metabolism

maintenance of a constant internal environment with dynamic equilibrium

failure of homeostasis > disease

• = hypothalmic-pituitary-adrenal axis
• hypothalamus releases CRF/CRH
• CRH/CRF acts on the ant. pituitary gland > ACTH release
• ACTH acts on zona fasiculata of adrenal gland > cortisol release and ACTH inhibits CRH/CRF release
• cortisol > inhibition of ACTH and CRH/CRF release

• RBCs
• WBCs
• kidney medulla
• lens of the eye
• CNS prefers glucose

• no loss of CO2
• glucose is oxidised to pyruvate
• net yield of 2 molecules of ATP
• 1,3 bisphosphoglycerate is used by RBCs to make 2,3 bisphosphoglycerate which is an important regulator in the oxygen affinity of haemoglobin

• converted to acetyl-CoA by pyruvate dehydrogenase
• PDH is a multi-enzyme complex
• reaction is non-reversible
• very sensitive to vitamin B deficiency
• regulated : inhibited by high ATP and NADH, activated by high ADP and insulin

• happens in the liver and kidney cortex
• formation of glucose from pyruvate, lactate and glycerol, amino acids if their metabolism included pyruvate or TCA cycle intermediates
• used after glycogen has been used to support glucose dependant tissues
• reverse glycolysis by-passing steps 3 and 10 these are also the sites of control
• - PEPCK - oxaloacetate > PEP increased by glycagon and cortisol and decreased by insulin
• - fructose-1,6-bisphosphatase - increased by glycagon and decreased by insulin

• during oxidative phosphorylation reactive molecules are produced as a by-product
• mitochondria produce super oxide radicals that give rise to reactive oxygen species
• these can be converted to H2O2 and water but some react with nitric oxide and can then cause damage to membranes
• antioxidants such as glutathione, NADPH, Vit E and C react with them and deactivate them

• we store glucose as glycogen it is stored in the liver and muscles
• we store it as diet glucose supply is intermittent
• glucose is converted to glycogen the regulating enzyme is glycogen synthase it is inhibited by glucagon and adrenaline and activated by insulin

• highly branched glucose polymer
• linked by alpha 1,4 ans alpha 1,6 bonds
• large molecule
• stored in granules
• limited storage as it is highly polar and thus attracts water

glycogenolysis

a small amount is always preserved

the control step involves glycogen phosphorylase which is activated by glucagon and adrenaline and inhibited by insulin

• taken to liver
• glycerol > glycerol kinase > TAG synthesis OR dihydroxyacetone phosphate (this enters glycolysis)

• broken down
• common key steps =
• - removal of amine group > urea > excreted
• - remaining C skeleton > pyruvate/oxaloacetate/alpha-ketoglutarate/succinate/acetyl-CoA

nitrogen can either undergo transamination - converted to other nitrogen compounds OR deamination and is removed from the body

• mainly in liver
• stimulated by cortisol
• uses transaminase /aminotransferase enzymes to convert into other nitrogen compounds
• ALT/AST are used to measure liver function

• happens in the liver and kidneys
• amino acids converted into ketoacids and ammonia

• phenylketonuria
• inherited disorder
• large amounts of phenylketones produced from phenylalanine
• phenylalanine hydroxylase enzyme is defective
• phenylalanine accumulates in tissues > inhibition of brain development
• treatment = restricted diet

• blurred vision
• tremors
• slurred speech
• coma
• death

• convert it to urea
• in liver catalysed by 5 enzymes
• the enzymes are effected by the amount of protein in the diet must reintroduce slowly

• spherical
• surface coat and hydrophobic core
• coat contains phospholipids and cholesterol and apoproteins
• core contains TAGs and cholesterol esters

• acetoacetate
• acetone
• beta-hydroxybutyrate

water soluble

acetone is volatile and can be excreted via the lungs

synthesised from acetyl CoA > hydroxy-methyl-glutaryl-CoA > ketone body

pathway activated when insulin:glucagon ratio falls otherwise cholesterol is made.

• beta-oxidation
• converted into many acetyl-CoA molecules

• in excess storage - tissue damage
• fasting hypoglycaemia
• exercise intolerance

• oxidative requires membrane bound complexes/substrate level requires soluble enzymes
• oxidative cannot occur in the absence of O2
• oxidative is a major process for ATP synthesis/ substrate level is minor

• hypertension
• diabetes
• cancers
• gall bladder disease
• heart disease
• osteoarthritis

• skeletal muscle
• heart
• liver
• CNS

• 12000KJ
• BMR + voluntary activities + diet induced thermogenesis

= 100*weight in Kg

affected by gender, environmental/body temp, endocrine status

• weight in Kg / (height in m)²

• fat
• carbohydrate
• protein
• water
• fibre
• vitamins
• minerals

A, D, E, K

K, Na, S, Mg, P, Ca

Fe, Zn, Se, Cu, Mn, F, Cr, Mo

marasmus - protein energy malnutrition > muscle wasting, emanciation, loss of fat, NO oedema, thin dry hair, diarrhoea, anaemia

kwasiorkor - protein malnutrition > anaemia, lethargy, oedema, ascities, re - feeding syndrome

matching the energy needed for endergonic reactions to the energy produced by exergonic reactions

quick releasing energy store found in muscle cells

creatine + ATP > creatine phosphate + ADP

the reaction is catalysed be creatine kinase

• central metabolism pathway for all sugars
• 10 steps
• aerobic glycolysis produces 2 molecules of pyruvate, 2ATP, 2NADH, 2H+, 2WATER
• anaerobic glycolysis produces 2 lactate and 2NAD+

1, 3, 10

• 3 is most important
• fructose-6-phosphate > fructose-1, 6-bisphosphate
• catalysed by PFK-phosphofructokinase

muscle - allosteric regulation inhibited by high ATP, stimulated by high AMP

Liver - hormonal regulation - insulin stimulates and glucagon inhibits

• not all of the glucose-phosphate made in the first step of glycolysis enters the rest of the glycolysis pathway.
• the PPP is important in RBCs, liver and adipose as it produces NADPH and ribose for the synthesis of nucleotides

glucose-6-phosphate dehydrogenase

low NADPH > disulphide bridge formation > proteins such as Hb become X-linked

in the case of Hb Heinz bodies form and haemolysis occurs

digested by lactase > galactose + glucose

galactose metabolised in liver (kidneys and GIT)

- inability to utilise galactose

kinase deficient - galactose stored in tissue and it is reduced to galacticol > depletion of NADPH > cataract and gluacoma

transferase deficient - galactose and galactose-1-phosphate accumulate > damage to liver, kidneys and brain

• fatty acids
• triacylglycerols
• phospholipids
• eicasanoids

• ketone bodies
• cholesterol
• bile acids
• bile salts

• produced in the catabolism of FAs, sugars, alcohol and certain amino acids
• it is important in lipid biosynthesis and can be converted into triacylglycerols, phospholipids, ketone bodies and cholestrol

• synthesised in the liver mitochondria from acetyl-CoA in a pathway involving hydroxy-methyl-glutaryl-CoA
• they are used to fuel the CNS during starvation but can lead to acidosis

• 2% is FAs bound non-covalently to albumin
• 98% is carried as lipoprotein particles.
• - chylomicrons - transport dietary TAGs to tissues
• - VLDLs -transport TAGs synthesised in the liver to adipose tissue for storage
• - LDLs - transport cholesterol synthesised in the liver to the tissues
• - HDLs - transport excess cholesterol to the liver to be deposited as bile salts

lipoprotein lipase is found on the inner surface of capillaries in adipose and muscle tissues. it acts on chylomicrons and VLDLs. It hydrolyses TAGs into FAs and glycerol. the FAs are then taken up by the tissue and the glycerol goes to the liver.

LCAT (lecithin cholesterol acytltransferase) stabilises the lipoprotein particle after core lipids have been removed by converting membrane lipid to core lipid

tissues get the cholesterol they need by receptor mediated endocytosis

atheroscleriosis

type 1- raised chylomicrons in fasting plasma - defective lipoprotein lipase

type 2a - raised LDLs - FAMILIAL HYPERCHOLESTEROLAEMIA - defective LDL receptor - severe link with CAD

type 2b - raised LDLs and VLDLs - severe link with CAD

type 3 - raised LDLs and chylomicron reminants - defective apoprotein - link with CAD

type 4 - raised VLDLs - link with CAD

type 5 - raised VLDLs and chylomicrons - link with CAD

• lifestyle - remove cholesterol and reduce fat in diet
• drugs = statins - reduce cholesterol synthesis by inhibiting HMG-CoA reductase or bile sequestrants - increase disposal

• occurs in the mitochondria
• requires FAD and NAD+ and oxaloacetate
• main function is to break C-C bonds in acetate and oxidise the C atoms to CO2
• other functions = intermediates used to make essential amino acids, haem, glucose and FAs. and reduces NAD+ to NADH for use in glycolysis and electron transfer (as well as FADH2)
• regulated by the NADH/NAD+ and ATP/ADP ratios
• acetyl-CoA > citrate > alpha-ketoglutarate > succinate > fumarate > malate> oxaloacetate

• replacing the TCA cycle intermediates
• can be from the break down of amino acids to give C4/5 intermediates
• main replacement = oxaloacetate replaced by the acitivity of pyruvate carboxylase

• mitochondria
• electron transport + ATP synthesis
• re-oxidises NADH and FADH2 and produces lots of ATP

• occurs in inner mitochondrial membrane
• electrons transferred through a series of carrier molecules to O2 causing a release in energy
• lots of energy is released as heat - maintaining body temp.
• 30% of the released energy is used to move H+ ions across the membrane

• membrane is impermeable to H+
• As electron transport proceeds H+ ions increase in concentration outside of the inner membrane
• the PMF is the potential difference of protons

• ATP synthase allows the H+ ions to cross back across the membrane thus using the energy from the PMF to drive ATP synthesis
• the greater the PMF the more ATP is synthesised

• regulated by the concentration of mitochondrial ATP
• When [ATP] is high ATP synthase stops
• H+ ions can't cross back
• [H+] increases outside the membrane -prevents more proton being pumped
• electron transport stops

• increase to membrane permeability to protons
• ET continues but ATP synthase is not active
• lots of heat generated
• occurs in brown adipose tissue

• UCP1 - uncoupling protein
• in response to cold NA activate lipase > release of FAs from TAGs
• FAs activate UCP1
• extra heat is generated

• communication
• control centre
• receptors
• effectors

negative feedback allows control

• function = deactivate and eliminate
• phase 1 - occurs mainly in the liver, exposing/adding reactive groups - P450 cytochrome enzymes
• phase 2 - still in liver, glucuronidation/sulphate conjugation/glutathione conjugation

• chemical messenger
• released by endocrine gland
• travels in blood stream

• PEPTIDE - insulin, glucagon, growth hormone
• GLYCOPROTEIN - LH, FSH, TSH, adrenaline
• STERIOD - (derived from cholesterol) cortisol, aldosterone, testosterone, oestrogen

• absorption of glucose, aas, and lipids from the GIT raises their blood concentration
• as blood glucose rises the endocrine pancreas releases insulin

• insulin secretion is depressed
• glucose uptake by muscle and adipose tissue is depressed
• falling blood glucose stimulates glucagon > glycogenolysis + lipolysis
• gluconeogenosis begins to increase

• insulin continues to fall
• glucagon, cortisol and growth hormone rise > ketogenesis in the liver

• 1st half - insulin/anti-insulin inc > anabolic state > preparing of stores
• 2nd half - mother switches to FAs increasing glucose availability for the child

failure to meet insulin demand = gestational diabetes

• inc. lactate
• low pyruvate > lack of gluconeogenesis > fasting hypoglycaemia
• inc acetyl-CoA with low lipoprotein > fatty liver

marathon - slow changes (insulin down, adrenaline/glucagon/cortisol up) - aerobic

sprint - anaerobic, rapid response to increased adrenaline and NA - high lactate and H+ > fatigue

• inc glucogenesis
• dec glucogenolysis
• inc glycolysis
• dec ketogenesis
• dec lipolysis
• inc aa uptake and protein synthesis
• inc glucose transfer

• inc glycogenolysis
• dec glycogenosis
• inc gluconeogenesis
• inc ketogenesis
• inc lipolysis

• pattern of symptoms in obese adults
• insulin resistance
• dyslipidaemia - high cholesterol
• impaired glucose tolerance
• hypertension

• appetite centre at base of hypothalamus
• 2 types of neurones:
• - primary - sense glucose,FAs and hormones in blood
• - secondary - co-ordinate response

• primary neurones can be excitatory or inhibitory
• excitatory neurones stimulate appetite and inhibitory release either Bendorphins (rewards) or alpha - MSH (suppresses appetite)

• ghrelin - peptide released from walls of empty stomach > stimulates appetite
• PYY - peptide released from SI wall - suppresses appetite
• leptin - released from adipocytes - suppresses appetite (deficiency > gross obesity)
• amylin - released from pancreas beta cells - suppress appetite

• base of brain below hypothalamus
• produces hormones: TSH, ACTH, LH, FSH, prolactin, growth hormone

• located on top of kidneys
• have outer cortex and inner medulla

• lipophillic steriod hormone
• transported around the body bound to plasma proteins
• important in stress and starvation
• decreases aa uptake and protein synthesis and increases proteolysis
• increases hepatic gluconeogenesis and glycogenesis
• decresases peripheral glucose uptake
• increases lipolysis

its release is controlled by the HPA axis

• low cortisol
• can be caused by destruction of cortex or problem with control
• > low BP, hyperpigmentation of the skin, tiredness, weakness

• high cortisol
• can be caused be adenoma in the pituitary gland, ectopic ACTH...
• > proximal muscle wasting, rapid weight gain, moon face, hyperglycaemia, hypertension

• neck
• lower larynx
• butterfly shape - two lobes + central isthmus
• produces T3/4 and calcitonin
• calcitonin produced in parafollicular cells, thyroxin and idothyronine produced in follicular cells

hypothalamus releases TRH > pituitary releases TSH > follicular cells release t3/4

• inc BMR
• normal growth and repair
• GI motility

cretinism

• autoimmune destruction of follicles
• treat with oral T4

• autoimmune
• antibodies stimulateproduction of T3/4
• treat with carbamizide

• weakness
• bradycardia
• alopecia
• husky voice
• dry skin
• cold intolerance
• clumsiness

• hyperactivity
• osteoporosis
• weight loss
• tachycardia
• tiredness, weakness, SOB#
• goitre

• macrovascular - inc risk of stroke, MI, poor blood flow to the feet
• microvascular - diabetic eye, neuropathy, nephropathy, diabetic feet

excess glucose in peripheral nerves, eyes and kidneys > formation of sorbitol > osmotic damage to cells

HbA1c should be 4-6%

• autoimmune
• affecting B cells in pancreas
• triad of symptoms : polydipsia, polyuria, weightloss
• treat with insulin

• disorder of secretion or resistance
• symptoms: may have triad, tiredness, lack of energy, persistent infections, slow healing, visual problems
• diagnosis = random glucose > 11.1mmol/l or fasting glucose > 7 mmol/l
• management = lifestyle, hypoglycaemia drugs, insulin

• malignant - PTHrp - small cell lung cancer - mimicks PTH
• primary - adenoma, hyperplasia,carcinoma
• secondary - low vit D intake, chronic renal failure
• tertiary - after prolonged secondary

• primary - autoimmune
• secondary - radiation/surgery

• pins and needles
• muscle cramps
• depression
• convulsions
• paralysis
• tetany
• coma

• hypoparathyroidism
• chronic renal failure (raised phosphate)
• osteomalacia
• vit d deficiency

• tetany
• depression
• parathesia
• catarcts

• hyperparathyroidism
• malignacy

• ab pain
• vomitting
• constipation
• polyuria
• polydipsia
• depression
• anorexia
• weight loss
• tiredness
• weakness
• hypertension
• confusion
• pyrexia
• renal stones
• renal failure
• cardiac arrest

• 3 organ systems - bone, kidney, GIT
• 3 hormones - calcitriol, calcitonin, PTH

• structure - often 4, 2 cell types: cheif cells produce PTH and oxyphil cells
• location - posterior thyroid gland