biochem Flashcards
3 (+1) enzymes
what are the 3 steps in glycolysis that are the main targets for regulation
and why
all these steps are irreversible
1. hexokinase:
first step of glycosis, glucose is trapped to carry out glycolysis
2. phosphofructokinase-1:
entry point to glycolysis, commitment step
3. pyruvate kinase:
last step of glycolysis, ATP produced
one other step where there is also (minor) regulation is phosphoglycerate kinase — ATP generated
so if u think abt it, all the steps involving “kinase” enzyme is regulated
which part of the cell does glycolysis occur in
cytoplasm
how much ATP is generated from each molecule of glucose during glycolysis
2 ATP
2 ATP used, 4 ATP produced
what substrates are required during glycolysis
NAD+ and Pi
what does “shunt”
in hexose monophosphate (HMP) shunt
refer to
rearrangement during non-oxidative phase
→ excess xylulose-5-P and ribose-5-P converted to fructose-6-P and glyceraldehyde-6-P
⇒ recycled back to glycolysis
relate to its phases
what are the functions of HMP shunt
- generate NADPH during oxidative phase
- generate ribose-5-P for nucleotide synthesis during non-oxidative phase
in which of the following cells and tissues
are the HMP shunt least likely to be active in?
A) Adipose tissue
B) Adrenal cortex
C) Red blood cells
D) Skeletal muscle
E) White blood cells
D) Skeletal muscle
HMP shunt is active in tissues with high usage of NADPH, such as
* adipocytes: fatty acid synthesis
* liver: fatty acid synthesis and drug metabolism
* adrenal cortex and gonads: steroid synthesis
* RBC: gluthathione reduction
* WBC: generation of superoxide
- drug metabolism: conjugation of drug
→ decrease activity and increase solubility - gluthathione reduction: which is oxidised in process of neutralising ROS like H₂O₂
- generation of superoxide: in order to kill bacteria
how does G6PD deficiency result in RBC haemolysis
decrease production of NADPH
→ gluthathione is not kept in reduced state
→ unable to neutralise ROS
→ proteins in RBCs are oxidised
→ decrease in membrane plasticity
⇒ haemolysis
what is 1 possible benefit of G6PD deficiency
decrease production of NADPH
→ which is used by malarial parasites for survival and replication
⇒ confer resistance to malaria infections
which part of the cell does the HMP shunt function in
cytoplasm
relate to steps in glycolysis
what are the 3 main steps in gluconeogenesis
- pyruvate → phosphoenolpyruvate (PEP)
- fructose-1,6-biphosphate (fructose-1,6-P2)
→ fructose-1,6-P - glucose-6-P → glucose
reverse of the 3 key steps in glycolysis:
1. glucose -> glucose-6-P:
first step of glycosis, glucose is trapped to carry out glycolysis
2. fructose-1,6-P -> fructose-1,6-P2:
entry point to glycolysis, commitment step
3. PEP -> pyruvate:
last step of glycolysis, ATP produced
which part of the cell does the gluconeogenesis occur in
- mainly cytoplasm
- first step of glycolysis: mitochondria
- last step of glycolysis: endoplasmic reticulum
and why
which tissues does gluconeogenesis primarily occur in
liver and kidney
<- glucose-6-phosphatase
(enzyme involved in last step)
is ONLY present in gluconeogenic tissues (liver and tissue)
also recall: this last step occurs in ER of cell!
what is the order of sources for maintaining blood glucose levels?
(first -> last)
* dietary carbohydrates
* gluconeogenesis
* glycogen breakdown
- dietary carbohydrates: up to 4 hours after meal
- gluconeogenesis: up to 24 hours after meal
- glycogen breakdown: anything MORE than 24 hours after meal
and which one contains the MOST amt of glycogen
which organs are the main storages of glycogen
- Liver and muscle
- muscle contains the most
glycogen is only 1-2% of weight of muscle (lesser than the 5-6% in liver),
but muscle tissue has a large total mass
2 diff ones, based on organ
what are the functions of glycogen
- MUSCLE glycogen provides short term source of energy during exercise
<- via glycolysis, which it enters as glucose-6-phosphate - LIVER glycogen provides short term source of glucose during fasting
(recall: <24hr after meal)
<- via free glucose
hint: the activated building block
what is the building block for glycogen synthesis
UDP-glucose
what is the major point of regulation for glycogen synthesis
lengthening of glycogen primer
via glycogen synthase
by forming a-1,4 linkages
the step regulated in both glycogen synthesis and breakdown
involves a change in length of the glycogen chain
what is the major point of regulation for glycogen breakdown
shortening of glycogen primer
via glycogen phosphorylase
by cleaving a-1,4 linkages
the step regulated in both glycogen synthesis and breakdown
involves a change in length of the glycogen chain
what is the function of branching
- increases sites for synthesis and degradation
- enhances solubility
same step, but 2 diff enzymes for diff organs
in which step are there 2 different enzymes involves and why
step in which
glucose -> glucose-6-phosphate
* all other tissues (e.g. muscle tissue) catalyses rxn via hexokinase
* liver catalyses it via glucokinase
which is NOT inhibited by G6P (i.e. NO product inhibition)
-> liver can continuously convert glucose to G6P
and thus carry out glycogen synthesis
=> allow liver to do its role of regulating blood glucose levels
which apolipoprotein is required for proper assembly of nascent chylomicrons
within enterocytes
ApoB-48
produced by enterocytes themselves
do nascent chylomicrons enter blood circulation directly
No!
* enterocyte -> lymphatic system -> blood circulation
* due to the chylomicrons being too big to pass through pores in blood capillaries,
but being able to fit through larger pores in lymphatic capillaries
and where
how do nascent chylomicrons become mature chylomicrons
- in blood
- when HDLs transfer ApoE and ApoCII to nascent chylomicrons
function of ApoCII
acts as cofactor of lipoprotein lipase (LPL)
-> activates LPL
-> conversion of TG into FAs and glycerol
(-> chylomicrons thus become chylomicron remnants)
function of ApoE
allow chylomicron remnants to bind to ApoE receptors on hepatocytes
-> undergo endocytosis
and then degradation in cell
=> allow dietary cholesterol/cholesterol esters in chylomicron remnants to be delivered to liver
and where do each come from
what apolipoproteins does a mature VLDL have
- ApoB100: since nascent VLDL was synthesized in liver
- ApoE and ApoCII: transferred from HDL
breakdown process, fate of products
how does VLDL transport TG to extrahepatic tissues
ApoCII activates LPL at capillary walls of tissues
→ LPL converts TG to FAs and glycerol
⇒ FA are taken up by tissues,
(muscle: FA is oxidised to generate ATP
adipose tissue: FA is converted to TG for storage)
while glycerol is taken up by liver
what happens to VLDL after TG delivery
- becomes intermediate-density lipoprotein (IDL)
- release TG again
- EITHER returns to liver via ApoE receptors
OR becomes low-density lipoprotein (LDL)
pathogenesis of alcoholic fatty liver disease
(2 sides:
1) TG synthesis
2) VLDL synthesis and secretion)
- VLDL synthesis and secretion:
ethanol is metabolised to acetaldehyde in liver via:
i) alcohol dehydrogenase (ADH) in cytoplasm
ii) microsomal ethanol oxidising system (MEOS) in ER
→ acetaldehyde is toxic and damages cellular biomolecules (e.g. proteins, phospholipids, etc)
→ LIVER DAMAGE
→ impaired synthesis and secretion of VLDL - TG synthesis:
NAD+ is converted to NADH in the process of ethanol -> acetaldehyde
→ reduced cellular NAD+ to act as cofactor in FA β-oxidation
→ reduced FA β-oxidation
→ accumulation of FA which are converted into TG
Overall: rate of synthesis of TG > rate of VLDL synthesis and secretion
→ accumulation of TG
⇒ fatty liver
stimulus, hormones involved, subsequent transport
how are fatty acids released from adipocytes
fasting state
-> higher levels of glucagon
-> LIPOLYSIS: glucagon activates hormone sensitive lipase (HSL)
which converts TG to FAs and glycerol
-> FAs are released and bound to albumin in blood and transported to liver or muscle,
while glycerol is transported to liver
function of FA β-oxidation
- produces acetyl-CoA which enters TCA cycle for ATP production
- produces FADH2 and NADH which transfer electrons to ETC
for ATP synthesis
what is the rate-limiting step in FA β-oxidation
carnitine-mediated entry process
enzymes involved, locations
explain the carnitine-mediated entry process step of FA β-oxidation
- conversion of fatty acyl-CoA -> fatty acyl-carnitine
by CPT1
in mitochondria intermembrane space - movement of fatty acyl-carnitine
across inner mitochondrial membrane,
facilitated by acyl-carnitine translocase - conversion of fatty acyl-carnitine -> fatty acyl-CoA
by CPT2
in mitochondria matrix
does ketogenesis occur in a
fed or fasted state
fasted!
* high glucagon
-> activation of HSL
=> increase lipolysis in fatty tissues
* high glucagon and low insulin
-> inhibition of ACC
-(along with high cellular FA conc)-> increase FA β-oxidation in liver
-> high levels of acetyl CoA
-> CANNOT enter TCA cycle efficiently due to low oxaloacetate availability
=> directed to ketogenesis
high glucagon also stimulates gluconeogenesis
(recall: glucose supply during long fast is gluconeogenesis!)
-> more oxaloacetate used during gluconeogensis
=> lower oxaloacetate availability
what substrates make up ketone bodies
- acetoacetate
- β-hydroxybutyrate
- acetone
function of ketone bodies
exported (out of liver) for use by extrahepatic tissues
as fuel (i.e. ATP generation)
how is it used as fuel?
acetoacetate and β-hydroxybutyrate are converted back to acetyl CoA (ketolysis)
→ used in TCA cycle to generate ATP
specifically which part of which organ
where does ketogenesis occur
mitochondria of liver cells
where does ketolysis occur
mitochondria
what is the advantages of ketolysis in each tissue
what are the main extrahepatic tissues which take up ketone bodies
-
brain
(under conditions of PROLONGED starvation)
← brain does NOT use FAs for energy production - skeletal and cardiac muscle
← ketone bodies can enter mitochondria efficiently to support energy production independent of carinitine shuttle system
do ketone bodies require carrier for transport
no
bcos they are small water-soluble molecules
→ readily dissolves in blood for transport
Ketolysis does not occur in the liver.
True or False?
True!
liver does NOT express transferase required
Why do patients with type 1 diabetes mellitus exhibit ketoacidosis
hint: type 1 DM leads to destruction of insulin producing β-cells of pancreas
low insulin and high glucagon
→ increase lipolysis in adipose tissues
→ increase release of FA
→ increase FA β-oxidation in liver
→ increase acetyl CoA
→ increase ketogenesis
→ rate of ketogenesis > rate of ketolysis
→ high levels of ketone bodies in blood
⇒ ketoacidosis (since ketone bodies are acidic)
also result in ketonuria
as ketone bodies are water soluble
→ can be excreted in urine
how does a ketogenic diet reduce fat mass
low carbohydrate intake
→ low blood glucose
→ high glucagon levels
→ promotes lipolyiss
⇒ reduce fat mass
why can cholesterols only be transported in blood by lipoproteins
lipophilic and is thus not soluble in blood
what are the 2 enzymes involved in
stage 1 (mevalonate synthesis)
of cholesterol synthesis
- HMG-CoA synthase in cytoplasm
- HMG-CoA reductase anchored on ER membrane
what is the rate-limiting step of cholesterol synthesis
conversion of HMG-CoA -> mevalonate
via HMG-CoA reductase
also the committed reaction step
both ketogenesis and cholesterol synthesis occur in liver and use HMG-CoA.
how is competition for HMG-CoA prevented?
cellular compartmentalisation
* ketogenesis occurs in mitochondria
* cholesterol synthesis occurs in cytosol
what is hepatic cholesterol used for in liver
synthesis of bile acids and bile salts
what is hepatic cholesterol used for in extrahepatic tissues
- component of cell membranes
- vit D
- steroid hormones
how is primary bile acids synthesis regulated
negative feedback mechanism,
where primary bile acids (pdt) suppress expression of 7a-hydroxylase (enzyme involved)
→ prevents wasteful overproduction
differences between bile acid and bile salts
- bile acid: protonated
- bile salt: deprotonated
=> higher solubility and act as better emulsifiers
how do primary bile acids become primary bile salts
via conjugation
(with taurine or glycine)
how do 1º bile salts become 2º bile acids
via deconjugation and dehydroxylation
by intestinal bacteria
describe the recycling of bile acid
mediated by enterohepatic circulation,
in which 1º bile salts and 2º bile acids are reabsorbed in terminal ileum into portal circulation
→ travel via portal vein to liver
→ taken up by hepatocytes
(→ 2º bile acids are reconjugated)
⇒ re-secreted into bile
2º bile acids do NOT need to be rehydroxylated as they are still functional in their dehydroxylated form for digestion and absorption
which of the following statements regarding synthesis of vit D is true?
A) process only involves biosynthesis, and none of its substrates can be obtained from our diet
B) the final step occurs in the liver
C) calcitriol is the active form of vit D3
D) conversion of 7-dehydrocholestrol, the immediate precursor of cholesterol, to vit D3 occurs at kidney
C) calcitriol is the active form of vit D3
* (A): vit D3 can also be obtained from diet, from foods such as fish and eggs
* (B): vit D3 is converted to calcitriol (last step) at kidney
* (D): conversion of 7-dehydrocholesterol to vit D3 occurs at the skin and requires UV light
what is the fate of LDL
- return to liver via LDL receptors (ApoB-100)
- OR delivers cholesterol to extrahepatic tissues
which of these apolipoproteins (B100, E, CII) are found on
* VLDL
* IDL
* LDL
respectively?
- VLDL: all 3
- IDL: ApoB-100 and ApoE
- LDL: ApoB-100
- why do they keep “losing” apolipoproteins?
bcos as they lose TG at each stage
→ their density increases
⇒ dissociation/transfer of an apolipoprotein - ApoCII dissociates from VLDL,
while ApoE is transferred to HDL
mature chylomicron and VLDL differ in which apolipoproteins
Both have ApoC-II and ApoE
* mature chylomicron: ApoB-48
* VLDL: ApoB-100
ApoB-48 and ApoB-100 come from the same gene,
but ApoB-48 is a truncated version of ApoB-100,
thus does NOT have portion which binds to hepatocyte receptors
what is the enzyme that removes TG from IDL and hydrolyses it
hepatic triglyceride lipase (HTGL)
does not require apolipoprotein as a cofactor, unlike LPL!
role of LDL in atherosclerosis
LDL is trapped at damaged site of damage
(at inner wall of artery)
and becomes oxidised
→ endothelial cells in response secrete cytokines to induce an accumulation of monocytes
→ monocytes transform into macrophages which internalise oxidised LDL
→ macrophages become foam cells
⇒ which accumulate to form plaque,
thus thickening and hardening arterial wall
smooth muscle cells of artery then replicate and migrate to form a firm cap covering the plaque
why is HDL called the “good cholesterol”
mediates reverse cholesterol transport by
taking up cholesterol from cell membranes of extrahepatic tissues
-> converts C to CE
-> resultant lipid-rich HDL (called HDL2)
1. binds to SR-B1 receptor with ApoA1 on liver and release C and CE to it
2. exchange CE for TG with VLDL
-> converting VLDL to IDL and some to LDL
-> IDL and LDL transport CE back to liver
-> resulting lipid-poor HDL is called HDL 3
note: the transfer of cholesterol from HDL to liver
does NOT require endocytosis of WHOLE particle,
unlike IDL, LDL and chylomicron remnants,
which undergo receptor-mediated endocytosis, followed by lysosomal degradation!
what function do phospholipids have to play in relation to neurons
key component of myelin sheath of neurons
specifically the phospholipid sphingomyelin
include prostaglandins, thromboxanes and leukotrienes
main function of eicosanoids
act as autocrine/paracrine hormones
=> act over SHORT distance and time
autocrine: act on same cell that produced them
paracrine: act on neighbouring cells in local envt
what are essential fatty acids
fatty acids that are
* NOT synthesised by body
* must be obtained from diet
what are the 2 essential fatty acids
and what do they form
- Linoleic acid — LA (omega-6 FA)
⇒ produce arachidonic acid (AA) - α-Linolenic acid — ALA (omega-3 FA)
⇒ produce docosahexaenoic acid (DHA)
describe arachidonic acid (AA) metabolism
stimuli
→ activation of phospholipase A2
→ translocation from cytosol to cell membrane
→ cleaves membrane phospholipids containing AA
⇒ release AA into cell
specific drugs
which enzymes are the drug targets of eicosanoids metabolism
- phospholipase A2: inhibited by steroids
- cyclo-oxygenases (COX): inhibited by NSAIDs
- lipooxygenase: inhibited by zileuton
cause of aminoacidurias
failure in
* absorption of certain AAs from intestine
* reabsorption of certain AAs from kidneys
what is the 1st step of amino acid metabolism
conversion to KETO acids via
* oxidative deamination: glutamate
* transamination: most amino acids
* non-oxidative deamination: certain amino acids
(e.g. serine)
importance of converting amino acids into keto acids
- keto acids (+ NADH) can be used for energy production
(e.g. pyruvate -> glycolysis, oxaloacetate -> TCA cycle) - synthesis of NON-ESSENTIAL amino acids
other than keto acids,
what are the other products of oxidative deamination
- NADH or NADPH
(depending on whether NAD+ or NADP+ was used as substrate0 - NH4+
rxn: L-glutamate -> α-Keto glutarate
what is the enzyme involved in oxidative deamination
L-glutamate dehydrogenase
rxn: L-glutamate -> α-Keto glutarate
substrates, products, enzyme, co-factor
describe transamination
- substrates: amino acid A, keto acid B
- products: keto acid A, amino acid B
- enzyme: aminotransferase (transaminase)
- co-factor: PyridoxaL Phosphate (PLP)
← derived from vit B6
example of transamination
- substrates: aspartate (amino acid A),
a-ketoglutarate (keto acid B) - products: oxaloacetate (keto acid A),
glutamate (amino acid B) - enzyme: ASpartate aminoTransferase (AST)
importance of transamination
- linked to oxidative deamination = transdeamination
- funnel amino groups (containing nitrogen) into glutamate
(transamination)
for conversion into ammonia
(oxidative deamination)
example of transdeamination
- alanine -> pyruvate
- ALanine aminoTransferase (ALT)
specify which enzymes
how can enzymes involved in transamination
be of clinical diagnostic value
-
ALanine aminoTransferase (ALT)
and ASpartate aminoTransferase (AST) -
intracellular ALT and AST are released into blood when cells are damaged
⇒ raised levels seen in necrosis or disease
what happens next in ammonia excretion process
after glutamate is formed?
- peripheral tissue cell: converted to glutamine
- which is transported out of cell using specialised transporters
and then transported in blood to site of excretion (e.g. kidney) -
kidney cell: broken down into glutamate + NH3
then glutamate further broken down into α-KG + NH3 - NH3 crosses cell membrane and diffuses into urine
- where it combines with H+ to form NH4+,
and is now trapped (i.e. cannot diffuse back) - thus excreted in urine
how does physiological pH help with ion-trapping
- physiological pH is 7.4
- pKa of NH4+ ↔ NH3 + H+ is 9.3
thus NH4+ formed in urine is unlikely to dissociate
recall! if pKa = x for eqm: A ↔ B
* pH < x favours formation of A
* pH > x favours formation of B
why do we not excrete NH3/NH4+ as our main nitrogenous excretory product
high NH4+ conc
→ eqn of glutamate ↔ α-KB will be shifted to left
→ depletion of NADH and NADPH
⇒ impede energy production and biosynthesis
which organ is the main site of the urea cycle
liver
which parts of the cell does the urea cycle occur in
- mitochondria: first 2 steps
- cytosol: rest of the steps
why not ammonia itself
why is the main route of ammonia disposal through urea formation in the urea cycle
- ammonia is neurotoxic
- urea is much more soluble than ammonia
→ impt for terrestial creatures (e.g. mammals) which have limited access to water
in comparison, main excretory product in birds is ammonia
what cpds link urea cycle and TCA cycle
fumarate generated in urea cycle
-> forms oxaloacetate
-> EITHER enters TCA cycle
OR generate aspartate
which enters urea cycle
Any urea enzyme defect results in hyperammonemia.
True or False?
True
difference between ketogenic and glucogenic amino acids
potential of forming
* ketone bodies (ketogenic)
* glucose (glucogenic)
esp under starvation conditions
which AAs are purely ketogenic
- leucine (Leu)
- lysine (Lys)
What are the two main functions of the glucose-alanine cycle?
- Provides substrate for gluconeogenesis:
Muscle protein breakdown
→ amino acids (including alanine)
→ alanine travels to liver
→ converted to pyruvate
⇒ used for gluconeogenesis -
Removes ammonia safely from muscle:
Muscle protein breakdown
→ amino acids
→ which transfer their NH3 to α-KG
which then becomes glutamate
(transamination)
→ glutamate then transfers it NH3 to pyruvate
which then becomes alanine
(transamination)
→ alanine travels to liver, transporting ammonia with it
→ and then transfers its NH3 to α-KG
which then becomes glutamate
(transamination)
→ glutamate enters urea cycle
⇒ urea produced and excreted
muscle protein breakdown usually happens during long periods of starvation
→ produce glucogenic and ketogenic AAs
which can be converted into glucose and ketone bodies respectively
for energy production
+ possible drawback
what do muscles use for energy
during SHORT bursts of intense activity
ADP recycling
* 2 ADP -> ATP (+ AMP)
* ammonia produced and has to be removed
AMP also has a use!
It stimulates energy-producing processes (e.g. glycolysis)
and inhibits energy-consuming processes (e.g. cholesterol synthesis)
which is required in the diet,
essential or non-essential amino acids?
essential amino acids
bcos body cannot synthesize from simple precursors
OR cannot synthesize enough for its own bodily
needs
semi-essential amino acid (arginine):
non-essential under normal conditions,
but becomes essential during certain stressful situations or in specific physiological states
when the body cannot produce it in sufficient quantities
how does anti-malarial drugs
precipitate the development of anaemia
in patient with G6PD deficiency
increase ROS
recall that NADPH is required in many cells and tissues
why does G6PD deficiency
present with adverse effects related to RBCs only
RBCs do NOT have nucleus
→ cannot carry out compensatory increase in synthesis of G6PD enzymes
explain the clinical findings
deficiency in which enzyme
will lead to hypoglycaemia upon waking,
enlarged liver
and elevated pyruvate and lactate levels?
glucose-6-phosphatase
(Glycogen Storage Disease Type I - Von Gierke disease)
* prevents export of glucose from glycogenolysis and gluconeogenesis
⇒ fasting hypoglycaemia
(since glycogenolysis and gluconeogenesis are main sources which maintain fasting blood glucose lvls)
* glucose begins to accumulate in liver as glucose-6-P
→ increaed glucose-6-P levels stimulates glycogen synthase and inhivits glycogen phosphorylase
→ glycogen begins to accumulate abnormally within liver
⇒ hepatomegaly
* glucose-6-P (due to increased levels) is shunted towards glycolytic pathway
⇒ overproduces pyruvate
(elevated pyruvate levels in blood)
⇒ converted to lactate under anaerobic conditions
(elevated lactate levels in blood)
* glucose-6-P is also shunted towards HMP pathway
→ overproduces ribose-5-P
→ more purine synthesis and thus breakdown
⇒ overproduction of uric acid
(elevated uric acid levels in blood)
- does not accumulate as glucose-6-P bcos it is soluble and thus cant accumulate, while glycogen is a macromolecule and thus its bulk physically enlarges the liver
- anaerobic conditions is not due to lack of oxygen availability, but due to mitochondrial capacity (to carry out oxidative phosphorylation) being maxed out
why should a patient
with glucose-6-phosphatase deficiency
avoid intake of sucrose and milk
further increase glucose-6-P as
* galactose (from milk) is directly converted to glucose-6-P
(via galactokinase)
* fructose (from sucrose) is converted to DHAP
(via fructokinase),
which is then converted to glucose-6-P via glycolysis
key reactions in phase I detoxification
- oxidation
- hydrolysis
- reduction
key enzymes in phase I detoxification
(and the reactions they are involved in)
- Cytochrome P450s (CYPs):
hydroxylation and epoxidation rxns
(oxidation) - Esterases:
hydrolysis rxn
hydroxylation and epoxidation: incorporate one O atom into substrate
* hydroxylation: XH -> XOH
* epoxidation: X -> XO
hydrolysis: cleavage of ester bonds (COO, i.e. O-C=O)
(O-C=O -> A-OH + O=C-B)
function of phase I detoxification
render the xenobiotic a suitable substrate for phase II reaction
and how
what product formed in phase I detoxification is possibly toxic
epoxide
* very reactive
and needs to be converted to less reactive compounds
* react with DNA (covalent bond)
-> form DNA adduct
-> lead to mutations of genes in cells
=> cancer
* react with proteins
-> form adducts
=> loss of function and cellular injury
function of phase II detoxification
form ionic polar products
which can be easily excreted
must the substrate for phase II detoxification
be a product from phase I?
No!
if substrate has functional group alr
-> no need for phase I reaction
=> can directly undergo phase II reaction
functional groups: -OH, -COOH, -NH, -SH
main conjugation reactions involved in phase II detoxification
(and enzymes involved)
- glucuronidation: UDP-glucuronosyltransferase (UGT)
- sulphation: sulfotransferase (SULT)
- glutathione conjugation: glutathione S-transferase (GST)
- acetylation: N-acetyl transferase (NAT)
