
symptoms of this include … due to the excessive degradation of RBCs and … which is due to increased bilirubin
pyruvate kinase deficiency
PKLR
splenomegaly
jaundice
why is pyruvate kinase deficiency so detrimental for red blood cells?
only generate ATP from glycolysis. Do not posses mitochondria to do betaoxidation and retrieve ernegy from acetyl COA
what are the 4 fates of pyruvate ?
converted to alanine
converted to acetyl CoA which is can enter TCA cycle or be used for fatty acid synthesis
converted to lactate during anaerobic respiration-lack of cellular oxygen availability
converted to oxaloacetate for gluconeogenesis
during anaerobic respiration … is reduced to … by the enzyme …
pyruvate
lactate
lactate dehydrogenase
conversion of pyruvate to lactate is crucial during anaerobic respiration as it allows regeneration of … which allows glycolysis to continue to occur
NAD+
reduced during glycolysis to NADH
lactate generated by anaerobic respiration can enter the blood stream and be taken up by the … and there it can be used as a substrate for ….
liver
gluconeogenesis
levels of lactate in the blood above 4-5mmol/L can can ….
lactic acidosis
… can result from hyoxia/poor tissue perfusion or excessice alcohol consumption. Both of these are associated with less oxidative phosphorylation
lactic acidosis
reduced activity of the electron transport chain (ETC) while glycolysis is still occuring can result in increased …. this stimulates the conversion of pyruvate to … in order to refrom …
NADH
lactate
NAD+
alcohol degradation leads to increased … which drives … production in order to regernate cellular ….
this is why excess alcohol consumption can lead to ….
NADH
lactate
NAD+
lactic acidosis
…enzyme receives autofeedback from its product glucose-6-phosphate in the first step of glycolysis. this is not the case with the ‘equivlanet’ enzyme which is found predominantly in the liver and in the pancreas
hexokinase
pyruvate kinase is active in its … form which is promoted by … (hormone)
dephosphorylated
alanine inhibits …. enzyme that is involved in glycolysis
pyruvate kinase
fructose-1,6-phopshate is a positive allosteric modulator of … enzyme that is involved in glycolysis
pyruvate kinase
… leads to the phosphorylation of pyruvate kinase which … its activity and promotes … instead of glycolysis
glucagon
gluconeogenesis
in the liver PFK1 is under … control while in non hepatic tissue PFK1 is controlled by … and …
…. is a substrate and inhibtor of PFK1
… activates PFK1
hormonal
ATP
AMP
ATP
AMP
gluconeogenesis occurs in the … and to a lesser extent …. after approximately 8 hours of fasting
liver
kidneys
what are 3 precursor molecules for gluconeogenesis ?
lactate, amino acids (e.g alanine), glycerol
…. is not a substrate for gluconeogenesis, however oxidation of this molecule generates energy required for this process
acetyl CoA
these 3 enzymes that are required for glycolysis are inactive during gluconeogenesis in order to avoid futile cycling between the two pathways
glucokinase
PFK1
pyruvate kinase
during gluconeogenesis …. enzyme is inhibited so pyruvate is not converted to acetyl CoA
pyruvate dehydrogenase
synthesis of 1 mole of glucose from 2 moles of pyruvate requires … moles of ATP
6
the cori cycle is also referred to as the … cycle
…. released from muscle cells after glycolysis is reconverted back to … by the liver
… produced by the liver using … as a substrate is taken up by the muscle cells
lactic acid
lactate
glucose
glucose
lactic acid
… and … are the main muscle derived amino acids used for gluconeogenisis
alanine
glutamine
alanine can be converted to pyruvate by the action of what enzyme ?
alanine aminotransferase (ALT)
the … is the only organ capable of utilizing glycerol from the breakdown of triacylglycerols
liver
the … is the only organ capable of utilizing glycerol because it posseses the enzyme …
. this product can be used for … and … and can be used as an intermediate in …
liver
glycerol kinase
gluconeogenesis
triglyceride synthesis
glycolysis
in the first step of gluconeogenesis pyruvate is converted to ….
this reaction utilizes the enzyme … which is found in the … of the cell
… enzyme requires …. as a cofactor
oxaloacetate
pyruvate carboxylase
mitochondria
during gluconeogenesis … made from pyruvate cannot pass through the mitochondrial membrane from the mitochondrial matrix to the cytosol so it must be temorarily converted to …./….
malate/asparate
in the second step of gluconeogenesis oxaloacetate is converted to ….
this reaction is catalyzed by the enzyme … which removes a … and adds a … to oxaloacetate
this steps requires energy input from ….
phosphoenolpyruvate
phosphoenolpyruvate carboxykinase
CO2
phosphate
GTP
during gluconeogenesis fructose-1,6-bisphosphate is converted to …. which is catalyzed by …
fructose-6-phosphate
fructose-1,6-bisphosphate
fructose-1,6-bisphosphatase is positively allosterically regulated by ….
fructose-1,6-bisphosphatase is negatively allosterically regulated by … and …
…. positively allosterically regulates phosphofructokinase1 and negatively alosterically regulates fructose-1,6-bisphosphatase
ATP
AMP
fructose-2,6-bisphosphate
fructose-2,6-bisphosphate
… enzyme is a key enzyme of gluconeogenesis and glycogenolysis. It catalyzes the conversion of glucose-6-phosphate to glucose. This allows glucose to exit the hepatocytes and enter circulation
glucose-6-phosphatase
regulation of gluconeogenesis
during fasting …. (hormone) levels increase and this favours gluconeogenesis
… (hormone) activates… (kinase) which will phosphorylate a number of downstream targets
decreased … (hormone) during fasting results in the release of fatty acids from adipose tissue
glucagon
glucagon
protein kinase A
insulin
regulation of gluconeogenesis
pyruvate carboxylase which catalyzes the carboxylation reaction transforming pyruvate into … is positively allosterically regulated by …
transcription of the gene coding for phosphoenolpuruvate carboxykinase is positively regulated by …
pyruvate kinase is inhibited by phsphorylation by … which is activated in response to … (hormone)
glucokinase during gluconeogenesis is relatively inactive due to the relatively low … levels
oxaloacetate
Acetly-CoA
cAMP - binds CREBP
PKA
glucagon
glucose
… is a cofactor that is involved in numerous carboxylation reactions (catalyzed by family of carboxylase enzymes)
… is a … carrier on the surface of carboxylase enzymes
excessive ingestion of …. which is found in egg whites has been associated with biotin deficiency
biotin
biotin
CO2
avidin
… is the main storage of carbohydrate in animals. It is mainly stored in the … and … with a larger amount found in the …
glycogen
liver
muscle
muscle
glycogen in muscle provides energy to muscle but does not supply glucose for … during times of fasting. this is because muscle cells do not posses … enzyme
circulation
glucose-6-phosphatase
advantage of storing some energy as glycogen instead of all in triacylglycerol form is that energy cannot be yielded from fat in the same
additionally some cells only use … for energy
time
glucose
…. supplies the glucose moieties used during glycogen synthesis
new glucose molecules are attached at …. ends of the preexisting glycogen molecule
at the reducing end one glucose molecule is attached to the protein … which primes glycogen synthesis
UDP-glucose
non-reducing
glycogenin
glycogen synthesis
glucose is first converted to … by the enzyme … in the liver or … in the muscle
… is then coverted to … by …
glucose-1-phosphate is then converted to … by the action of … this molecule can suppply the glucose moiety for glycogen synthesis
glucose-6-phosphate
glucokinase
hexokinase
glucose-6-phosphate
glucose-1-phosphate
phosphoglucomutase
UDP-glucose
glucose-1-phosphate uridyl transferase
…. is an enzyme involved in converting glucose to glycogen. It acts as a primer, by polymerizing the first few glucose molecules, after which other enzymes take over. It is a homodimer of 37-kDa subunits and is classified as a glycosyltransferase.
glycogenin is attached to the … end of the first glucose molecule
the primers which are attached to glycogenin are partially degraded … molecules
glycogenin
reducing
glycogen
branches in glycogen are achievd through … bonds betwen glucose molecules
alpha 1-6
branches in glycogen increase … of glycogen
braches occur roughly every …-… residues
solubility
7-9
…. enzyme is responsible for creating branch in glycogen. this enzyme has two functions;
first it cleaves …. bonds
second it makes …. bonds
glucosyl 4:6 transferase (transferase typically break and form other bonds- move around groups)
glucose-alpha (1-4) bonds
glucose- alpha (1-6) bonds
…. refers to the process of the breaking down of glycogen into glucose monomers
glycogenolysis
… is the main enzyme for the responsible for sythesis of glycogen
this enzyme forms alpha 1-4 bonds between glucose molecules
glycogen synthase
… is the key enzyme involved in the degradation of glycogen
this enzyme utilizes …. to cleave … bonds between glucose molecules producing ….
glycogen phosphorylase
inorganic phosphate
alpha 1-4 bonds
glucose-1-phosphate
glycogen phosphorylase cleaves glucose molecules from glycogen until there is …. units remaining before the branch point
4
besides glycogen phosphorylase which other enzyme is required for glycogenolysis ?
debranching enzyme
what 2 functions does debranching have ?
4:4 transferase activity - transfers 3 of the remaining 4 glucose molecules to another chain
alpha 1-6 glucosidase acitvity - cleaves of remaining bond that originally was created to form a branch
…. is the enzyme used in gluconeogenesis and glycogenolysis to release free glucose into circulation
genetic defiency of this functional enzyme leads to … disease in which patients show severe ….
glucose-6-phosphatase
von Gierke’s disease
hypoglycemia
hormonal regulation of glycogen synthesis and breakdown
… acts to … glycogen synthase thereby activating it
… also acts to …. glycogen phosphorylase thereby …. it
insulin
dephosphorylate
insulin
dephosphorylate
inactivating
hormonal regulation of glycogen breakdown/synthesis
glucagon leads to an intracellular increase in … by activating adenyl cyclase
… then goes into activate PKA
PKA will … glycogen synthase thereby ….
PKA will … glycogen phosphorylase thereby …
cAMP
cAMP
phosphorylate
inactivating
phosphorylate
activating
fates of muscle glycogen
muscle does not contain …
glucose-1-phosphate produced by .. provides energy via glycolysis for contraction
glucose-1-phosphate is converted to glucose-6-phosphate by the enzyme …
glucose-6-phosphatase
glycogenolysis
phosphoglucomutase
…. is classified as a type … glycogen storage disease
it is caused by a mutation in … enzyme
the main consequence of this is inability to release …. into circulation during fasting
biochemical testing may reveal decrease blood …, which is also reffered to as … and elevated blood ….
the second finding is due to impaired … as this enzyme is also involved in this pathway
the patient may present with an enlarged … which is clincally referred to as …
von Gierkes disease
1
glucose-6-phosphatase
glucose
glucose
hypoglycemia
lactate
gluconeogenesis
liver
hepatomegaly
Coris disease is a …. disease and is classfied as type ….
it results from a mutation in the …. enzyme which is required for glycogen breakdown
this enzyme normally has 2 functions which are …. and ….
it is indistinguishable clincally from type … glycogen storage disorder
3
debranching enzyme
4:4 transferase activity
alpha 1-6 glucosidase activity
1 (von gierkes disease )
… is a glycogen storage disorder that only affects muscle cells
it is classified as type …
functional form of muscle …. enzyme is absent
clincally patient present with exercise ….
it is the … severe form of glycogen storage storage disease
patient do not experience …. unlike von gierkes and corris disease
McArdles disease
4
glycogen phgosphorylase
intolerance
least
hypoglycemia
glycogen storage disease
von gierkes is classfied as type …. and is due to a mutation in … enzyme
Cori’s disease is classified as type … and is due to a mutation in … enzyme
McArdles is classified as type …. and due to a mutation in …. enzyme
in which of these disease is the patient most likely to present with lactic acidosis and why?
1
glucose-6-phosphatase
3
glycogen debranching enzyme
4
muscle glycogen phosphorylase
von gierkes disease - glucose-6-phosphatase is involved in gluconeogenesis as well. if this is impaired pyruvate may be transformed into lactate
…. is a unique glycogen storage disease
it is classified as type ….
is results from dusfucntional …. enzyme which is found in the …. (organelle of the cell).
this disease results in glycogen accumulation in the …. which in turn can lead to cell death
this disease not lead to …. of the blood as lysosomal glycogen breakdown is not required for maintaining blood glucose levels.
pompe disease
2
acid alpha-glucosidase (acid maltase)
lysosome
hypoglycemia
the classical form of pompe disease is …. onset.
in this form patients present with … , …. , and …..
infantile
hepatomegaly
myopathy
hypotonia
heart defects
Corri disease is a mutation in the … enzyme and is classified a type … glycogen storage disease.
it is characterized by the storage of structurally abnormal glycogen which is termed …..
debranching enzyme
type 3
limit dextrin
… is the first sign of corris disease in children
…./…. are elevated in the blood of these patients as metabolism switches other fuel sources besides carbohydrates
poor muscle tone
fatty acid/ketone
fructose to uses the …. transporter to enter enterocytes from the lumin of the small intestine.
GLUT5
fructose is taken up by hepatocytes of the liver by the …. transporter
GlUT2
Absorption of fructose by beta cells of the pancreas does not induce an …. response
in tissues other than the liver fructose is acted on by the enzyme …. to become …
this is an intermediate of glycolysis
however the liver vesion of this enzyme which is called… does not recognize fructose
hexokinase
fructose-6-phosphate
glucokinase
frutose metabolism in the liver
fructose is first converted to …. by the enzyme …. This is different to extra hepatic tissue where fructose is first acted on by … and converted to ….
fructose-1-phosphate
fructokinase
hexokinase
fructose-6-phosphate
in the liver fructose is first converted to … by the enzyme ….
after this …. is converted to … and … by the enzyme …
…. can then be phosphorylated by triose kinase to become
fructokinase
fructose-1-phosphate
aldolase B
dihroxyacetone-phosphate
glyceraldehdye
glyceraldehyde-3-phosphate
metabolism of fructose is quicker than that of glucose because the metabolism of fructose bypasses which rate limiting step of glucose metabolism in the liver?
phosphofructokinase1
fructose-6- phosphate to fructose-1,6-bisphosphate
fructose is higly … when ingested with glucose because glucose stimulates … (hormone) release which inhibits gluconeogenesis and therefore fructose metabolites (G-3-P and DHP) are converted to pyruvate and acetyl CoA
lipogenic
insulin
hereditary disorder of fructose metabolism usually appear …. months after birth when the baby stops ….
6 months
breast feeding
fructose-1-phosphate which is made by the enzyme … is a competitive inhibitor of what enzyme ? What is the role of this enzyme
therefore accumulation of fructose-1-phosphate in hepatocytes can have what effect on blood glucose levels ?
fructokinase
glycogen phosphorylase
main enzyme responsible for glycogenolysis
hypoglycemia
deficiency of this enzyme leads to elevation of blood and urine fructose but has no effect on blood glucose levels
fructokinase
….. deficiency is …. and is often diagnosed accidentally when a non-glucose reducing substance is detected in the urine of a patient
fructokinase
assymptomatic
deficiency of this enzyme results in a severe disorder of fructose metabolsim ?
aldolase B
aldolase B deficiency leads to the acumulatin of what in liver hepatocytes ?
this product is a competitive inhibitor of what enzyme that is required for glycogenolysis ?
fructose-1-phosphate
glycogen phosphorylase
infants with aldolase B deficiency are healthy until ??
they start to ingest fructose - this typically occurs after infants stop breastfeeding
aldolase B deficiency not only impairs the metabolism of fructose-1-phosphate but also impairs the metabolism of … whic impairs gluconeogenesis and glycolysis
fructose-1,6-bisphosphate
accumulation of fructose-1-phosphate in the cell leads to depletion of inorganic … and … which leads to increased urate prodution
phosphate
ATP
accumulation of fructose-1-phosphate inhibits this …. enzyme via competitive inhibition but also by consuming inorganic … which this enzyme requires
glycogen phosphorylase
phosphate
fructose -1 phosphate impairs gluconeogensis by inhibiting ….
glucose-6 phosphate isomerase
along with hypoglycemia aldolase B deficiency can lead to … which is due to the fact that it inhibits gluconeogenesis
lactic acidosis
what is a therapy for Pompe disease that has been approved?
enzyme replacement therapy - acid alpha glucosidase (acid maltase)
patients who have aldolase B deficiency are advised to have a diet free of … and … which allows them to remain symptom free
fructose and sucrose
galactose metabolism
when galactose first enters a cell it is …. by the action of ….
the resulting product is ….
phosphorylated
galactokinase (ubiquitous expression, not just liver)
galactose-1-phosphate
galactose-1-phosphate reacts with … which is catalyzed by the enzyme … to form glucose-1-phosphate and ….
UDP-glucose can be regernated from UDP galactose by the enzyme….
UDP-glucose
galactose-1-phosphate uridyl transferase
UDP-galactose
epimerase
glucose-1-phosphate generated from metabolism of galactose can be utilized for …. (catabolic process in muscle and liver) or transformed to … and be used for glycolysis
glycogenesis
glucose-6-phosphate
classical galactosemia results from deficiency of …
this leads to the accumulation of … in the cell
clinical features of this illness include vomitting, lethary, and failure to thrive soon after breastfeeding begins. Why does this cause failure to thrive soon after breast feeding begins?
galactose-1-phosphate uridyl transferase
galactose-1-phosphate
lactose is a major component of breast milk. it is broke down to galactose and glucose
…. galactosemia which leads to the accumulation of … in the cell is the more severe form as it impairs … synthesis and degradation
classical
galactose-1-phosphate
glycogen
non-classical galactosemia results from the deficiency of …. enzyme
galactokinase
….. leads to the accumlation of galactose which is reduced to …. by the enzyme … (also converts glucose to ….) and can lead to … of the lens of the eye
non-classical
galactinol
aldose reductase
sorbitol
cataracts
…. is the main pathway for generation of ….. and ribulose-5-phosphate
pentose phosphate pathway
NADPH
the Pentose phosphate pathway occurs in the … of the cell and branches from glycolysis at the level of ….
cytoplasm
glucose-6-phosphate
…. produced from the …. pathway of the pentose phsphate pathway is an important reductive reagent required for fatty acid synthesis as well as glutathione reduction
NADPH
oxidative
reduction of glutathione by NADPH protects against ….. damage
oxidative
….. which is a product of the pentose phosphate pathway is used for the synthesis of nucleotides but can also be converted back to glycolysis intermediates …. and ….. for the generation of pyruvate
ribulose-5-phosphate
fructose-6-phosphate
glyceraldehyde-3-phosphate
the …. pathway of the pentose phosphate pathway is irreversible and generates …. and …..
this pathway occurs when …. levels are low in the cell
oxidative
NADPH
ribulose-5-phosphate
NADPH
…. is synthesized by two dehydrogenase complexes at the …. and … step of the oxidative pathway of the pentose phosphate pathway
NADPH
1st
3rd
….. enzyme is responsible for the decarboxylation of …. to yeild the 5 carbon sugar ribulose-5-phosphate during the oxidative pathway of the pentose phosphate pathway. This reaction produces the second …. of the pathway
6-phosphogluconate dehydrogenase
6-phosphogluconate
NADPH
…. is a reducing agent made from the pentose phosphate pathway
NADPH
…. is important for the reduction of … which is an important anti-oxidant
NADPH
gluathione
the … pathway of the pentose phosphate pathway is reversible.
it can be used for the generation of …. from ribulose-5-phosphate and vice versa
non-oxidative
glycolytic intermedites
when … levels in the cell are …. the cell can use the non-oxidative pathway of the pentose phosphate pathway to synthesis ribulose-5-phosphate from …. intermediates
NADPH
high
glycolytic
in non-dividing cell where requirments for nucleotides are low, the ribuolse-5-p is reconverted to …. intermediates
3 moles of ribuslose-5-phosphate converted to 2 moles of …. and 1 mole of …
in these reactions … are donors and … and … are receptors
glycolytic
fructose-6-phosphate
glyceraldehyde-3-phosphate
ketoses
aldoses
… enzyme catalyses the first step of the oxidative pathway of the pentose phosphate pathway. this produces … which is an important cellular reducing agent
glucose-6-phosphate dehydrogenase
NADPH
……. deficiency is a X linked chromosome disorder. Mainly affects … cells . …. observed, usually in response to a trigger (antimalarial drugs)
antimalarial drugs usually undergo a redox reaction in the cell producing a large quantity of reactive oxygen species
insufficient production of …. in affected person causes excessive oxidative damage and lysis to occur
this mutation is thought to provide natural protection against…
glucose-6-dehydrogenase deficiency
red blood cells
hemolytic anemia
NADPH
malaria
…. is the site of the TCA cycle
matrix of the mitochondria
… is not directly required for TCA cycle. … is required for the reoxidation of coenzymes that are … in the process of the TCA cycle
oxygen
oxygen
reduced
TCA cycle overview
sequence of reactions that oxidizes …. to … and reduces nucleotides … and … to …. and …..
acetyl CoA
CO2
NAD+
FAD
NADH
FADH2
…. is the common product of catabolism of fat, sugar and protein
acetyl CoA
the role of the TCA is for energy production and …
biosynthesis
why does NADH lead to more ATP production than FADH2 ?
NADH drops off electrons at complex 1 of the ETC. this complex directly pumps protons into the intermembrane space
FADH2 is dropped off at complex 2 of the ETC. this complex is not responsible for directly pumping electrons into the intermembrane space
what role does the TCA play in gluconeogenesis ?
allows of the generation of ATP which is crucial to provide the energy for gluconeogenesis
TCA cycle begins with …. and not …. as proteins and fat can contribute … to the cycle independent of ….
acetyl coa
pyruvate
acetyl coa
pyruvate
primary fate of acetyl coa is … in the TCA cycle but in the cytoplasm is used for the generation of …. and …..
oxidation
fatty acids
cholesterol
what are the 4 fates of pyruvate and what enzyme catalyzes each reaction ?
can be converted to lactate (lactate dehydrogenase)
can be converted to alanine (alanine aminotransferase)
pyruvate converted to oxalaoacetate (pyrvuate carboxylase)
can be converted to acetyl coa (pyruvate dehydrogenase)
what is the general role of the pyruvate dehydrogenase complex?
convert pyruvate to acetyl-CoA
in the first step of the pyruvate dehydrogenase complex pyruvate is …. by the …. containing enzyme ….
the end product of this reaction is ….
decarboxylated
thiamine pyrophosphate
pyruvate dehydroganse
acyl-TPP
in the second step of the pyruvate dehydrogensae complex the two carbon …. is transferred onto …. and also oxidized which is catalyzed by the enzyme …
the product of this reaction is ….
acyl-TPP
lipoamide
dihydrolipoamide acyl transferase
acyl-lipoate
in the last step of the pyruvate dehydrogenase complex the …. group of … is transferred to ….
….. is then oxidized by … enzyme forming which high energy electon carrier ?
… then passes its electrons to …. which can then go on to donate the electrons to the electron transport chain
acyl
acyl-lipoate
coenzyme A
lipoamide
dihyroxylipoyl dehydrogenase
FADH2
FADH2
NADH
Pyruvate dehydrogenase complex and vitamins required for synthesis of pyruvate to acetyl coa
name all the cofactors, which aspect of the pyruvate dehydrogenase complex they are required for and what b vitamin they are derived from ?
thiamine pyrophosphate - required for pyruvate dehydrogenase enzyme. Requires thiamine (vitamin B1
coenzyme A - accepts acyl group from acyl-lipoate. requies pantothenic acid which is vitamin B5
FAD- accepts electrons from lipoamide to oxidize it- requires riboflavin which is vitamin B2
NAD - accepts electrons from FADH2. requires nicotinamide which is vitamin B3
why are B vitamins referred to as energy supplements?
vitamin B1,2,3,5 are required for pyruvate dehydrogenase complex
what are 3 negative allosteric regulators of the pyruvate dehydrogenase complex?
NADH, acetyl coa and ATP
During energy excess, signalled by increased levels of … the entry of pyruvate into the TCA cycle is ….
ATP
prohibited
high levels of … and … produced by fatty acid oxidation prevents … from entering the TCA cycle
therefore pyruvate can be redirected towards ….. pathway during fasting when FA oxidation is elevated
NADH
Acetyl-CoA
pyruvate
gluconeogenesis
metabolism of alcohol leads to an increased level of ….
this is a … regulator of pyruvate dehydrogenase complex
therefore pyruvate may shifted towards production of ….. in order to regenerate cellular ….
in excess quantity alcohol consumption can therefore lead to ….
NADH
negative
lactate
NAD+
lactic acidosis
thiamine deficiency (vitamin …) decreases ….. and …. enzyme activity
decreased enzymatic acitivity especially of … leads to shunting of pyruvate to form … resulting in ….
thiamine deficiency is often obsergved in people who are … and have …. disease
B1
pyruvate dehyrogenase
alpha ketoglutarate dehydrogenase
pyruvate dehydrogenase
lactate
lactic acidosis
alcoholics
Beriberi
beriberi disease is characterized by …. deficiency
high-output congestive …. failure and …. symtpoms are strongly suggestive of beriberi disease
…. berberi - heart function effected and in some cases patients experience heart failure
….beriberi - damage nerves and can lead to a loss of muscle strength and paralysis
thiamine (B1)
heart
neurological
wet
dry
… abuse can impair absorption and storage of … leading to beriberi disease
alcohol ‘
thiamine
…. beriberi - caused by thiamine deficiency in the mother during pregnancy
infantile beriberi
in the first step of the TCA cycle …. and … react to form ….
this reaction is catalyzed by the enzyme …
…. is a product of this reaction and also a negative allosteric inhibitor this enzyme
acetyl coa
oxaloacetate
citrate
citrate synthase
citrate
citrate contains how many carbons?
6
in the TCA cycle citrate is converted to …..
isocitrate
in the TCA cycle isocitrate is acted on by the enzyme ….
products of this include …. ….. …… (3)
isocitrate dehydrogenase
NADH
CO2
alpha ketoglutarate
alpha ketoglutarate contains how many carbons?
5
in the TCA cycle alpha ketoglutarate is acted on by the enzyme …,.
this reaction also requires…
products of this reaction are… (3)
alpha ketoglutarate dehydrogenase
coenzyme A
NADh
CO2
succinyl coa
succinyl CoA contains how many carbons?
4
In the TCA cycle Succinyl CoA is acted on by the enzyme ….
this reaction also requires …. as a reactant
products of this reaction are ….. (3)
succinate thiokinase
GDP
Succinate
GTP
CoA
in the TCA cycle Succinate is acted on by the enzyme ….
this reactions requires what else as a reactant
products of this reaction are ?
succinate dehydrogenase
FAD
fumarate
FADH2
in the TCA cycle fumarate is converted to ….
Malate
in the last step of the TCA cycle …. is converted to ….. and …..
the enzyme required is ….
malate
oxaloacetate
NADH
malate dehydrogenase
alpha ketoglutarate requies what coenzyme to function ?
thiamine (vitamin B1)
regulation of the TCA cycle
when … levels are high relative to … this signals high energy requirement for the cell and therefore need to increase flux through the TCA cycle
ADP
ATP
…. activates isocitrate dehydrogenase in the TCA cycle
ADP
…. is a negative regulator of the TCA cycle
it is a negative allosteric inhibitor of …. enzyme
NADH
isocitrate dehydrogenase
inhibition of isocitrate dehydrogenase by ….
this leads to the accumlatin of isocitrate which favours the reformation of ….
…. is a negative allosteric inhibitor of the enzyme that formed it which is …
citrate then can be moved into the …. for ….
NADH
citrate
citrate
citrate synthase
cytoplasm
fatty acid synthesis
regulation of TCA cycle
oxidation of …. by the ETC, which is a regulator of the cycle, is important for ATP production but also continued availablility of … to facilitate redox reactions of the TCA cycle
NADH
NAD+
approximately ….% of amino acids for new protein synthesis recycled from protein breakdown
75%
……. cannot be stored so surplus to the needs to the body are broken down
amino acids
surplus …. cannot be stored - carbon skeleton recycled or oxidized for energy. …. group excreted as ….
amino acids
amino
urea
…. refers to the state where amount of nitrogen consumed is matched by the amount excreted
nitrogen balance
describe negative nitrogen balance?
what states can lead to a negative nitrogen balance ?
nitrogen excreted is greater than the amount of nitrogen consumed. Protein breakdown is occuring at a greater rate than protein synthesis (amino acids cannot be stored)
starvation - can be glucogenic or ketogenic
cachexia - severe and unintentional weight loss (cancer, congtestive heart failure, COPD)
dietary deficiency of essential amino acids - other amino acids that would have gone into making new proteins with the absent amino acids are instead degraded
describe positive nitrogen balance?
In what situations would this occur ?
protein consumption is greater than protein exceretion. Protein synthesis is occuring at a higher rate than protein breakdown
pregnancy
growing child
…. is an amino acid that can be derived from the addition of an amino group to oxaloacetate
…. is an amino acid that can be derived from the addition of an amino group to alpha ketoglutarate
aspartate
glutamate
non-essential amino acids can be derived from the ….cycle, …. pathway and … pathway
TCA
pentose phosphate pathway
glycolytic pathway
what is the acronym for the essential amino acids.
these must be consumed
what are the essential amino acids
these ten amino acids have long preserved life in man
Threonine
tryptophan
arginine
lysine
phenylalanine
leucine
isoleucine
methione
tyrosine is considered a non-essential amino acid, however can become essential in this diseased state ?
phenylketouria disease
removal of nitrogen from amino acids is a two step process
step 1: ….. with alpha ketoglutarate forming …. and …..
step 2: …. is deaminated through a … process involving NAD+
transamination
glutamate
alpha ketoacid
glutamate oxidative
common amino acid/alpha keto acid pairs
alanine/….
…./oxaloacetate
glutamate/…..
pyruvate
aspartate
alphaketoglutarate
… catalyze the transfer of an amino group from a amino acid to an ….
amino acid donor becomes a …. and amio acceptor (alpha ketoacid) becomes a ….
all transaminases utilize … as a cofactor. what vitamin is this derived from ?
transaminases
alpha ketoacid
alpha ketoacid
amino acid
PLP - pyridoxal phosphate
vitamin B6
the most common alpha ketoacids that act as amino group acceptors in transaminase reactions are ?? (2)
oxaloacetate - forming asparate
alpha ketoglutarate - forming glutamate
oxidative deamination of glutamate yields … , …. and ….
this reaction is catalyzed by …
this enzyme is reversible ? true or false
alpha ketoglutarate
NH4+ (ammonium)
NADH
glutamate dehydrogenase
true
glutamate dehydrogenase is present in the … of the cell
mitochondrial matrix
allosteric regulation of glutamate dehydrogenase
high …. ratio favours …. production
low … ratio favours … production
ATP/ADP
glutamate
ATP/ADP
alpha ketoglutarate
amino acids can be broadly classified as … and ….
… are those whose C skeleton can be converted to intermediates which can lead to net glucose production via …. pathway
… are those who C skeleton are converted to intermediates which cannot lead to … synthesis but can lead to synthesis of …. and ….
glucogenic
ketogenic
glucogenic
gluconeogenesis
ketogenic
glucose
fatty acid
ketone bodies
Fate of ammonium ion
some NH4+ utilized in … of … containing compoiunds
rest is converted to … for …
biosynthesis
nitrogen
urea
excretion
extraepatic tissue can breakdown amino acids but cannot process the … group
excess ammonium is therefore converted to … and … by the enzymes …. and …. , respectively
the glucose-alanine cycle is also responsible for moving NH4+ to the liver
amino
glutamate
glutamine
glutamate dehydrogenase (reductive amination)
glutamine synthetase
glucose- alanine cycle
in this cycle we get the conversion of … to … in extrahepatic tissue
in the liver … is converted to … and may be used in …. and the amino group enters the … cycle
pyruvate
alanine
alanine
pyruvate
urea
overview of the urea cycle
occurs in the …. (organ)
the first phase occurs in the …
the second phase occurs in the …
amino groups enter the cycle as : (2)
…. amino groups are released as urea
liver
miochondria
cytoplasm
citruline
aspartate
2
Urea cycle is regulated by the acitivity of the rate limiting enzyme ….
carbamoyl phosphate synthetase
the …. is regulated by the activity of the rate limiting enzyme carbamoyl synthetase
mitchondrial phase of the urea cycle
… and … enter the mitochondria.
….. converts glutamine to glutamate
… is acted on by … to form NH4+, NADH, and alpha ketoglutarate
NH4+, CO2 and …. are utilized in order to synthesize …. which is catalyzed by the enzyme …
…. condenses with … to form …. which is catalyzed by the enzyme
glutamine
glutamate
glutamate
glutamate dehyudrogenase
2 ATP
carbamoyl phosphate
carbamoyl phosphate synthetase
carbaboyl phosphate
ornitine
citruline
ornitine transcarbamoylase
cytosolic phase of the urea cycle
in the first step … condenses with … to form …. which requires the enzyme …
this reaction is requies ….
…. is then cleaved by …. to form …. and ….
…. is ceaved into …. and …. by ….
…. can now eneter back into the mitochondria and combine with carbamoyl phosphate to form citruline and the cycle can begin again
citruline
aspartate
arginosuccinate
arginsuccinate synthetase
ATP
Arginosuccinate
arginine
fumarate
arginosuccinase
arginine
ornitine
urea
ornithine
the rate limiting enzyme of the urea cycle is ….
…. is allosterically activated by … and not active wihtout the preseence of …
carbamoyl phosphate synthestase
carbamoyl synthestase
N -acetylglutamate
N-acetyl glutamate
… is an allosteric activator of carbamoyl phosphate synthetase, the rate limiting step in the urea cycle
… is synthesized from … and … when cellular … are high by the enzyme….
… enzyme is allosterically activated by ….
this signals high levels of free amino acids and the need to upregulate the urea cycle
N-acetylglutamate
N-acetylglutamate
acetyl CoA
glutamate
glutamate
N-acetylglumatae synthase
N-acetylglutamate synthase
arginine
clinical correlation: Urea cycle disorders
disorders of the urea potentially … because there is no … for urea synthesis
hyperammonemia can lead to …. disturbances and is also … toxic
deficits in any of the enzymes involved in the urea cycle can lead to to hyperammonemia
fatal
alternative pathway
acid/base
neurotoxic
treatment for Urea cycle disorders
- restrict ….
- supplement diet with… (amino acid)
- enrich diet with …
- supplement diet
- liver …
dietary protein
arginine - increase ornithine transcarbomyl transferase activity through increase ornitine. also activator of N-acetylglutmate synthase (N-aectylglutamate is a key regulator of carbamoyl phosphate synthetase)
alpha ketoacids
compounds that provide alternative means of nitrogen excretion - benzoate, phenylbuytrate
liver transplant
…. is a metabolic disorder characterized by the inability to synthesize tyrosine from phenylalanine
this metabolic disorder results from impairement of …. enzyme
… is a cofactor for this enzyme
if left untreated it can cause progressive …. , …. damage and ….
phenylketouria
phenylalanine hydroxylase
tetrahydrobiopterin (BH4)
neurological degeneration
brain
seizures
treatment of Phenylketouria
lifelong dietary … restriction and … supplementation
want level of … where protein synthesis is not affected but we do not get excess accumulation
…. is now an essential amino acid
phenylalanine
tyrosine
phenylalanine
tyrosine
what are the three branched chain amino acids ?
valine
leucine
isoleucine
metabolism of branched chained amino acids is inititaed in ….
there is specific brain chain ….. enzymes in … only, which convert the amino acids to …..
…. are then degraded by …. which generates….
muscle
aminotransferases
muscle
alpha ketoacids
branched chain alpha ketoacids dehydrogenase (BCKDH)
isovaleryl CoA
….. disease is characterized by a deficiency of the enzyme branched chain alpha ketoacid dehydrogenase
maple syrup disease
malpe syrup disease is due to a deficiency of functional ….. enzyme
branched chain alpha ketoacid dehydrogenase
treatment of maple syrup disease
Dietary restriction of ….
branched chain amino acids to minimum level required for growth
glutamate dehydrogenase catalyzes a reversible reaction
what condition favours the formation of glutamate from … and ….?
what condition favours the formation of … and … from glutamate ?
alpha ketoglutarate
NH4+
elevated cellular ATP (energy abundance) - favours anabolism, amino acid and protein synthesis
alpha ketoglutarte
NH4+
low cellular energy (high ADP or GDP) - alpha ketoglutartae can be oxidized via the TCA cycle
…. is a key enzyme in controlling flow of nitrogen into biological molecule. …. serves as an amino group donor for the synthesis of many amino acids, nucleottides and amino sugars.
glutamine synthetase
glutamine
….. enzyme is regarded as the cells nitrogen receptor
glutamine synthetase
…. enzyme is subject to cumulative feedback inhibition by atleast 8 different regulators
these regulators require amino group from …. (amino acid) for synthesis
these include:
glutamine synthetase
glutamine
AMP
CTP
histidine
tryptophan
carbamoyl phosphate
glucosamine-6-phosphate
