changes to metabolism Flashcards
describe the fuel storage capacity for the body for a 70kg man
For a 70kg man:
Glycogen= 0.2kg= 800kcal
Triacylglycerol=15kg=135,000 kcal
Protein=6kg=24,000 kcal
how many amino acids are there
20
essential and non essential
what are essential amino acids
cannot be produced by the body
Arginine
Histidine
Methionine
Threonine
Valine
Leucine
Lysine
Isoleucine
Phenylalanine
Tryptophan
what are non essential amino acids
Can be produced by the body
Alanine
Asparagine
Aspartate
Cysteine
Glutamate
Glutamine
Glycine
Proline
Serine
Tyrosine
what 3 categories can essential amino acids be divided into
- glucogenic:
Arginine
Histidine
Methionine
Threonine
Valine
- ketogenic
Leucine
Lysine
- glucogenic + ketogenic
Isoleucine
Phenylalanine
Tryptophan
what 2 groups can non essential amino acids be divided into
- glucogenic
Alanine
Asparagine
Aspartate
Cysteine
Glutamate
Glutamine
Glycine
Proline
Serine
- glucogenic + ketogenic
Tyrosine
explain alanines conversion to pyruvate
Alanine loses its amino group by transamination to form pyruvate catalysed by alanine aminotransferase
explain asparagines conversion to oxaloacetate
Asparagine is hydrolysed by asparaginase, liberating ammonia and aspartate.
Aspartate loses its amino group by transamination via the enzyme aspartate aminotransferase to form oxaloacetate.
explain glutamines conversion to alpha-ketoglutarate
Glutamine is converted to glutamate and ammonia by the enzyme glutaminase (2).
Glutamate is converted to -ketoglutarate by oxidative deamination by glutamate dehydrogenase (1).
explain tyrosines conversion to fumarate
A multi-step reaction
Transamination
- Tyrosine –>Hydroxy-phenylpyruvate
- ⍺-ketoglutarate—> Glutamate
Dioxygenation:
- Hydroxy-phenylpyruvate—> Homogentisate
- O2 + Ascorbate (Vit. C)–> CO2 + H2O
Dioxygenation:
- Homogentisate–> 4-Maleylacoacetate
Isomerisation:
- 4-Maleylacoacetate–> 4-Furmarlacoacetate
Hydrolysis:
4-Furmarlacoacetate–> Fumarate and Acetoacetate
explain the causes of starvation
Inability to obtain food
Desire to lose weight
Clinical Situations:
- Trauma (shock)
- Burns
- Injury to face
- Tumour
explain what happens st metabolic level during starvation
Blood levels of amino acids, glucose, and triacylglycerols fall
Blood insulin levels are very low, glucagon levels are very high
Both factors trigger a period of catabolism, characterised by the degradation of:
- Glycogen –> Glucose
- Triacylglycerol –> Fatty Acids and Glycerol
- Protein –> Amino Acids
This results in an interchange of substrates between:
Liver
Adipose tissue
Skeletal Muscle
Brain
what determines the fates of the substrates interchanged during metabolic level of starvation
The fate of these substrates is determined by 2 crucial factors:
- The essential need to conserve glucose for those cells &tissues that really need it, such as red blood cells and brain.
- The need to mobilise fatty acids from adipose tissue andketone bodies from liver to supply energy to all othertissues, and for these other tissues to adapt to these non-glucose substrates.
describe the enzymatic changes in starvation
In all situations the flow of intermediates through biochemical pathways is controlled by 4 mechanisms:
- Availability of substrates
- Allosteric activation/inhibition of enzymes
- Covalent modification of enzymes
- Reciprocal Induction or repression of enzyme synthesis
explain the carbohydrate metabolism that occurs to the liver during starvation
Initially glycogen breakdown, then gluconeogenesis to meet the following objectives:
- Maintain blood glucose levels
- Sustain energy provision for the brain and other glucose requiring tissues (e.g. red blood cells).
explain increased glycogen degridation in the liver during starvation
After a meal glucose from food is the major source of blood sugar.
A few hours after a meal blood glucose levels start to decline.
Insulin levels drop, glucagon levels increase which stimulates (by cAMP cascade) glycogen breakdown in liver.
Liver glycogen stores will last for 10-18 hours of fasting.
explain liver, increased gluconeogenesis that occurs during starvation
Unique ability of liver to synthesise glucose is vital during starvation and becomes increasingly active as glycogen stores are depleted.
Carbon skeletons are derived from:
- Glycerol
- Lactate
- Amino acids
explain lipid metabolism in liver starvation
Increased fatty acid oxidation
- Oxidation of fatty acids derived from adipose tissue is the major source of energy for liver during starvation (this spares glucose)
- Increased synthesis of ketone bodies
Ability of the liver to synthesise and release ketone bodies (acetyl units) is unique.
- Synthesis is favoured when [acetyl CoA] produced via fatty acid oxidation exceeds the maximal rate of the citrate cycle.
- KBs are vital in starvation because they can be used by other tissues and cells provided they have mitochondria.
- Once the level of KBs in the blood is high enough, up to ⅔ of the brain can use them as fuel.
- Utilisation of KBs reduces the need for amino acid precursors for gluconeogenesis and this decreases protein breakdown.
explain carbohydrate metabolism of adipose tissue in starvation
In starvation, insulin levels decrease and hence glucose is not used for fatty acid synthesis (no signal).
explain lipid metabolism of adipose tissue in starvation
Increased degradation of TAGs
- decrease insulin & increase glucagon (via cAMP cascade) causes phosphorylation and activation of hormone-sensitive lipase.
Increased release of fatty acids
- Fatty acids obtained from hydrolysis of stored adipose TAGs are released into the bloodstream.
- Bound to albumin, they are transported to lots of tissues for use as a fuel.
- The glycerol that is produced as the result of complete TAG hydrolysis is used for gluconeogenesis by the liver.
explain carbohydrate metabolism in skeletal muscle in starvation
Glucose requirements of muscle are decreased during starvation due to very low insulin levels
explain lipid metabolism in skeletal muscle during starvation
During first couple of weeks of starvation, muscle uses fatty acids from adipose tissue and ketone bodies from the liver as fuels.
Beyond this time period, muscle utilises only fatty acids as a fuel.
- This spares ketone bodies for other tissues
- Helps promote greater increase [KB] in the blood so that some parts of the brain can utilise them
explain protein metabolism in skeletal muscle during starvation
During first few weeks of starvation there is a lot of muscle wastage due to protein breakdown.
Resulting amino acids are used for gluconeogenesis.
Because the brain can utilise KBs when the [KB] in the blood is high enough, there is less of a requirement for the liver to perform gluconeogenesis.
The knock-on effect of this is that further muscle protein degradation is paused as blood [glycerol] and [lactate] are sufficient to meet the gluconeogenic needs of the liver.
explain the brain in starvation
First few weeks, brain 100% dependent on glucose.
Later, as [KB] rises, can adapt to using ketone bodies for ⅔ of its caloric requirements – reducing the need for glucose consumption.
what is metabolic disease
Inborn Errors of Metabolism
Inborn Error = An inherited genetic disorder which is either:
- Autosomal recessive
- X-linked
what are metabolic diseases majorly due to
to defects in single genes that code for enzymes that facilitate conversion of various substrates into other products
The term inborn error of metabolism was coined by who
garrod in 1908
what did garrods work prefigure
the ‘one gene one enzyme hypothesis’ based on his studies on the nature and inheritance of alkaptonuria.
in most metabolic disorders problems arise due to what
arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of a reduced/nonexistant ability to synthesize essential compounds.
explain garrods hypothesis
He developed an increasing interest in chemical pathology, and investigated urine chemistry as a reflection of systemic metabolism and disease.
This research, combined with the new understanding of Mendelian inheritance, evolved from an investigation of a few families with an obscure and not very dangerous disease (alkaptonuria) to the realization that a whole territory of mysterious diseases might be understood as inherited disorders of metabolism.
Over the next decade he developed an understanding of the possible nature of inherited diseases of metabolism.
He formulated the “one gene, one enzyme” hypothesis and described the nature of recessive inheritance of most enzyme defects. In 1908, the core of this work was presented as the Croonian lectures to the Royal College of Physicians, entitled Inborn Errors of Metabolism and published the following year.
Garrod expanded his metabolic studies to cover cystinuria, pentosuria, and albinism. In 1923 he summarized these studies in an expanded edition of his best known work,
