Biochemistry Flashcards
Lecture 1 - Glycolysis Lecture 2 - Lipid Catabolism Lecture 3 - Amino acid catabolism
what is glycogenesis?
= synthesis of glycogen from glucose
what is glycogenolysis?
= breakdown of glycogen to form glucose
what is gluconeogenesis?
= de novo synthesis of glucose from metabolic precursors (lactate, amino acids, glycerol) is the way time
what is glycogen?
= main storage form of glucose in liver and muscle cells.
when is liver glycogen broken down? and why is released?
= between meals and released to maintain blood glucose levels for red blood cells and brain
Yes or No.
Is muscle glycogen available for maintenance of blood glucose levels?
= NO.
what does muscle glycogen do?
= provides energy via glycolysis & TCA during bursts of physical activity
what are 3 sources of blood glucose?
1) dietary
2) glycogenolysis
3) gluconeogenesis
what fluctuates dependent upon meal times?
= glycogenolysis
what is the primary source of glucose overnight when hepatic glycogen is depleted?
= glyconeogenesis
is glycogen a polymer or monomer?
= polymer consisting of glucose molecules
what are the glucose molecules in glycogen joined by?
= alpha 1-4 glycosidic links
how are branches introduced to glycogen structure?
= alpha 1-6 glycosidic links
what can glucose residues only be added to?
can only be added to an existing glycogen chain
what is required for glucose residue to bind to glycogen chain?
= a glycogen ‘primer’ containing at least 4 glucose residues
what is the primer covalently attached to?
a protein called glycogenin
liver specific protein
GLYCOGEN SYNTHESIS
how is glucose converted to glucose-6-phosphate?
by ATP being hydrolysed to ADP
and
the enzyme hexokinase
GLYCOGEN SYNTHESIS
how is glucose-6-phosphate converted to glucose-1-phosphate?
by enzyme phosphoglucomutase
GLYCOGEN SYNTHESIS
how is glucose-1phosphate converted to UDP-glucose?
by UDP glucose pyrophosphorlyase
and
hydrolysis of ATP and addition of UTP
GLYCOGEN SYNTHESIS
how is UDP-glucose is converted to glycogen?
by glycogen synthase.
in UDP-glucose, what are simple precursors first converted to?
activated intermediates
what can UDP glucose be thought as?
an activated form of glucose
ATP and acetyl CoA are activated forms of phosphate & acetate
what does the phosphate ester linkage in a nucleotide sugar release?
releases free energy on hydrolysis
what does glycogen synthase do?
synthesises glucose from UDP-glucose
- it adds one glucose molecules to glycogen at a time
what can glycogen synthase only do?
only extend the chains of glycogen
it cant start new molecules
Yes or No.
Can glycogen synthase introduce branches?
= NO.
what is the rate limiting enzyme of glycogenesis?
= glycogen synthase
what is an example of a branching enzyme?
what does it do?
= transglycosylase
= introduces an Alph 1-6 glycosidic branches into glycogen
approximately every 10 glucose residues
what is glycogenolysis catalysed by?
= glycogen phosphorylase
describe the pathway of glycogenolysis?
[glucose]n + phosphate
INTO
glucose-1-phosphate + [glucose]n-1
what does glycogen phosphorylase do?
cleaves one glucose molecule of ends of glycogen at a time
what is glucose-1-phosphate converted to and what converts it?
= glucose-6-phosphate
converted by
= phosphoglucomutase
in the liver, as a continuation of glycogenolysis what happens to glucose-6 phosphate?
de-phosphorylated
and resulting glucose released into blood stream via GLUT2 transporter
in skeletal muscles, as a continuation of glycogenolysis, what happens to glucose-6 phosphate?
CANNOT be de-phosphorlyated but instead provides energy via glycolysis & TCA cycle
Yes or No.
Does de-branching require additional enzymes?
YES
what is gluconeogenesis?
= synthesis of glucose within body from precursor substrates
what are 3 examples of precursors of gluconeogenesis?
1) lactate = synthesised by skeletal muscles under anaerobic conditions
2) amino acids = derived form muscle proteins by proteolysis
3) glycerol = derived from triglycerides by lipolysis in adipose tissue
where does the energy come from in gluconeogenesis?
= from oxidation of fatty acids released from adipose tissue
where does gluconeogenesis occur?
= in liver, small amounts in kidney
REMIDNER
- what are 3 irreversible reactions in glycolysis?
- hexokinase
- phosphofructokinase
- pyruvate kinase
what is required for gluconeogenesis?
= four unique liver enzymes
what does gluconeogenesis proceed?
= proceeds via synthesis of oxaloacetate in mitochondria
- the TCA cycle intermediate which accepts acetyl groups
does gluconeogenesis consume energy?
yes it consumes energy
in gluconeogenesis, how is pyruvate converted to glucose?
2pyruvate + 4ATP + 2GTP + 2NADH + 4H+ + 6H20
GOING TO
glucose + 4ADP + 2GDP + 6Pi + 2NAD+ + 2H+
what does ATP hydrolysis drive?
an unfavourable reaction
what is the name of the cycle which converts lactate to glucose?
= cori cycle
what transport lactate to liver?
blood
what does the liver do?
= converts lactate back to glucose
what does the Cori cycle do?
buys time and shift metabolic burden from muscle to other organs
what is glycolysis and gluconeogenesis known as?
reciprocal regulation
meaning, when one is highly active, the other is inhibited
what 5 things are involved in reciprocal regulation?
1) hormonal regulation (glucagon, insulin)
2) high AMP or ADP (means low energy)
3) high ATP (high energy)
4) fructose 2,6-biphosphate
(high in fed state, low in starved state)
5) citrate, alanine and acetyl Co-A
(high when intermediates or building blocks are abundant)
LECTURE 2 - LIPID CATABOLISM
LECTUURE 2 - LIPID CATABOLISM
what does increased fat intake without appropriate energy expenditure leads to?
1) increased number of adipocytes
2) more fat in adipocytes
= obesity
what 2 factors does control of energy balance depend on?
1) genetically linked factors
e,g. protein messengers regulating appetite
2) environmental factors
e. g. food abundance, fashionable foods
what are fats required?
1) as energy source
2) for essential fatty acids
- some polyunsaturated fatty acids can’t be made by body
- deficiencies can lead to membrane disorders, increased skin permeability, mitochondrial damage
3) for fat soluble vitamins
- vitamins A, D, E, K
absorption of these vitamins is closely linked to that of fat
stored in body fat
what happens if fat intake or absorption is inadequate?
= secondary deficiencies occur
what are 3 different types of lipids?
1) simple lipid
- fatty acids
- triglycerides
- waxes
2) compound lipids
- phospho
- glyco-lipids
- lipoprotein
3) steroids
- cholesterol
- steroid hormones
what are lipids predominantly?
What do they usually contain?
Are lipids soluble in water?
Predominantly hydrocarbon.
Usually contain long chain fatty acids.
Insolube in water.
where are triglycerides the main energy storage from?
adipose tissue
are triglycerides hydrophobic or phillic?>
hydrophobic
are triglycerides high or low energy yield per gram?
high energy yield per gram
what dot triglycerides consist of?
- glycerol
- 3 fatty acids
what are fat acids usually in terms of their chain appearance and rings?
= straight chains
= aliphatic (no rings)
- usually contain an even number of C atoms.
what are the 3 things that fatty acids can be?
how do double bonds in fatty acids usually form?
1) saturated (no double bonds)
2) unsaturated (one double bond)
3) polyunsaturated (several double bonds)
- occur in small amounts
cis configuration
what are the 3 common main natural fats acids?
1) palmitic acid
2) stearic acid
3) oleic acid
can polyunsaturated fatty acids be synthesised by the body?
what are polyunsaturated fatty acids usually?
many cannot be synthesised by body.
- essential fatty acids
e. g. linoleum acid
what do fatty acids have on their carbon 1?
Note - what is an alpha carbon?
carboxyl group
OR
- carbon adjacent to carboxyl group is an alpha carbon
- C furthest away is Pi carbon
- carbon adjacent to a carboxyl group
when are fatty acids liquid at room temperature?
fatty acids with up to 8 carbon atoms.
- longer ones are solid
what lowers melting point in fatty acids?
= double bonds
what sort of fat contains a large proportion of unsaturated fatty acids = liquids?
= plant fats
what do animal fats contain?
= mostly palmitic and stearic acid = solid
what are 3 main products of fat digestion?
1) glycerol (absorbed by intestinal epithelial cells)
2) fatty acids
3) mono-glycerides
where is the fat absorbed into?
- into mucosal cells of intestine
= Short and medium length fatty acids enter portal blood
= longer chain FAs and monoglycerides are re-synthesised to triglycerides
what are chylomicrons?
= products of fast digestion that are coated with a layer of protein, phospholipid, cholesterol
what do chylomicrons enter?
what happens when chylomicrons at muscle and adipose tissue?
what happens to the free fatty acids at this point?
lymph then blood stream.
at muscle and adipose tissue chylomicrons are attacked and cleaved by lipoprotein lipases.
Free fatty acids are;
- resynthesised into triaclyglycerols
- oxidised to provide energy
- depends on amount available
what is lipolysis?
= breakdown of lipids
where is fat stored?
in adipose tissue
in lipolysis of stored fats, how are they initially cleaved?
by hormone sensitive lipase (e.g. adrenaline sensitive)
= releases free fatty acids and glycerol
= occurs when energy is needed
what do fatty acids need to be converted to before they can be oxidised to generate energy?
an d where does this conversion take place?
- converted to CoA derivates
= conversion takes place in cytoplasm
describe the pathway of fatty acid conversion to acyl-CoA?
and what does this conversion required?
Fatty acids + CoA = acyl-CoA
required 2ATP
where can further oxidation of fatty acids occur?
in mitochondrial matrix
- needs to be transported in mitochondria by special carrier mechanism
what happens in the cytoplasm in the carnitine shuttle?
- fatty acids are transferred from acyl-CoA to carnitine
what does the acyl-carnitine transporter do in the inner membrane of the carnitine shuttle?
= facilities anti port of acyl-carnitine into mitochondrion and carnitine out
what is the net result in the carnitine shuttle?
= acyl-CoA located in mitochondria matrix
what is beta oxidation?
cycle of reactions in mitochondrial matrix
how many steps are there in beta oxidation and describe the products of each step?
Four steps
= 1 acetyl Co-A
= 1 FADH2
= 1 NADH + H+
= 1 fatty acyl-CoA shortened by 2 carbon atoms
in the yield of Beta oxidation, how many times is the cycle repeated?
8 times
what are 3 additional pathways?
1) unsaturated fatty acids
- already partially oxidised
- yields less FADH2
2) odd-chain fatty acids
- yields propionyl CoA in last step
- converted to succinylcholine CoA
- enters TCA cycle directly
3) branched chain fatty acids
- C1 carbon oxidised to CO2
- acetyl and propionyl CoA released in equal numbers
= requires several additional enzymes
describe the breakdown of glycerol?
1) Activated to glycerol-3-phosphate by glycerol kinase
- present in liver and kidney but absent from adipose tissue, skeletal and heart muscle
2) Dehydrogenated to dihydroxyacetone phosphate
- normal intermediate of carbohydrate metabolism
where are ketone bodies formed?
in liver mitochondria
from acetyl CoA from B oxidation
where do ketone bodies diffuse into?
into blood stream and to peripheral tissues
why are ketone bodies important?
important molecules of energy metabolism for heart muscles and renal cortex
- converted back to acetyl CoA which enters TCA cycle
what happens normally in ketosis?
fatty acid oxidation yields acetyl-CoA
enters citrate cycle if fat and carbohydrate degradation are balanced
depends on oxaloacetate (C4 compound) for formation of citrate
oxaloacetate can be provided as a side-product of glycolysis
what happens in ketosis in starvation and diabetes?
- oxaloacetate is consumed for gluconeogenesis
- fatty acids are oxidised to provide energy
- acetyl-CoA is converted to ketone bodies
- high levels of ketone bodies in blood, too much for extrahepatic tissue (i.e. heart, brain, etc.) as ketone bodies are moderate acids
and so accumulation leads to severe acidosis (blood can’t buffer any more) - impairs tissue function, particularly central nervous system
- smell of acetone can be detected in breath
LECTURE 3 - LIPID ANABOLISM
LECURE 3 - LIPID ANABOLISM
what is lipogenesis?
fatty acid synthesis
where does de novo synthesis of fatty acids occur?
mainly in liver, kidney, mammary glands, adipose tissue and brain
when does de novo synthesis of fatty acids mainly take place?
during excess energy intake
what happens when excesss carbohydrate is taken in?
- conversion to fatty acids and triglycerides ini liver
- free fatty acids are transported in plasma bound to albumin
- triglycerides formed in liver are transported ti adipose tissue by VLDL for storage
Is lipogenesis reductive or oxidative?
reductive process
- energetically unfavourable s electrons are required
what is the pathway for lipogenesis?
Dietary starch Glucose Pyruvate Acetly CoA Fatty acids = triglycerides
- acetyl CoA is converted to fatty acids by FA synthesis and B-oxidation (lipolysis)
where does the synthesis of fatty acids from acetyl CoA occur?
occurs in cytoplasm of liver cells.
where is acetyl CoA generated?
in mitochondria
- by pyruvate dehydrogenase co[lex
is the mitochondria membrane permeable to acetyl CoA?
True or false?
FALSLE
IMPERMEABLE
what does citrate transport?
acetyl groups into the cytoplasm
how is citrate formed?
What happens with citrate is present at high concentrations?
by condensation of acetyl CoA with oxaloacetate (first step in TCA)
- citrate is transported into cytoplasm
what is the direct precursor of lipolysis?
Malonyl CoA
what is the vital first step involved in lipolysis?
- activation of acetyl CoA to malonyl CoA by acetyl CoA carboxylase
where is acetyl CoA carboxylase mainly expressed?
in liver and adipose issue
wha is acetyl CoA carboxylase essentially?
essentially a regulatory enzyme
what does malonyl CoA donate to new lipids?
carbon atoms
what does fatty acid synthase do?
catalyses synthesis of saturated long chain fatty acids from malonyl CoA, acetyl CoA and NADPH
is fatty acid synthase a single or multi enzyme complex?
MULTI-enzyme complex
- exists as a single polypeptide chain with 7 distinct enzyme activities
what are the 4 steps involved in fatty acid synthesis when using the enzyme fatty acid synthase?
1) condensation
2) reduction
3) dehydration
4) reduction and release
what is the name of the protein that fatty acid synthase contains?
acyl carrier protein (ACP)
are fatty acids synthesised in a single reaction or a cycle of reactions?
in a cycle of reactions
if you use acetyl CoA and malonyl CoA as precursor, what does one cycle of reactions add to the growing acyl chain?
adds 2 carbons
- derived from malonyl- CoA
- growing acyl chain is attached to ACP
- requires NADPH as electron donor
what length does the chain of carbons need to be in order for the fatty acid to be released?
needs to be C-16
e.g. palmatic acid (C16) is the longest fattty acid created by fatty acid synthase
what is required to elongate the chain further or add unsaturated bonds?
further enzymes
when is synthesises of fatty acid maximal?
when carbohydrates and energy are plentiful, and when fatty acids are scarce
what has an essential role in regulating fatty and synthesis and degranulation?
acetyl CoA carboxylase
what signals the fed state in acetyl CoA carboxylase regulation?
insulin
= stimulates storage of fuels and synthesis of proteins
what signals the starved state?
what signals the requirement for energy?
starved - glucagon
- epinephrine signals requirement for energy
= mobilse glycogen stores
what stimulates allosterically in acetyl CoA carboxylase regulation?
citrate
when are citrate levels high?
high when acetyl CoA and ATP are abundant
what is acetyl CoA carboxylase regulation antagonised by?
palmitoyl CoA
when is palmitoyl CoA abundant?
when fatty acids are in excess
what does the synthesises of triglycerides require?
glycerol-3-phosphate(G3P)
what produces G3P from GLYCEROL?
liver
what produces G3P from GLUCOSE?
adipose tissue
when does adipose tissues only produce triglycerides?
only during the fed state
- insulin stimulates adipose tissue uptake of glucose
what does triglyceride formation involve?
esterification
what other 3 things does the liver also synthesise?
(i) phospholipids
(ii) cholesterol
(iii) lipoproteins
AMINO ACID CATABOLISM
AMINO ACID CATABOLISM A
when amino acids are not used as building blocks, what happens to them?
they are degraded
= no storage for amino acids
what is the main site for amino acid degradation?
liver
what produces single amino acids and di and tai-peptides?
proteolytic enzymes in stomach and intestine
what happens to the single amino acids and di tri-peptides?
= absorbed into intestinal cells and released into blood for absorption by other tissue
describe protein turnover.
- tightly regulated
- takes place at different rates
- damaged proteins have to be removed
what do some amino acids also contain in the side chain?
nitrogen
what does amino acid breakdown produce?
ammonia (NH3) & ammonium ions (NH4+)
Yes or NO.
Is NH4+ toxic at high concentration?
Yes
- build up leads to severe problems
what are 4 major nitrogen containing excretory molecules?
1) Urea 80% 2) uric acid 3) creatinine 4) ammonium ion (NH4+)
where is urea formed?
in liver NOT kidneys
what are the 3 steps involved in synthesises of urea?
1) transamination
= transfers an amino group to a ketoacid to form new amino acids.
2) de-amination
= removal of an amine group from a molecule of amino acid to eventually form ammonia
(( = converting nitrogen to ammonia ))
3) urea/ornithine cycle
= biochemical reactions that produces urea (NH2)2CO from ammonia (NH3).
what moves the amino group from alpha amino acids to alpha keto acids in transamination?
amino-transferases
what is a common alpha kept acid?
alpha-ketogluterate, a TCA intermediate
= give glutamate
occurs in all tissues
in order for it to be transported to liver, what happens to the amino group of glutamate?
= transferred to pyruvate, giving alanine.
OR
= glutamin synthase adds NH4+ to glutamate giving glutamine
what are 2 major carriers of nitrogen in blood to liver?
1) alanine
2) glutamine
where does de-amiantion/urea cycle occur?
in liver
what happens in the de-amminatiton / urea cycle?
= amino group of glutamate is converted to free ammonium ion.
what are 3 examples of complex reactions that synthesises urea?
1) urea/ornithine cycle
2) 1 nitrogen from free ammonium, other form aspartic acid
3) carbon from CO2
describe the equation in which urea is synthesised?
CO2 + NH4+ + 3ATP + aspirate + 2H20
INTO
Urea + 2ADP + 2PI + AMP + PPi + fumerate
what is an intermediate in the citrate cycle?
fumarate
what happens after removal of alpha amino group?
= the remaining carbon skeletons are converted into major metabolic intermediates
= can be converted to glucose or oxidised in TCA cycle
what are 2 examples of family of amino acids that will eventually break down and describe each?
1) ketogenic amino acids
- degraded to acetyl CoA or acetoaceyl CoA
- can give rise to ketone bodies or fatty acids
2) glycogenic amino acids
- degraded to pyruvate or TCA cycle intermediates
- can be converted into phosphoenolpyruvate and then into glucose
what are 3 examples of inherited disorders that arise from amino acid degradation?
1) alcaptonuria
2) maple syrup urine disease
3) phenylketonuria
what is alcaptonuria?
= degradation of phenylalanine and tyrosine is blocked
what is maple syrup urine disease?
= degradation of valine, isoleucine and leucine is blocked
- urine smells like maple syrup
- mental and physical retardation
- prevented by appropriate diet
what is phenylketonuria?
= pheynlalanine accumulates in all body fluids
- leads to severe mental retardation if untreated
- therapy = low phenylalanine diet
what 4 defects could there be in urea cycle disorders?
1) acc1umulation of urea cycle intermediates
2) glutamine levels increase in the circulation
3) alpha -ketoglurarate is no longer regenerated
4) alpha-ketoglurarate levels become too low to fix more free ammonium ion
- elevated levels of ammonia in the blood are toxic for the nervous system
how would you treat urea cycle disorders?
= treatment with low-protein diet
= drugs which remove nitrogen
- e.g. forming complexes with amino acids which are excreted
- gene therapy in hepatocytes
