pathogenesis of metabolic disturbances

• fatty liver

• chicken

• liver gene xoression

• lipid droplets visibke

normal chicken liver with normal sized hepatocytes

causes of liver steatosis

overeating

• normally liver processes dietary fats (chylomicron remnants) and temporary stores some that is later packaged into VLDL and transported to adipose for long term storage

• in persistent overeating the liver pathways for dealing with dietary fat are overwhelmed and liver accumulates excessive amounts of fat

• increase in dietary intake and de novo lipogenesis

starvation

• increase in mobilisation of fat from adipose tissue in response to body energy needs

• if mobilisation exceeds beta oxidation the liver will store the mobilised fatty acids as triglycerides—>fatty change

diabetes

• abnormal carb metabolism results in alternative pathways being utlised for energy production increasing fatty acids and triglycerides increasing fatty change

• increase beta oxidation→increase acetyl coa→ketone body production→ketoacidosis

ruminant production diseases

• demand for glucose and negative energy balance accelerate gluconeogenesis and increase fat mobilisation→increase fatty acid, increase triglyceride, increase glucose

• increase beta oxidation→increase acetyl coa→increase ketone body production→increase ketoacidosis

glycogen storage diseases

• inability to synthesise or degrade glycogen

• result in glycogen accumulation in various tissues depending on the enzyme affected

• most often autosomal recessive although PSSM in horses is autosomal dominant

• all identifiable by genetic testing

• for autosomal recessive GSDs reputable breeders can identify and avoid breeding 2 carriers therefore peventing birth of affected puppies and kittens

branching enzyme deficiency- GSD IV in norwegian forest cats

• caused by autosomal recessive mutation in gene encoding glycogen branching enzyme inhibiting its activity

• results in synthesis of abnormal glycogen that contain longer chain lengths and fewer branch points

• initial signs develop by 5 months of age- muscle tremors, weakness, atrophy

• difficulty chewing dry food and swallowing solid food

• cardiac disease

• causes death in early adulthood

glycogen synthase- polysaccharide storage myopathy in horses

• caused by autosomal dominant mutation in gene encoding glycogen synthase

• mutation causes an upregulation of glycogen synthase

• high levels of glycogen synthase activity direupts the balance of glycogen synthase to glycogen branching enzyme

• results in synthesis of abnormal glycogen that contain longer chain lengths and fewer branch bpoints

• reluctance to move, muscle stiffness, cramping, tremors, tying up due to muscle breakdown during/after exercise

• manageable thorugh careful dietary and exercise adjustment

glycogen debranching enzyme deficiency- GSD III in german shepards

• caused by autosomal recessive mutation in gene encoding debranching enzyme

• results in accumulation of glycogen in liver and muscle

• type iia affects liver and muscle, type iiib primarily affects liver

• hepatomegaly and abdominal distention from excessive glycogen accumulation in liver

• musce weakness and trembling

• exercise intolerance

• hypoglycaemia

• manageable through dietary adjustments to prevent hypoglycaemia

glycogenosis

body cannot make, store or breakdown glycogen due to an enzyme deficiency so abnormal glycogen buildup

examples of enzymes which can be mutated to result in glycogen storage diseases

• glycogen synthase

• branching enzyme

• debranching enzyme

• glucose-6-phosphatase

• phosphofructokinase

role of AGL in glycogenolysis

• codes for debranching enzyme

• ⍺-1,4 transglycosylase activity

• ⍺-1,6 glucosidase activity

glucose-6-phosphatase deficiency- GSDIa

• maltese and other small breeds

• severe hypoglycemia

• hepatomegaly (glycogen cannot be broken down)

• frequent small feedings to maintain blood glucose levels, cornstarch can also manage

phosphofructokinase deficiency-GSD VII

• springer spaniels

• muscle cramps and muscle weakness

• exercise intolerane and rhabdomyolysis

• haemolysis and anaemia

• avoid high intensity strenuous exercise

phosphocreatine system

• rapidly generates ATP from stored PCr in muscles

• only lasts 10 seconds and needs 2-3 mins of rest to fully replenish

• occurs in cytoplasm of muscle cells

• primarily used for short maximal efforts

• can give a boost for surges during endurance efforts

myokinase reaction (adenylate kinase)

• rapidly regenerates ATP from ADP during high energy demands in intensely contracting muscles

• helps provide immediate small amount of ATP to sustain muscle function

• produces AMP as well as ATP

• AMP is an allosteric activator of glycolysis and glycogenolysis