Basics of metabolism + balancing act SDL

Define metabolism

• the overall process through which living organisms acquire and use free energy to carry out various functions

what are the 2 categories of metabolic processes

1. catabolic

2. anabolic

what are metabolic pathways

• a series of connected enzymatic reactions that produce specific products

what catalyses metabolic pathways?

• enzymes

what helps reduce the formation of useless/toxic by-products of metabolic reactions?

• high specificity of enzymes, ensuring efficiency of reactions

what are 6 categories of enzyme reactions?

• oxidation-reduction

• transfer of chemical groups

• hydrolysis

• removal of chemical groups

• linking two groups together

• isomerisation

how are enzymes regulated in metabolic pathways?

• by monitoring the effects that the changes in enzyme activity has on the whole metabolic pathway.

what are the 2 levels of control of metabolism?

• intrinsic

• extrinsic

what is involved in intrinsic regulation of metabolic pathways

• feed forward and feedback mechanisms - self regulation in response to change in levels of substrate or products

what is involved in extrinsic control of metabolism

• a cell in a multicellular organism changing its metabolism in response to signals from other cells

define catabolism

• the breakdown of large organic molecules into smaller molecules, releasing energy contained in the chemical bonds

what is energy

• the capacity for doing work

how do we measure energy in terms of metabolism

• the capacity to produce heat

what are the 3 steps in aerobic respiration

1. glycolysis

2. kreb’s cycle

3. oxidative phosphorylation

what is the function of the kreb’s cycle?

• release of stored energy throguh oxidation of acetyl-CoA into ATP, NADH, FADH2 and CO2

what is the function of oxidative phosphorylation

• ATP is produced due to transfer of electrons from NADH and FADH2 to O2 via electron carriers, generating a proton gradient, which then provides the energy for ATP synthase.

how many steps are there in the kreb’s cycle?

• 8

how many enzymes are involved in the krebs cycle?

• 8

what does each cycle of the krebs cycle regenerate?

• oxaloacetate and 2 Co2 molecules

what is substrate level phosphorylation

• when energy is released from substrates which directly transfers a PO4^3- molecule to ADP, generating ATP

what is the difference between oxidative and substrate-level phosphorylation

• substrate levels involves the direct transfer of a phosphate to ADP from a substrate

• oxidative involves the generation of a proton gradient and the action of ATP synthase

what are the 3 VFAs produced by ruminants?

• acetate

• propionate

• butyrate

what happens to most of butyrate once absorbed?

• converted into ketone bodies or CO2

where is acetate principally used in ruminants (with some species differences)?

• peripheral tissues - fat and muscle especially

what happens to propionate once absorbed by ruminants?

• largely converted into glucose - 50-60% of the animals glucose.

what are the steps of propionate conversion into glucose?

• propionyl CoA → methylmalonyl CoA → succinyl CoA → kreb’s cycle

what vitamins are essential for propionate conversion into succinyl-CoA?

• biotin (vitamin H)

• vitamin B12

how can propionate be used directly for glucose generation?

• it interrupts krebs cycle at the point of pyruvate.

• with the correct enzymes and substrates present, pyruvate leaves mitochondria for cytosol and is converted back to glucose for export

propionate can be converted to succinyl CoA to enter the krebs cycle, what else can it be converted into?

• directly into glucose

• oxaloacetate

what is the BER/BMR?

• basal energy requirement, or basal metabolic rate

what does the BER/BMR represent?

• the amount of energy needed to maintain life

how do we express BER/BMR?

• kcal/day for smallies

• MJ in large animals

what do RMR or RER stand for?

• resting metabolic rate

• resting energy requirement

why do we use RMR/RER more in vet medicine than BER/BMR?

• it represents the energy needed for the animal when ‘rested’ but also includes body size, age, sex, species and other life-stage factors.

• it’s proportional to metabolically active tissue and lean body mass

what calculation do we use for RMR/RER for animals weighing 2-30kg?

• (30 x body weight in kg) + 70

what calculation do we use for RMR/RER for animals weighing <2 and >30kg?

• 70 x (bodyweight in kg)^0.75

what is the relationship between size and energy requirement based on?

• interaction between animal’s weight and surface area as energy is lost constantly thorugh skin

why do the RMR/RER need to be adjusted for birds/reptiles?

• because they have higher metabolic rates and are linked to the environment (ectotherms)

what additional factor do we need to use for the calculation of RMR/RER for birds and reptiles?

• K factor

what is MER?

• maintenance energy requriement

how do we calculat MER?

• RER + energy needed for exercise, digestion + food absorption

  • it’s the same equation as RER

how can we adapt our RER/MER for sick/injured animals?

• we can use illness factors to predict the requirements in these conditions

• but avoid over feeding and use more conservative energy estimates

what do we call the RER when it’s adjusted for individual parameters?

• daily energy requirement - DER

• daily energy expenditure - DEE

what do we mulitply our RER by for a) dogs b)cats that are: critical care/hospitalised

• by 1

what do we mulitply our RER by for a) dogs b)cats that are: weight/loss or obese

• dogs - 1 x

• cats - 0.8-1.0 times

what do we mulitply our RER by for a) dogs b)cats that are: overweight prone/inactive

• dogs - 1.2-1.4 x RER

• cats - 1.0 x RER

what do we mulitply our RER by for a) dogs b)cats that are: neutered adults

dogs - 1.6 x RER

cats - 1.2 x RER

what do we mulitply our RER by for a) dogs b)cats that are: intact adult

dogs - 1.8 x RER

cats - 1.4 X

what do we mulitply our RER by for a) dogs b)cats that are: gestating

dogs - 1.6 - 2.0 X (dogs remain stable until third trimester when E req increases)

cats - 2-3 x (cats need increases steadily though gestation)

what do we mulitply our RER by for a) dogs b)cats that are: lactating

dog - 2-6 x RER

cat - 2-6 x RER

what do we mulitply our RER by for a) dogs b)cats that are: juvenile growing <4 mo

dog - 2-3 X

cat - 2-3 X

what do we mulitply our RER by for a) dogs b)cats that are: juvenile growth >80% adult weight

dog - 1.8-2.0 X

cat - 2.5 X

how many MJ is 500 kcal?

• 2MJ

what is metabolic homeostasis

• the balance between need and availability of ATP

how is intertissue integration thtat’s required for metabolic homeostasis achieved?

1. concentration of nutrients or metabolites in blood affects the rate they’re used

2. hormones carry messages to individual tissue about physiological state and nutrient supply/demand

3. CNS uses neural signals to control tissue metabolism - directly/via hormones

what type of hormone is insulin?

• anabolic

what type of hormone in glucagon?

• catabolic

what protein does insulin promote the production of in the liver?

• albumin

when do the lowest levels of glucagon occur?

• after a high carbohyrate meal

what hormones and neurotransmitters are insulin counterregulatory hormones

• adrenaline

• noradrenaline

• cortisol

how is the release of cortisol, adrenaline and noradrenaline mediated?

neuronal signals

what metabolic condition triggers the release of cortisol, adrenaline and noradrenaline?

• hypoglycaemia

how does the release of insulin counterregulatory hormones occur?

• ACTH is released from the pituitary and stimulates release of cortisol from adrenal cortex

• detection of low blood glucose by hypothalamic regulatory centre stimulates the release of adrenaline from the adrenal medulla and noradrenaline from nerve endings

how does stress impact the pancreas?

• adrenaline promotes glucagon release

how does stress impact hepatocytes?

• directly promotes the binding of glucagon to liver cells

• via different mechanisms to promote glycogenolysis and gluconeogenesis inside hepatocytes

how does stress impact muscles

• adrenaline binds to receptors resulting in glycogenolysis

how does stress impact adipose cells

• adrenaline acts and stimulates hormone-sensitive lipase → fatty acid mobilisation

what is reciprocal regulation?

• when the same molecule has opposing affects on catabolic and anabolic pathways

  • different enzymes have opposite responses to the same metabolic signal

what does reciprocal regulation prevent?

• unnecessary breakdown or storage where anabolic and catabolic pathways occur in the same cellular location

what are the 2 enzymes that govern glycogen?

• glycogen synthase

• glycogen phosphorylase

how is reciprocal regulation relevant in termss of glycogen storage?

• adrenaline and glucagon promote glycogen phosphorylase and inhibit glycogen synthase

• insuin promotes glycogen synthase but inhibits glycogen phosphorylase

what are the 3 metabolic pathways affected by insulin?

1. glycogenesis

2. lipogenesis after high carb meal

3. amino acid uptake and protein snythesis

what 2 metabolic pathways are affected by glucagon

• gluconeogenesis

• fatty acid release from adipose tissue

what 2 metabolic pathways are affected by adrenaline

• glycogenolysis from muscle and liver

• lipolysis

what 3 metabolic pathways does cortisol affect in this context

1. amino acid mobilisation from muscle protein

2. gluconeogenesis

3. fatty acid release from adipose tissue