biochem carbohydrate metabolism II

what are the 3 energy generating fuels stored in a 70kg human body

1. carbs (in the form of glycogen; muscle and liver) = <1%

2. fat (triglcerides; in adipose tissue) = 85%

3. protein (muscle protein) = 15%

what is the order of preference fuel usage by tissues in normal physiological conditions

1. carbs

2. fats

3. proteins

why are carbs the most preferred energy source?

- all tissues receive blood; blood contains glucose

- all tissues can metabolize glucose (either aerobically or anerobically)

- more importantly, RBC and brain are dependent on glucose

therefore, glucose is more preferred for energy generation and maintaining basal levels of blood glucose

fats (3)

- can be stored in large amounts in small volume

- fatty acids (energy providing component of fats) can NOT be converted to glucose

- can NOT be metabolized aerobically

proteins (1)

needed for cellular and structural functions

what is the percentage of tissue weight of liver glycogen

5.0 - 10.0

what is the tissue weight of liver glycogen

1.8 kg

what is the body content of liver glycogen

100-150 g

what is the percentage of tissue weight of muscle glycogen

1.0-2.0

what is the tissue weight of muscle glycogen

35 kg

what is the body content of muscle glycogen

250-400 g

what is the percentage of tissue weight of extracellular glucose

0.1

what is the tissue weight of extracellular glucose

10 L

what is the body content of extracellular glycose

10 g

how will the amounts of stored glycogen be altered

form glycogen storage disorders

what is the difference between the storage of glycogen in the muscle and liver

- muscle glycogen is readily available source of glucose for glycolysis within the muscle (ONLY useful for muscles)

liver glycogen stores increase in fed state

- 12-18 hrs of fasting causes complete depletion of liver glycogen

- liver glycogen function is to release glucose in fasting state (between meals) to maintain blood glucose levels to support basal function of tissues

what is the purpose of the extensive branches of glycogen (3)

1. enhances solubility

2. acceleration of synthesis

3. increased sites for degradation

how does branching work and what does it help with

it increases the number of non-reducing sites

- new glucose residues can be added or released rapidly by the enzymes during synthesis and breakdown respectively

where does the synthesis of glycogen (glycogenesis) occur

cytosol

what is needed for the initiation of glycogenesis

preexisting piece of glycogen / primer (also known as a glycogenin)

- a protein with autocatalytic activity that is capable of synthesizing a piece of glycogen

what is the 1st step of glycogenesis

glucose to glucose 6-PO4 to glucose 1-PO4

what catalyzes the reaction of glucose to glucose 6-PO4 (in the liver and in muscle)

liver = glucokinase

muscle = hexokinase

what catalyzes the reaction of glucose 6-PO4 to glucose 1-PO4 (in the liver and in muscle)

phosphoglucomutase

what is the 2nd step of glycogenesis

formation of UDP-glucose

what catalyzes the formation of UDP glucose form glucose 1-PO4

UDP-glucose pyrophosphorylase (UTP ->PPi)

what is the 3rd step of glycogenesis

addition of glucoses for glycogen chain elongation by glycogen synthase (makes alpha 1 -> 4 linkages)

- forms an alpha 1 -> 4 glycosidic bond between UDP glucose and another glucose residue present in preexisting glycogen primer of glycogenin

*glycogen is elongated at non-reducing end by the addition of 8-10 glucoses

what is the 4th step of glycogenesis

formation of branches to extend glycogen structure by branching enzyme 4 -> 6 transferase (makes alpha 1 -> 6 linkages)

- transfer of elongated chain and establishment of new branch point by branching enzyme

- branching involves detachment of a fragment (of 5-6 glucoses) by branching enzyme form non-reducing end of the elongated alpha 1 -> 4 chain and link it to another glucose in the chain or to a neighboring chain by an alpha 1-> 6 linkage

what is glycogenolysis

glycogen degradation to generate glucose

where does glycogenolysis occur

cytosol

what are the primary end products of glycogenolysis (2)

- glucose 1- PO4

- some free glucose released (from each end of an alpha 1-> 6 glucose linkage; the non-reducing end)

what is step 1 of glycogenolysis

shortening of glycogen chains and release of glucose 1-PO4 via glycogen phosphorylase

what is step 2a of glycogenolysis

removal of branches

- removal and transfer of branches by debranching enzyme (4:4 transferase from limit dextrin)

what is step 2b of glycogenolysis

removal of branches

- hydrolysis of alpha 1 ->6 linkages by debranching enzyme alpha 1 -> 6 glucosidase

what is step 3 of glycogenolysis

conversion of glucose 1-PO4 to glucose 6-PO4 by phosphoglycomutase

here is the whole picture

what does the liver do to glycogen in the fed state

stores it

what does the liver do to glycogen in the fasting state

liver glycogen is broken down and glucose released is useful to maintain blood glucose at basal level

is the glucose released from muscle glycogen useful to meet energy needs of the muscle?

yes

is the glucose released from muscle glycogen able to contribute to blood glucose levels?

no

why can't muscle glucose enter the blood to maintain blood glucose at the basal level during fasting

muscle tissue lacks the enzyme glucose-6 phosphotase that is necessary for the conversion of glucose-6 PO4 to glucose

what are the negative allosteric regulators of glycogen metabolism in the liver (3)

1. glucose

2. ATP

3. glucose 6-PO4

what are the positive allosteric regulators of glycogen metabolism in the liver (1)

glucose 6-phosphate

what are the negative allosteric regulators of glycogen metabolism in muscle (2)

1. glucose 6-PO4

2. ATP

what are the positive allosteric regulators of glycogen metabolism in muscle (3)

1. AMP

2. Ca2+

3. glucose 6-PO4

REMEMBER ALL OF THIS

regulation of liver glycolysis in FED state

regulation of liver glycolysis in FASTING state

what are glycogen storage disorders characterized by

deposition of abnormal type of glycogen due to impaired synthesis of

- abnormal quantity of glycogen due to impaired degradation

what is the failure to mobilize glycogen due to

defective enzymes

- hereditary / genetic diseases

- mild and not life threatening but sometimes fatal in infancy

what is glycogen synthase deficiency type 0

elongation of glycogen will NOT occur as new glucose residues are not incorporated due to glycogen synthase deficiency

- hypoglycemic state occurs as glycogen is not available to release glucose

- hyperketonemia = early death

what is Von Gierke's disease (type I)

glycogen accumulates as its degradation is blocked

- severe fasting hypoglycemia as glucose is not released into blood stream

- affects liver and kidney

- hepatomegaly, renomegaly, progressive renal disease, and fatty liver

- hyperlipidemia, hyperlacticacidemia, growth retardation, and delayed puberty

what is Von Gierke's disease (type I) caused by

glucose 6-phosphatase deficiency

is muscle tissue affected in Von Gierke's disease?

no

how to treat Von Gierke's disease

administration of uncooked starch

what is Pompe's disease (type II) caused by

lysosomal alpha 1->4 and alpha 1->6 glucosidase deficiency

what is Pompe's disease (type II)

inborn lisoosmal enzyme defect in liver, heart, and muscle

- accmulation of glycogen in lysosomes

- muscle hypotonia

- massive cardiomegaly due to thickening of heart muscles

- affects pumping of blood; death from heart failure by age 2

how to treat Pompe's disease (type II)

enzyme replacement therapy available

what is Forbe's / Cori disease (type III) caused by

limit dextrinosis; debranching enzyme deficiency

what is Forbe's / Cori disease (type III)

accumulation of characteristic branched glycogen limit dextrin

- fasting hypoglycemia; hepatomegaly in infants

what is McArdle's syndrome (type V) caused by

skeletal muscle glycogen phosphorylase deficiency

what is McArdle's syndrome (type V)

muscle glycogen is abnormally high

- poor exercise tolerance

- temporarily weakness and cramping after exercise

- no rise in blood lactate during strenuous exercise

- myoglobinemia and myoglobinuria

is the liver affected in McArdle's syndrome (type V)

no

what is gluconeogenesis

the process of synthesizing glucose using compounds other than carbohydrates

in normal physiological conditions when glucose is available this pathway plays a (major/minor) role

minor

when does the body turn to gluconeogenesis for energy (3)

1. prolonged fasting

2. starvation

3. diet with insufficient carbohydrates