Metabolic Pathways Flashcards
what is glycogenesis
synthesis of glycogen from glucose
what is glycogenolysis
breakdown of glycogen to from glucose
what is glycogen
major storage molecule of glucose
where is glycogen stored
in the liver and in muscle
what is the role of liver glycogen
broken down into individual glucose molecules which are released into bloodstream to supply other organs with energy inbetween meal times
what is the role of muscle glycogen
can only be used by muscles, not available for maintenance of blood glucose levels.
provides energy via glycolysis and the TCA during bursts of physical activity
what causes glycogenolysis to fluctuate
meal times
what is the primary source of glucose overnight when hepatic glycogen is depleted
gluconeogenesis
what accounts for the majority of glucose in blood after meals
dietary carbohydrates
what is glycogen made of
polymer of glucose molecules
how are the glucose molecules in glycogen bonded
alpha 1-4 glycosidic links (between carbons 1 and 4)
how are branches introduced into a glycogen molecule
via an alpha 1-6 glycosidic chain
what reaction facillitates glycogenolysis
phosporolysis
how is glucose added to glycogen
can only be added to existing glycogen chain ( a glycogen primer of glycogenin protein with at least four glucoses attached)
how is glucose trapped inside a cell
is phosphorylated to form glucose-6-phosphate
what happens to glucose 6 phosphate when energy s recquired
glycolysis
what happens to glucose 6 phosphate when there is no need for energy
converted to glycogen
describe how glucose 6 phosphate is activated
glucose 6 phosphate -> glucose 1 phosphate (phosphate group moved from carbon 6 to 1), UDP- glucose
how is UDP- glucose added to glycogen
covalently bonds, UDP left over is phosphorlyated into UTP.
process uses 1 ATP
what are the functional groups of UDP-glucose
nucleotide like ATP:
uracil base, ribose sugar, two phosphate groups, attached to second phosphate group is glucose
what are simple precursors converted to
activated intermediates
what is the activated forms of phosphate and glucose
ATP
acetyle- CoA
what is glucose synthase
synthesises glucose from UDP glucose- cannot start new chain or introduce branchd
what is the rate limiting enzyme of glycogenesis
glycogen synthase
what is the branching enzyme of glycogen
transglyosylase
what catalyses glycogenolysis
glycogen phosphorylase
what is the rate limiting step of glycogenolysis
when glucose group cleaved from glycogen and adds a phosphate group to it so the product is glucose-1-phosphate
catalysed by glycogen phosphorylase
what is glycogenolysis
when glucose removed from its stored form of glycogen
where can glucose be de phosphorlyated
in liver NOT skeletal muscle
briefly list the steps of glycogenolysis
glycogen-> glucose 1 phosphate-> glucose 6 phosphate -> either:
-glycolysis if energy needed or (in liver only) deposphorlyated -> glucose released into blood via GLUT2 transporter
what regulates both glycogenesis and glycogenolysis
hormomes
what stimulates the synthesis of glycogen and how
insulin- signals availability of carbs in the bloodstream, stimulates the synthesis of glyocgen
what inhibits the synthesis of glycogen
glucagon- hormone of starving state, stimulates the breakdown of glycogen and glycogen phosphorylase,
what stimulates the breakdown of glycogen and how
glucagon, adrenaline and cortisol- allow rapid mobilisation of glycogen stores,stimulate glycogen phosphorylase
what inhibits the breakdown of glycogen
insulin
what are glycogen storage diseases and what causes them
group of disease with increased glycogen deposits in liver or muscle or both
what is glycolysis
the breakdown of glucose by enzymes releasing energy and pyruvic acid
what are the three phases of glycolysis
stage 1 - glucose is trapped and destabilised
stage 2 - two interconvertible three carbon molecules are formed
stage 3 generation of ATP
what is the overall reaction of glycolysis
glucose + 2 ADP + 2 Pi + 2 (NAD+)
->
2 pyruvate + 4 ATP + 2 H2O + 2 NADH + 2 (H+)
describe the process of glycolysis
glucose – (2 ATP -> 2 ADP) –> fructose- 1, 6- bisphosphate –> 2 triose phosphates – ( 4 ADP -> 4ATP) (2 NAD+ -> 2NADH + 2H+) –> 2 pyruvate
what is the cellular need for glycolysis
production of ATP, provision of building blocks for synthetic reactions
how is glycolysis controlled
enzymes catalysing irreversible reactions
- hexokinase: substrate entry
- phosphofructokinase: rate of flow
- pyruvate kinase- product exit
what is the fates of the products of glycolysis
4 ATP = energy
2 pyruvate = carbon to fuel TCA in mitochondria
2 NADH +2H+ = electron transport chain and ATP synthesis
what is glucogenesis
source for new glucose when glycogen stores are delpeted – generates new glucose from non carbohydrate pre cursor molecules, occurs during prolonged starvation when no dietary carbs or glycogen stores depleted
what are the three precursors for glucose in gluconeogensis
lactate (lactic acid), amino acids, glycerol
why is pyruvate converted to lactic acid
during anaerobic resp to convert NAD+ to NADH
where is lactate synthesised
in skeletal muscle during anaerobic synthesis
where are amino acids derived from
muscle protein by proteolysis
where is glycerol derived from
from triglycerides by lipolysis in adipose tissue
does gluconeogenesis require or release energy
very energy expensive
where does gluconeogenesis happen
mainly in the liver, small amounts in the kidney
what is gluconeogenesis is relation to glycolysis
the reverse
what allows gluconeogenesis to be the reverse of glycolysis as this has irreversible reactions
special enzymes that are able to bypass the irreversible reactions
what does gluconeogensis proceed via
the synthesis of oxaloacetate in the mitochondria
can all amino acids be precursors for gluconeogenesis
no but majority can be
what is oxaloacetate
immediate in the TCA cycle that accepts acetyl groups, can be synthesised from pryuvate
how many pyruvates are needed to make a glucose
2 as pyruvate 3 carbon molecule, glucose 6 carbon molecule
how much ebergy is needed to make one molcule of glucose in gluconeogensis
equivalent of 6 ATP (4 ATP and 2 GTP)
how much energy does glycolysis produce from every glcose oxidised
2 ATP
what is lactate a precursor of
gluconeogenesis
where is lactate generated
in muscles under anaerobic conditions
how does lactate reach the liver
carried in the blood stream- is a polar molecule
what happens to lactate when it reaches the liver
enzymes covert it to pyruvate and the glucose using 6 atp
why is gluconeogenesis in the liver important
Means neither liver or bloodtsream acidifies too much, takes metabolic burden way from the muscle
how are amino acids grouped
either
- ketogenic (cannot be used for making glucose)
- glucogenic (can be used as precursors for gluconeogensis)
how can glucogenic amino acids enter the TCA cycle
either as amino acids or be converted into pyruvate
what can any molecule that can be converted to pyruvate also be converted to
oxaloacetate
how can ketogenic amino acids enter the tca cycle
converted into acetyl CoAor acetyoacetyl CoA and can enter only if oxaloacetate present to accept it
at which two levels is glycolysis and gluconeogenesis regulated
system level: hormones
individual cells level: allosteric effectors
which hormones regulate gluconeogenesis and how
, glycagon signals a need for glucose therefore stimulates gluconeogenesis and inhibits glycolysis.
Insulin signals availability of glucose so inhibits gluconeogenesis and stimulates glycolysis
what allosteric effectors regulate gluconeogenesis and how
amp/ adp signal the requirement for energy, stimulate glycolysis and inhibit glucneogeneis as energetically expensive
ATP singals high availbality of energy inhibits glycolysis and stimulates gluconeogenesis
Fructose 2,6-bisphosphate is a intermediate of glycolysis that is in high con in fed state and low con in starved state. Stimulates glycolysis in high conc and inhibit glucneogensis
what are citrate, alanine and acetyl-CoA
important pre cursor molecules for biosynthetic processes, all present at high conc when intermediates for building blocks for biosynthetic processes are abundant, high conc stimulate glucoenogensis and inhibit glycolysis
what is fat intake and deposit of fat associated with
human disease
what does increase fat intake without appropriate energy expenditure lead to
increase in numbers of adipocytes, more fat deposits in adipocytes (obesity)
what does the control of energy balamce depend on
genetically linked factors (protein messengers regulating appetite)
environmental factors (food abundance and fashionable food)
why is fat required
energy source,
for essential fatty acids (required but cannot be synthesised-polyunsaturated),
fat soluble vitamins (A, D, E & K- stored in and up-taken in fat)
what can deficiencies in essential fatty acids lead to
membrane disorders:
increased skin permeability, mitochondrial damage- reduction in energy generation
give examples of simple lipids
fatty acids, triglycerides, waxes (protective fats on animal hair)
give examples of compound lipids
fats associated with other compound groups
phospho-, glyco- lipids, lipoprotein
steroids
cholesterol, steroid hormones
name the different types of lipid
simple, compound and steroid
describe the structure lipids
predominantly hydrocarbon (hydrophobic), usually contain long chain fatty acids, insoluble in water
what is the main energy storage form in adipose tissue
triglycerides
what are triacylglycerols
triglycerides
what is the main source of energy in our diet
triglycerides
how are triglycerides stored
compact as dont need concomitant storage of water as hydrophobic- high energy yield per gram
what is the structure of triglycerides
glycerol and three fatty acids
each of the three hydroxyl groups of the glycerol is esterified with the carboxyl of the fatty acid to make a triacylgylcerol
what is the structure of fatty acids
long, straight chain hydrocarbon with a carboxly (acid) group at one end
aliphatic (no rings)
usually contain an even number of carbon atoms
what are the types of fatty acid
saturated (no double bonds)
unsaturated (1 double bond)
polyunsaturated (several double bonds)
what configuration are double bonds in in fatty acids
usually cis (within the same plane) not trans (opposing sides)
what is the most common fatty acid in humans
plamitic
what does the number 16:0 mean in palmitic acid
number of carbons: number of double bonds
what are the numbers for stearic and oleic acis
stearic 18:0
oleic 18:1
describe the prevalence of polyunsaturated fatty acids and give an example
Occur only in small amounts
many can not be synthesised by the body
essential fatty acids
e.g. linoleic acid (18 : 2):
what is the limit for the body making double bonds
9 carbons away from the carboxyl group- past this cant make double bond (further than 9= essential fatty acid)
what are the two ways of naming the carbons in fatty acids
Either: carboxyl group is C-1
Or:
C adjacent to carboxyl group is alpha carbon
C furthest away is omega carbon
(omega 3 fatty acid- double bond away from omega carbon)
what short do fatty acids have to be to be liquid at room temp
8 or less
what does the presence of double bonds do to the melting point
reduce it dramatically
what is the difference between plant and animal fats
plant= large proportions of unsaturated fatty acids- liquid
animals= mostly palmitic and stearic acid- solid
what are the main products of fat digestion
glycerol, fatty acids, monoglycerides (glycerol molecule with fatty acid still attached)
where is glycerol absorbed
in intestinal epithelial cells
where are the products of fat digestion absorbed
into epithelial cells lining the intestine (mucosal cells)
what fatty acids can enter the portal blood directly
short and medium length ones
what has to happen to longer chain fatty acids and monoglycerides so they can be absorbed
are re-synthesised to triglycerides
what are chylomicrons
type of lipo protein that is transportable in the blood stream-made of newly absorbed triglycerides that have been coated with protein, phosholipids and cholesterol
where do chylomicrons go after they are formed in mucosal cells
Enter lymph, then the blood stream
At muscle and adipose tissue, chylomicrons are attacked and cleaved by lipoprotein lipases
(way of transporting fat to any tissue that need it)
what happens when chylomicrons are cleaved at muscle and adipose tissue
fatty acids left are
- resynthesised into triacylglycerols (in adipose tissue, for storage)
- oxidised to provide energy (in muscle)
(depends on amount of FA available)
what is the breakdown of lipids cause and caused by
lipolysis
hormone sensitive lipases
when does lipolysis of stored fat occur and what happen
when energy is needed, releases free fatty acids and glycerol
what regulates hormone sensitive lipases
hormones e.g. adrenaline sensitive is inhibited by adrenaline
what do fatty acids have to converted to before they can be oxidised to make energy, how does this happen
CoA derivatives (activated)- this is done by linking the acid to CoA which happens in the cytoplasm and requires equivalent of 2 ATP= making acyl- CoA
why and how does acyl-CoA need to be transported to the mitochondrial matrix
for further oxidation of the fatty acids
transported there by special carrier mechanism called the carnitine shuttle (as acyl-carnitine)
net result acyl-CoA located in mitochondrial matrix
what is beta oxidation
a series of reactions that happen in the mitochondrial matrix and produces:
1 acetyl-CoA
1 FADH2
1 NADH + H+
1 fatty acyl-CoA, shortened by 2 carbon atoms
why is the beta oxidation reaction repeated 8 times
to increased yield for:
- FADH2, NADH and H+ used for ATP generation in oxidative phosphorylation
- acetyl-CoA oxidised in TCA cycle to CO2
what is the P/O ratio
amount of ATP that can be generated for the reduction of a single oxygen to water (for complete oxidation of stearic acid 120 ATP compared to glucose 30 ATP)
what do additional pathways require
additional enzymes
what happens to the glycerol in the break down of fatty acids
is phosphorylated and activated to glycerol 3 phosphate and enters mainstream metabolism as can be converted to substrate for glycolysis- can present in liver and kidney but absent from adipose tissue, skeletal and heart muscle
describe ketone bodies
Formed in liver mitochondria
from acetyl-CoA from b oxidation
contain ketone groups (hyrdophillic)
Diffuse into the blood stream and to peripheral tissues
Important molecules of energy metabolism for heart muscle and renal cortex
converted back to acetyl-CoA, which enters TCA cycle
why cam ketosis cause problems in starvation or diabetes
oxaloacetate is consumed for gluconeogenesis
fatty acids are oxidised to provide energy
acetyl-CoA is converted to ketone bodies
high levels in blood
too much for extrahepatic tissue (i.e. heart, brain, etc.)
ketone bodies are moderate acids
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
