Metab 1-6 Flashcards
What is energy used for in the body and where does the energy come from?
for growth, repair and activity
from diet
What is catabolism?
breaking larger molecules into smaller ones to release energy
What is anabolism?
building up molecules using energy (ATP)
What are key components of the diet?
carbohydrate, proteins, minerals & vitamins, water, fibre, fats
How is energy used up in the body?
BMR, physical activity, thermoregulation
how do you work out BMI?
weight (kg) / height ^2 (m)
What is the desirable BMI?
18.5-24.9
what is obese BMI?
> 30
Describe marasmus in terms of calorie, protein intake, oedema and appearance
deficient in calorie & protein, no oedema and appears thin, bony, emaciated
Describe kwashiorkor in terms of calorie & protein intake, oedema & appearance
low calorie intake, no protein intake, oedema (ascites), thin limbs with swollen belly
how does marasmus cause anaemia?
lack of haemoglobin (protein in RBC) due to no protein intake to build haem
How does kwashiokor cause ascites?
no protein synthesised in the liver, reduction in oncotic pressure, so there is no proteins to drive the fluids back into capillaries through starling’s law of capillaries causing fluid buildup
What is galactose made up of?
glucose and lactose
what are sucrose made up of?
fructose and glucose
What are the main things that happens to the carbons in glycolysis?
glucose (c6) turns into C3 (pyruvate)
what are the rate limiting steps in glycolysis?
1,3,10
What are the enzymes involved in the rate limiting steps of glycolysis?
1: hexokinase (cells), glucokinase (liver)
3: phosphofructose kinase (PKF)
10: pyruvate kinase
What controls glycolysis?
allosteric regulation
hexokinase inhibited by Glucose 6P
PFK inhibited by ATP, H+, citrate, activated by AMP, G6P
pyruvate kinase: activated by high insulin:glucagon (ratio)
Product inhibition by NAD+:NADH (lots of NADH inhibits)
what are the products of glycolysis?
net gain of 2 ATP
no loss of CO2
production of 2 NADH
what are important intermediates of glycolysis?
DHAP for synthesis of TAGs in liver & adipose for storage
1,3-BPG –> 2,3-BPG (regulates haemoglobin O2 affinity - 1,3, R state, 2,3, T state)
Pentose phosphate pathway
What does pentose phosphate pathway produce? (main function)
C5 ribose sugar for synthesis of nucleotides (e.g. DNA, RNA)
What is the importance of Pentose PP?
converts NADP+ –> NADPH
important reducing power and prevents disulphide bonds forming
(maintains free thoil (-SH) groups so that they don’t form disulphide bonds leading to proteins aggregating of haem of haemoglobin leading to formation of heinz bodies, or cataracts in lens of eyes
What is the enzyme used in pentose phosphate pathway?
glucose 5 phosphate dehydrogenase
how do disulphide bonds form? how do NADPH help?
absence of NADPH, presence of NADP+
NADPH keeps proteins in their reduced forms, preventing cataracts in eyes or heinz bodies in RBCs
When does anaerobic respiration occur?
oxygen not available and need a way of freeing up NAD+ (for step 6 of glycolysis)
What happens in anaerobic respiration?
pyruvate gets converted to lactate using lactate dehydrogenase
What happens to the lactate released in anaerobic respiration?
taken to liver or heart (good supply of O2) where the lactate is converted back into pyruvate (also using lactate dehydrogenase) then converted back into glucose via pyruvate dehydrogenase (to oxaloacetate) then PEPCK to phosphoenolpyruvate
if not converted to glucose then pyruvate taken to krebs via pyruvate dehydrogenase to acetyl CoA
what is needed to convert 1,3 BPG into 2,3 BPG?
bisphosphoglycerate mutase
Describe fructose metabolism with all the enzymes required
fructose – (fructokinase) –> fructose-1-P
fructose-1-P –(aldolase)–> glyceraldehyde 3-P (glycolysis)
What happens when fructokinase is missing?
there will be fructose in urine (fructosuria) as it can’t be metabolised
what happens when aldolase is not present? What does it cause? how do you treat this?
accumulation of fructose-1-P as it is unable to convert into glyceraldehyde-3-P (to enter glycolysis)
buildup of fructose-1-P (in liver) is damaging to the liver
treat with removing fructose from diet
How is galactose metabolised?
galactose –(galactokinase)–> galactose-1-P
galactose-1-P + UDP-glucose –(galactose-1-P uridyl transferase)–> glucose 1-P + UDP-galactose
the reverse uses UDP-galactose 4’epimerase
What happens in (non-classical) galactosaemia?
there is a deficiency of galactokinase, so galactose is converted to galactitol using aldose reductase
this process uses up NADPH which reduces protection from ROS and increases Heinz bodies buildup & cataracts in lens of eyes
What happens in (classical) galactosaemia?
there is a deficiency of galactose-1-P uridyltransferase, so there is a buildup of galactose-1-P buildup which causes damage to liver, kidney and brain
what can glucose-1-P then turn into?
glycogen
What is the structure of glycogen?
a branched glucose polysaccharide (good for storage)
alpha 1,6, bonds branches whilst a1,4 are straight
Where is glycogen stored? what is it’s function? what happens when it is depleted?
in liver & muscles
maintains blood glucose for 2-10 hours after meals
once it is depleted, gluconeogenesis begins
Describe the process of glycogenesis
glucose –(hexokinase)–> Glucose-6P –(phosphoglucomutase)–> Glucose-1P –> UDP-glucose (like product of galactose metab.) –(glycogen synthase)–> glycogen
what is the enzyme used in glycogen synthesis and what is it activated by?
glycogen synthase activated by insulin
describe glycogenolysis
glycogen –(glycogen phosphorylase)–> glucose-1-P –(phosphoglucomutase)–> Glucose-6-P –(glucose 6 phosphatase)–> glucose
what is the enzyme used in glycogenolysis and what is it activated by?
glycogen phosphorylase activated by glucagon
where does glycogenolysis occur? why?
only possible in liver because glucose-6-phosphatase is only present in liver and NOT in muscles, which is required for G6P to go back to glucose
where does gluconeogenesis occur? when is it activated? function? possible substrates?
makes new glucose once glycogen stores depleted (after about 8 hrs fasting)
occurs in liver & kidney cortex
possible substrates: pyruvate, lactate, glycerol, glucogenic amino acid NOT acetyl CoA
why is it not possible to use acetyl CoA as a substrate for gluconeogenesis?
pyruvate dehydrogenase (step 10) is irreversible as there is a loss of carbon (CO2)
what are the enzymes used in gluconeogenesis? why?
need to bypass irreversible steps 1,3,10
10: pyruvate –(pyruvate carboxylase)–> oxaloacetate
oxaloacetate –(PEPCK)–> phosphoenolpyruvate
3: fructose-1,6-bisphosphate
1: glucose-6-phosphatase
what is gluconeogenesis stimulated and inhibited by?
glucagon and cortisol stimulate
insulin inhibits
(insulin:glucagon ratio)
What happens if there is a deficiency of glucose-6-phosphatase? (Von Gierke’s disease)
hypoglycaemia - can’t make enough glucose in the final step of gluconeogenesis
tired, lethargic, won’t thrive to grow as lack of glucose
hepatomegaly (v large store of glycogen in the liver)
where does the TCA / krebs cycle occur?
in the mitochondria
what is the TCA cycle regulated by? what is the regulatory step?
energy availability e.g. ATP:ADP ratio, NADH:NAD+ ratio
regulatory step: isocitrate dehydrogenase
activated by ADP, inhibited by ATP
what are the intermediates of the TCA cycle used for?
build fatty acids, amino acids, haem, glucose
what is the point of the ETC & ox/phos?
to release energy store in carrier molecules to make ATP
describe what happens in the ETC?
electrons from NADH & FAD2H flow down the proton carrier pumps
energy is released from each pump the e- passes through and this energy is used to push hydrogen through from the matrix to intermitochondrial space (against concentration gradient), creating a proton motive force (pmf)
when the H+ ions travel back down along conc. gradient, it passes through ATP synthase which combines ADP & Pi to form ATP
oxygen is the final carrier of the ETC
what happens to the electrons in the ETC?
NADH travels down pumps 1,3,4
FAD2H only down 2 pumps so fewer energy
the electrons combine with H+ and O2 to form water
what happens to the ox/phos when ATP is high?
ADP will be low so no substrate for ATP synthase
H+ accumulates in intermembrane space (no activation of ATP synthase as no ADP) and can’t be pump across the membrane, ETC stops
what causes inhibition of the ETC? how?
cyanide & CO - bind to haem group of the final proton complex (4), and binds to it with higher affinity than oxygen, so oxygen can’t bind to the final carrier and so neither can electrons - ETC stops
there will be obviously reduction to ATP production from ATP synthase
How does uncoupling work in ETC?
uncoupling proteins allow H+ move through membrane unregulated, to travel back into the matrix from intermembrane space without passing through ATP synthase, so there is less pmf and energy from pmf is lost as heat (instead of ATP synthesis)
what is a natural uncoupling protein and ann unnatural?
natural: thermogenin from brown adipose tissue
unnatural: DNP from slimming pill
what is a risk of uncoupling protein?
massive heat lost and people can die from hypothermia
keep burning more fat of body as ATP is not used
what are symptoms of diabetes from hyperglycaemia? name micro, macro and others
damage to blood vessels:
macro: stroke / MI , peripheral artery disease
micro: foot ulcers, nephropathy, retinopathy, neuropathy
urogenital infections (thrush)
glucosuria, polyuria, polydipsia
what are the symptoms of diabetes from inadequate metabolism?
tiredness, ketoacidosis, unexplained weight loss
what are the effects of insulin?
increase glucose uptake to tissues via GLUT4 receptors
increase glycogenesis
decrease gluconeogenesis
increase lipogenesis
increase protein synthesis
all works to store - lower plasma gluc conc
what are the effects of glucagon
increased glycogenolysis increased gluconeogenesis increase lipolysis decrease cell uptake of AA al increase plasma gluc conc - energy
what are the 2 main causes of diabetes? what does this cause?
lack of insulin production (ß-cell damage) or cells no longer sensitive to the insulin produced
cells can’t take up glucose
how do you diagnose diabetes?
2 test if asymptomatic and 1 test with symptoms
fasting glucose levels should be below 7mmol
oral glucose tolerance test - no higher than 11.1mmol
HbA1c lower than 6.5% (5% normal person)
why are diabetics at high risk of urogenital infections?
there is glucose in urine which bacteria can eat off
glucose stays in kidney tubules because there is so much glucose that the kidney can’t take it all back in
why is HbA1c a good indicator of diabetes management?
A1c in haemoglobin is glycosylated when there is a high plasma conc of glucose
as haemoglobin survives for 120 days, it shows the results from the past 3 months
initial treatment for diabetes? if it doesn’t work?
initially: low glucose diet, exercise
then metformin
insulin eventually
describe type 1 diabetes
normally diagnosed at a young age
autoimmune destruction of ß-cells on islet of Langerhan of pancreas
genetic predisposition
typically lean people
require insulin injections
rapid progression - can go into ketoacidosis if not treated
weight loss, polyuria, polydipsia
describe type 2 diabetes
normally diagnosed when adults
cells become resistant to insulin production (too much high circulation glucose so tachyphylaxis to insulin)
mostly lifestyle related
often overweight
manage with diet & exercise, bariatric surgery, metformin
What are dietary proteins broken down by?
peptidases and proteases in GIT to release AA
what are the 8 essential amino acids?
isoleucine, leucine, threonine, histidine, lysine, methionine, phenylalanine, tryptophan, valine
what happens to proteins during starvation and what is it mediated by?
breakdown of protein stores mediated by cortisol
in amino acid breakdown, what is the first step? what are the processes involved? what is it converted to?
-NH2 is removed, by transamination or deamination
converted to urea and excreted in urine
what happens to the carbon skeleton part of amino acid that’s left over?
converted into several different compounds that feed into other metabolic pathways
